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  1. .gitattributes +5 -0
  2. data/processed/arv_metadata/default__vector_store.json +3 -0
  3. data/processed/arv_metadata/docstore.json +0 -0
  4. data/processed/arv_metadata/graph_store.json +1 -0
  5. data/processed/arv_metadata/image__vector_store.json +1 -0
  6. data/processed/arv_metadata/index_store.json +1 -0
  7. data/processed/arv_metadata/~BROMIUM/default__vector_store.json +0 -0
  8. data/processed/arv_metadata/~BROMIUM/docstore.json +0 -0
  9. data/processed/arv_metadata/~BROMIUM/graph_store.json +0 -0
  10. data/processed/arv_metadata/~BROMIUM/image__vector_store.json +0 -0
  11. data/processed/arv_metadata/~BROMIUM/index_store.json +0 -0
  12. data/processed/disease_vectorstore/index.faiss +3 -0
  13. data/processed/disease_vectorstore/index.pkl +0 -0
  14. data/processed/disease_vectorstore/~BROMIUM/index.faiss +0 -0
  15. data/processed/disease_vectorstore/~BROMIUM/index.pkl +0 -0
  16. data/processed/idsr_keywords.txt +109 -0
  17. data/processed/kenyan_names.txt +135 -0
  18. data/processed/location_data.sqlite +3 -0
  19. data/processed/lp/indices/ARV-PostExposureProphylaxis/default__vector_store.json +1 -0
  20. data/processed/lp/indices/ARV-PostExposureProphylaxis/docstore.json +1 -0
  21. data/processed/lp/indices/ARV-PostExposureProphylaxis/graph_store.json +1 -0
  22. data/processed/lp/indices/ARV-PostExposureProphylaxis/image__vector_store.json +1 -0
  23. data/processed/lp/indices/ARV-PostExposureProphylaxis/index_store.json +1 -0
  24. data/processed/lp/indices/ARV-PostExposureProphylaxis/~BROMIUM/default__vector_store.json +0 -0
  25. data/processed/lp/indices/ARV-PostExposureProphylaxis/~BROMIUM/docstore.json +0 -0
  26. data/processed/lp/indices/ARV-PostExposureProphylaxis/~BROMIUM/graph_store.json +0 -0
  27. data/processed/lp/indices/ARV-PostExposureProphylaxis/~BROMIUM/image__vector_store.json +0 -0
  28. data/processed/lp/indices/ARV-PostExposureProphylaxis/~BROMIUM/index_store.json +0 -0
  29. data/processed/lp/indices/AdherencePreparationMonitoringSupport/default__vector_store.json +0 -0
  30. data/processed/lp/indices/AdherencePreparationMonitoringSupport/docstore.json +0 -0
  31. data/processed/lp/indices/AdherencePreparationMonitoringSupport/graph_store.json +1 -0
  32. data/processed/lp/indices/AdherencePreparationMonitoringSupport/image__vector_store.json +1 -0
  33. data/processed/lp/indices/AdherencePreparationMonitoringSupport/index_store.json +1 -0
  34. data/processed/lp/indices/AdherencePreparationMonitoringSupport/~BROMIUM/default__vector_store.json +0 -0
  35. data/processed/lp/indices/AdherencePreparationMonitoringSupport/~BROMIUM/docstore.json +0 -0
  36. data/processed/lp/indices/AdherencePreparationMonitoringSupport/~BROMIUM/graph_store.json +0 -0
  37. data/processed/lp/indices/AdherencePreparationMonitoringSupport/~BROMIUM/image__vector_store.json +0 -0
  38. data/processed/lp/indices/AdherencePreparationMonitoringSupport/~BROMIUM/index_store.json +0 -0
  39. data/processed/lp/indices/Age-AppropriateDisclosureforChildrenandAdolescents/default__vector_store.json +1 -0
  40. data/processed/lp/indices/Age-AppropriateDisclosureforChildrenandAdolescents/docstore.json +1 -0
  41. data/processed/lp/indices/Age-AppropriateDisclosureforChildrenandAdolescents/graph_store.json +1 -0
  42. data/processed/lp/indices/Age-AppropriateDisclosureforChildrenandAdolescents/image__vector_store.json +1 -0
  43. data/processed/lp/indices/Age-AppropriateDisclosureforChildrenandAdolescents/index_store.json +1 -0
  44. data/processed/lp/indices/Age-AppropriateDisclosureforChildrenandAdolescents/~BROMIUM/default__vector_store.json +0 -0
  45. data/processed/lp/indices/Age-AppropriateDisclosureforChildrenandAdolescents/~BROMIUM/docstore.json +0 -0
  46. data/processed/lp/indices/Age-AppropriateDisclosureforChildrenandAdolescents/~BROMIUM/graph_store.json +0 -0
  47. data/processed/lp/indices/Age-AppropriateDisclosureforChildrenandAdolescents/~BROMIUM/image__vector_store.json +0 -0
  48. data/processed/lp/indices/Age-AppropriateDisclosureforChildrenandAdolescents/~BROMIUM/index_store.json +0 -0
  49. data/processed/lp/indices/AntiretroviralTherapyInfantsChildrenAdolescentsAdults/default__vector_store.json +0 -0
  50. data/processed/lp/indices/AntiretroviralTherapyInfantsChildrenAdolescentsAdults/docstore.json +1 -0
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+ data/processed/lp/summary_embeddings/embeddings.npy filter=lfs diff=lfs merge=lfs -text
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data/processed/arv_metadata/graph_store.json ADDED
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ARVs for Post-exposure Prophylaxis\n\nAn ARV regimen, with preferably three-drugs, should be offered as post exposure prophylaxis as soon as possible (preferably within 72 hours) after an exposure.\n\n## 10.1 What is PEP?\n\nPost-exposure prophylaxis (PEP) is short-term use of antiretroviral treatment to reduce the likelihood of HIV infection after potential exposure.\n\nPeople can be accidentally exposed to HIV through healthcare work or due to exposures outside healthcare setting, for example, through unprotected sex or sexual assault among adults and children. Healthcare workers are at increased risk of exposure to HIV through contact with contaminated blood and other body fluids containing HIV through needle stick injuries and injuries by other sharp objects or through non-intact skin and mucous membranes.\n\n## 10.2 Recommended ARVs for PEP\n\nThree-drug regimens are preferred for PEP. However, if the person is unable to tolerate the third drug, (usually the PI/r), two drugs can be used.\n\n### Table 10.1: Recommended ARVs for PEP\n\n| Age | Weight | Preferred | Alternate |\n| ---------- | ---------- | -------------------- | ----------------------------------------------------------------------- |\n| <15 years | < 30kg | ABC + 3TC + DTG | \u25cf AZT + 3TC + DTG<br/>\u25cf AZT+3TC and LPV/r may be used as the third drug |\n| | \u2265 30 kg | TDF + 3TC /FTC + DTG | \u25cf TDF+3TC/FTC and ATV/r may be used as alternative third drug |\n| \u2265 15 years | Any weight | TDF + 3TC/FTC + DTG | \u25cf TDF+3TC/FTC and ATV/r may be used as alternative third drug |\n\n\n\n\n# 10.3 Eligibility For PEP\n\nPEP should always be offered as soon as possible, preferably within 72 hours, after an exposure. Persons who present after 72 hours should be provided with other appropriate services including counselling and support.\n\nEligibility assessment for PEP is based on the type of exposure, HIV status of source where possible and timing of seeking care.\n\nThe following include the eligibility criteria for PEP.\n\n- Exposed individual is HIV negative at baseline.\n- Exposure must have occurred within the past 72 hours.\n- Exposure to bodily fluids pose a significant risk (exposure and/or material):\n- Type of exposure: mucous membrane (i.e. sexual exposure; splashes to eye, nose, or oral cavity), non-intact skin, percutaneous injury or parenteral exposures\n- Material: blood, blood-stained body fluids, breast milk; semen; vaginal secretions; synovial, pleural, pericardial, amniotic fluids; CSF, and HIV cultures in laboratories\n\nExposures that do not require HIV PEP include:\n\n- When the exposed individual is already HIV positive.\n- Exposures to bodily fluids that do not pose a significant risk, i.e., tears, non-blood-stained saliva, urine, and sweat.\n\n# 10.4 Management and Follow Up\n\nPatients should be counselled and encouraged to complete the full course of PEP once a decision has been made to initiate PEP.\n\nFor occupational exposure, immediate care of the exposure site includes washing the site with soap and water and allow the wound to bleed freely for several minutes.\n\nNOTE: Do not do anything that will increase tissue damage such as squeezing, scrubbing, or cutting the site further.", "mimetype": "text/plain", "start_char_idx": 2, "end_char_idx": 3301, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "933ac606-b019-4eaa-92f0-06b066222507": {"__data__": {"id_": "933ac606-b019-4eaa-92f0-06b066222507", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "92d65265-95de-4544-936d-61b4aec0f81f", "node_type": "4", "metadata": {}, "hash": "cc2d94f6afdef32dacb9366b4aa997655f302c3ca271a25621314f854d663a8f", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "f062b550-0734-44e5-8312-35c1c94e4195", "node_type": "1", "metadata": {}, "hash": "30f3b4451006d9524fe21a92c19b08166ab587bdcda6f806b36e44394f8c187d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Table 10.2: Recommendations for PEP Management and Follow-up\n\n| Considerations | Recommendation |\n| ------------------------------------ | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |\n| Management at initial contact | * Counsel on risks and benefits of PEP and obtain verbal consent for HIV testing.\n* Voluntary testing for both exposed and source individuals\n* Offer PEP as soon as high-risk exposure is established and the exposed individual tests HIV-negative at baseline (if HIV testing not feasible, offer 1-2 days of PEP to cover until HIV test performed)\n* Provide first aid in case of broken skin or other type of wound |\n| Time of initiation | As soon as possible after exposure, but no later than after 72 hours |\n| Duration of PEP | 28 days (dispense all 28 days of treatment at the first visit if tested HIV negative) |\n| Dose of PEP | Same as indicated for treatment; use weight-based dosing for children |\n| Laboratory investigation at baseline | - Conduct creatine testing (if TDF-containing regimen) and Hb (if AZT-containing regimen), however PEP should be offered even when lab tests are not available. Do not delay administration of PEP while waiting for lab results.\n- HBsAg testing is recommended. Do not delay administration of PEP while waiting for lab results. If negative provide HBV vaccination\n- Pregnancy testing for women of childbearing potential in case of sexual assault. |\n| Follow-up | * Follow up client at 7 days, 14 days, 28 days, and 12 weeks after starting PEP\n* Assess for and manage side effects due to PEP\n* Follow-up HIV testing should be done at the completion of PEP and if negative, test again at 12 weeks\n* Link to HIV treatment if positive |\n| Counselling | Counselling at baseline should include:* Adherence counselling\n* Information on side effects\n* Risk reduction counselling\n* Trauma and mental health counselling\n* Specific support for sexual assault |\n| Other services for sexual assault | - STI prophylactic treatment to all (treat for vaginal/urethral discharge syndrome following the national STI algorithms)\n- Emergency contraception for non-pregnant women\n- Tetanus toxoid for any physical injury of skin or mucous membranes\n- Documentation of clinic evidence of assault and collection of forensic evidence |\n\n\n\n\n\n\n## 10.5 Risk reduction counselling\n\nTo reduce the risk of further HIV transmission, it is necessary to prevent transmission to sexual partners and the children of breastfeeding mothers. Risk reduction counselling should form part of each consultation with the individual. Measures to reduce transmission to another person may include:\n\n\u2022 The use of condoms and safe injecting practices to prevent secondary transmission\n\u2022 Avoiding blood donation until confirmed HIV negative at 12 weeks post exposure\n\n### Table 10.3 Considerations for special circumstances\n\n| Circumstance | Recommendation |\n| ------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |\n| Breastfeeding women | \u2022 Breastfeeding is not a contraindication for PEP<br/>\u2022 The risks and benefits of continuing breastfeeding while HIV transmission risk is unknown and should be discussed with the mother |\n| Children | \u2022 HIV testing approaches for children should be in line with national guidelines and age appropriate<br/>\u2022 Informed consent from the caregiver is needed |\n| Adolescents | \u2022 Requiring parental consent for adolescents can be a barrier to HIV testing, particularly in cases of sexual assault<br/>\u2022 HIV testing should be performed in accordance with national guidelines and consenting requirements |\n\n\n## 10.6 Preventing HIV exposure\n\nTo avoid or minimize the risk of exposure to HIV the following infection prevention control (IPC) measures are recommended:\n\n\u2022 Precautions should be taken when handling contaminated body fluids including the use of appropriate barriers such as gloves, gowns, and goggles.\n\u2022 Care with sharps including minimizing blind surgical procedures and proper handling and disposal of sharps.\n\u2022 Safe disposal of contaminated waste\n\u2022 Safe handling of soiled linen.\n\u2022 Adequate disinfection procedures\n\u2022 Universal Hepatitis B vaccination of non-immune at-risk groups including HCWs, police, prison staff and rescue workers.\n\nIn cases that do not require PEP, the exposed person should be counselled about limiting future exposure risk.", "mimetype": "text/plain", "start_char_idx": 3305, "end_char_idx": 10796, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}}, "docstore/metadata": {"f062b550-0734-44e5-8312-35c1c94e4195": {"doc_hash": "30f3b4451006d9524fe21a92c19b08166ab587bdcda6f806b36e44394f8c187d", "ref_doc_id": "92d65265-95de-4544-936d-61b4aec0f81f"}, "933ac606-b019-4eaa-92f0-06b066222507": {"doc_hash": "01f69a43ecd82020638a4eabc7ff71614b9170ad54ce1f1e01016849ef9c83e6", "ref_doc_id": "92d65265-95de-4544-936d-61b4aec0f81f"}}}
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+ {"docstore/ref_doc_info": {"59187269-1f48-4f91-83e0-c51b2f5d67da": {"node_ids": ["10a7ac95-d2fc-4e8f-b857-121d36839b75"], "metadata": {}}}, "docstore/data": {"10a7ac95-d2fc-4e8f-b857-121d36839b75": {"__data__": {"id_": "10a7ac95-d2fc-4e8f-b857-121d36839b75", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "59187269-1f48-4f91-83e0-c51b2f5d67da", "node_type": "4", "metadata": {}, "hash": "95327a6404f6709f8a2ee930442879427859c365090739fc7b99df0250a36ca2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Annex 5: Age-Appropriate Disclosure for Children and Adolescents\n\n| Age Characteristics | Stage of Disclosure | Provider Actions | |\n| ------------------- | ------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |\n| 0 - 4 years | No disclosure | At this stage no disclosure is done since the child is too young to understand about HIV | |\n| 5 - 8 years | Partial disclosure | At this age the child can understand a lot. Define the virus as a germ and the CD4 as the soldier in the body that keeps fighting and one has to take the drugs to strengthen the soldiers in the body | |\n| 9 to 12 years | Full disclosure | Full disclosure is important since most children at this stage are able to understand more about HIV and would have heard about HIV as part of formal education at school | |\n| | | Follow the following stages in the disclosure process<br/><br/>**Stage 1**<br/>Assessing the child's social support system to ensure availability of sufficient support once disclosure is completed<br/><br/>**Stage 2**<br/>Assess the child's prior knowledge about HIV including information given at school, any myths and misconceptions. Offer or reinforce accurate information<br/><br/>**Stage 3**<br/>Use an imaginary exercise or story to assess child's reaction to disclosure of HIV status<br/><br/>**Stage 4**<br/>Tell the child about their HIV status. Support parents to disclose to the child and clarify the mode of infection. Address immediate reactions and concerns a child might have | |\n| | | Post-disclosure<br/>(1-2 weeks after full disclosure) | Find out from the parent/guardian if they have observed anything after disclosure, e.g., change in behavior<br/>\u2022 Introduce the child to tell their story and emerge as a hero (a comic book may be a useful aid)<br/>\u2022 Link the child to a support group or with an older child who has been disclosed to<br/><br/>NB: Find out how the child is doing at every visit after full disclosure |", "mimetype": "text/plain", "start_char_idx": 2, "end_char_idx": 7923, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}}, "docstore/metadata": {"10a7ac95-d2fc-4e8f-b857-121d36839b75": {"doc_hash": "65d978bbdcfd0836fbe75d3396f40b4746bac5970b138c19a1b0293fefca98ef", "ref_doc_id": "59187269-1f48-4f91-83e0-c51b2f5d67da"}}}
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+ {"docstore/ref_doc_info": {"c54f6a50-4346-4cb1-8e6a-e32dd10e2119": {"node_ids": ["578d2aee-7c6e-4369-ae78-9276a7a6e9a6", "c73b2029-bbda-4c95-aad2-520b71807f4c", "c4686376-337b-450c-bf0c-dac37456fed8", "68604d4e-31ae-4565-816f-eeebd5168c88", "7dfd13e4-8e23-4ea0-b7ae-92051a6876e4", "b5a5064d-2cb9-4fcf-a6a3-ae92515e6db5", "71beb4d5-c12e-4261-a1dd-0ca9b1fac06d", "abd77c0d-3ab5-4c35-94dc-f0f7bcb63eb7", "2ed1d236-92b7-4d49-92b4-96370f33532a", "95aedcf0-e1bc-45a6-b3c7-2d6bfa52ab5c", "ac868d7b-34f4-4370-bf1d-4700af6fbb9d", "4b9b4b2f-2623-4e9c-9a37-d3635f1ed7f1", "48ba59fa-ba8a-482a-83ab-d22ecc2e2f5e", "e642316e-72b6-4043-922e-540f5260fb55", "6314e350-d512-413c-850f-35dce0e8b5e4", "bf20c48d-fbb7-4586-8ff7-2504638f92b3", "ecd89dd5-cc4b-4892-bd4a-f401da0092ec", "a4d5323d-c2f4-44df-b88d-33a79585f6cc"], "metadata": {}}}, "docstore/data": {"578d2aee-7c6e-4369-ae78-9276a7a6e9a6": {"__data__": {"id_": "578d2aee-7c6e-4369-ae78-9276a7a6e9a6", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "c73b2029-bbda-4c95-aad2-520b71807f4c", "node_type": "1", "metadata": {}, "hash": "7d0b3340dcf97448ea73fa055738400c6a59960a36870f9bfdd7ecb154cdbf3b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# 6. Antiretroviral Therapy in Infants, Children, Adolescents, and Adults\n\nART, while very effective in managing HIV disease, does not cure HIV infection. The goal of ART is to suppress viral replication with the aim of reducing the patient's VL to undetectable levels. Uninterrupted ART with ongoing strict adherence will help maintain undetectable VL levels thereby preventing damage to the body's immune system, reducing AIDS-related morbidity and mortality and the risk of sexual and vertical transmission of HIV.\n\n## 6.1 Eligibility for ART\n\n| All individuals with confirmed HIV infection are eligible for ART irrespective of CD4 count, WHO clinical stage, age, pregnancy or breastfeeding status, co-infection status, risk group, or any other criteria. |\n| ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |\n\n\n## 6.2 Timing of ART Initiation\n\nART should be started in all patients as soon as possible, preferably within 2 weeks of confirmation of HIV status, and even on the same day as testing positive for HIV if they are ready.\n\nART Readiness Criteria (Table 5.4) can be used to help determine any issues that need to be addressed around the time of ART initiation. Same-day ART initiation (on the same day as testing HIV-positive) has additional benefits for HIV prevention (e.g., for pregnant and breastfeeding women, and the HIV positive partner in a discordant relationship), and is associated with improved retention, viral suppression, and survival. Special considerations for timing of ART initiation are listed in Table 6.1.\n\n\n\n## Table 6.1: Special Considerations for Timing of ART Initiation\n\n| Population | Timing of ART Initiation | Additional Notes |\n| ------------------------------------------------------------ | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------------------------------------------------------------------------------------------------------------- |\n| Pregnant and breastfeeding women | Support ART initiation on the same day as testing positive for HIV | Intensive adherence counselling, support and close follow-up required because of limited time for patient preparation |\n| Infants (< 12 months old) | Support ART initiation on the same day as testing positive for HIV. Treatment should commence following a first positive PCR test. ALWAYS take a sample for a confirmatory PCR test as soon as the first positive PCR result is received, but do not delay ART initiation for the second PCR result | Intensive adherence counselling, support and close follow-up required because of limited time for caregiver preparation |\n| Patients with strong motivation to start ART immediately | Support ART initiation as soon as the patient feels ready, preferably on the same day as testing positive for HIV | Intensive adherence counselling, support and close follow-up required because of limited time for patient preparation |\n| Patients with newly diagnosed TB | Start anti-TB treatment immediately and initiate ART as soon as anti-TB medications are tolerated, preferably within 2 weeks. For TB meningitis delay ART for 4 to 8 weeks | Monitor closely for IRIS (Annex 16) |\n| Patients with cryptococcal meningitis | Defer ART until after completing 5 weeks of CM treatment | Monitor closely for IRIS (Annex 16) |\n| Patients for whom adherence will be particularly challenging | Start ART as soon as possible while implementing additional support systems (e.g., optional enrolment of a PWID into a MAT program; psychiatric treatment for a patient with mental illness; enrolment into an OVC program for orphans etc.) | A case manager should be assigned to all patients with complex adherence challenges |\n| All other patients | Start ART as soon as possible, preferably within 2 weeks, and even on the same day as testing positive for HIV if they are ready | Continued adherence monitoring and support is recommended after ART initiation for all patients |", "mimetype": "text/plain", "start_char_idx": 2, "end_char_idx": 6101, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c73b2029-bbda-4c95-aad2-520b71807f4c": {"__data__": {"id_": "c73b2029-bbda-4c95-aad2-520b71807f4c", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "578d2aee-7c6e-4369-ae78-9276a7a6e9a6", "node_type": "1", "metadata": {}, "hash": "909fe5c6ecb57ef45ea9db56e1b5328c905525ab2418dcc77d625132b2f49803", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "c4686376-337b-450c-bf0c-dac37456fed8", "node_type": "1", "metadata": {}, "hash": "0b3cd37fdc78e00b34c7206309d765f631818f984c7dddb45426a5af90433a3e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Antiretroviral Therapy in Infants, Children, Adolescents, and Adults\n\n## 6.3 First-Line ART for Infants, Children, Adolescents and Adults (including Pregnant and Breastfeeding Women)\n\nThe recommendations below apply to patients who are starting ART for the first time. Preferred and alternative first line regimens are shown in Tables 6.2 and 6.3. ARVs for infant prophylaxis are presented in the PMTCT chapter in Tables 7.3 to 7.6.\n\n**All patients must have their weight documented at every visit. Children and adolescents less than 15 years must have correct weight-based dosing of ARVs confirmed at every visit.**\n\nInfants and children depend on their caregivers for adherence to medication. Caregivers should be adequately prepared for their role of administering ARVs to infants and children, including addressing anticipated challenges such as drug palatability. It can be helpful for more than one caregiver to be informed about a child's HIV status and receive instruction on administration of ART.\n\n**Caregivers should always be shown and then asked to demonstrate how to measure and administer ARVs. This should be done both at the time of prescribing the ART (by the clinician) and at the time of dispensing the ART. Clinicians should ensure that the caregiver accompanying a child for clinical review is the same caregiver responsible for day-to-day ART administration.**\n\n### Table 6.2: Preferred First-line ART Regimens and Dosing for Children, Adolescents and Adults<sup>1</sup>\n\n| Age | Weight | Preferred Regimen | Dosing (correct weight-based dosing must be confirmed at every visit) |\n| ----------------------- | ------- | ------------------ | --------------------------------------------------------------------- |\n| Birth to 4 weeks | Any | AZT + 3TC + NVP3 | Refer to Annex 10 for weight-based dosing |\n| > 4 weeks to < 15 years | < 30 kg | ABC + 3TC + DTG4 | Refer to Annex 10 for weight-based dosing |\n| | \u2265 30 kg | TDF + 3TC + DTG5,6 | TDF/3TC/DTG (300/300/50mg): 1 tab once daily |\n| \u2265 15 years | Any | TDF + 3TC + DTG5,6 | TDF/3TC/DTG (300/300/50mg): 1 tab once daily |\n\n\n1. Patients currently on first-line regimens that are not included in the indicated preferred (Table 6.2) or alternative (Table 6.3) regimens should be considered for regimen optimization as per Section 6.5.1\n2. See Annex 10 for weight-based dosing of all single-drug and fixed-dose combination formulations\n3. Infants who initiate ART at less than 4 weeks of age should initiate on AZT+3TC+NVP irrespective of previous ART exposure; metabolism of other ARVs is not well known for this age group. As soon as these infants become 4 weeks old, they should switch to ABC/3TC+DTG (dosing included in Annex 10). Consult the Regional or National HIV Clinical TWG (Uliza Hotline 0726 460 000, ulizanascop@gmail.com) in case of pre-term infants\n4. Once adolescents reach 30 kg, if virally suppressed they should be considered for transition as per Figure 6.2\n5. TAF may become the preferred NRTI once fixed-dose combinations are available\n6. DTG/3TC dual therapy may be considered for HBV-negative patients once fixed-dose combinations are available", "mimetype": "text/plain", "start_char_idx": 6108, "end_char_idx": 9434, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c4686376-337b-450c-bf0c-dac37456fed8": {"__data__": {"id_": "c4686376-337b-450c-bf0c-dac37456fed8", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "c73b2029-bbda-4c95-aad2-520b71807f4c", "node_type": "1", "metadata": {}, "hash": "7d0b3340dcf97448ea73fa055738400c6a59960a36870f9bfdd7ecb154cdbf3b", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "68604d4e-31ae-4565-816f-eeebd5168c88", "node_type": "1", "metadata": {}, "hash": "b8a03d2ed2a6301ef2f727f74cccea3b757a4c3143dddc61cd0d21a3aff170ee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Table 6.3: Use of Alternative ARVs in First-Line Regimens \u00b9\n\n| Age | Weight | Scenario and ARV Affected | Alternative ARV to Use |\n| ----------------------- | ------- | ----------------------------------------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |\n| Birth to 4 weeks | Any | NVP: Develops hypersensitivity reaction | Use RAL granules or LPV/r granules (over 2 weeks of age) or defer ART until 4 weeks of age, then start ABC+3TC+DTG |\n| | | AZT: Infant Hb < 9.5 g/dL | Defer ART until 4 weeks of age, then start ABC+3TC+DTG |\n| > 4 weeks to < 15 years | Any | ABC: Develops ABC hypersensitivity reaction\u00b2 | Use AZT (if Hb \u2265 9.5 g/dL); if Hb < 9.5 g/dL consults Regional or National HIV Clinical TWG (call Uliza Hotline 0726 460 000; ulizanascop\\@gmail.com) |\n| | < 30 kg | DTG: Unable to tolerate | Use LPV/r at standard weight-based BD dosing, if 4-in-1 available this is preferred |\n| | | DTG: Currently on rifampicin-containing anti-TB medications | Increase DTG dosing frequency to twice daily for duration of rifampicin-containing TB treatment and for an additional 2 weeks after TB treatment is completed, then revert to once daily dosing\u00b3 |\n| | \u2265 30 kg | TDF: Impaired renal function (CrCl \u2264 50 ml/min) | Use ABC\u2074,\u2075 or TAF (once available) |\n| | | DTG: Unable to tolerate | Use EFV (for PWID use ATV/r) |\n| \u2265 30 kg | Any | DTG: Currently on rifampicin-containing anti-TB medications | Give TDF/3TC/DTG FDC morning + DTG 50mg evening for duration of rifampicin-containing TB treatment and for an additional 2 weeks after TB treatment is completed, then revert to TDF/3TC/DTG FDC OD \u00b3 |\n| | | TDF: Impaired renal function (CrCl \u2264 50 ml/min) | Use ABC\u2074,\u2075 or TAF (once available) |\n| \u2265 15 years | Any | DTG: Unable to tolerate | Use EFV (for PWID use ATV/r) |\n| | | DTG: Currently on rifampicin-containing anti-TB medications | Give TDF/3TC/DTG FDC morning + DTG 50mg evening for duration of rifampicin-containing TB treatment and for an additional 2 weeks after TB treatment is completed, then revert to TDF/3TC/DTG FDC OD \u00b3 |", "mimetype": "text/plain", "start_char_idx": 9438, "end_char_idx": 13401, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "68604d4e-31ae-4565-816f-eeebd5168c88": {"__data__": {"id_": "68604d4e-31ae-4565-816f-eeebd5168c88", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "c4686376-337b-450c-bf0c-dac37456fed8", "node_type": "1", "metadata": {}, "hash": "0b3cd37fdc78e00b34c7206309d765f631818f984c7dddb45426a5af90433a3e", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "7dfd13e4-8e23-4ea0-b7ae-92051a6876e4", "node_type": "1", "metadata": {}, "hash": "4688d8e48b8f1cca14bd860a0655592acb1711ba80fc75be3e9289c439db9af5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# 6.4 Dosing and Administration of Dolutegravir (DTG)\n\nDTG is preferred in first line ART (in combination with other ARVs) for children, adolescents and adults. DTG is well tolerated, highly efficacious, has a high genetic barrier to resistance and fewer drug-drug interactions.\n\nRecommended Dosing of DTG\n\u25cf &#x3C; 20 kg body weight: Use weight-based dosing with dispersible 10mg DTG tablets as per Annex 10\n\u25cf \u2265 20 kg body weight: DTG 50 mg film-coated tablet once daily, preferably as a morning dose. It is also available as part of FDC. Those unable to swallow the film coated tablets whole refer to Annex 10\n\u25cf For patients taking rifampicin: Increase DTG dosing frequency to twice daily for duration of rifampicin-containing TB treatment and for an additional 2 weeks after TB treatment is completed, then revert to once daily. (The additional 2 weeks of higher-dose DTG is to counter the ongoing liver enzyme induction effect of rifampicin, which continues for a short period after TB treatment is completed)\n\u25cf For patients with suspected or confirmed INSTI resistance (e.g., patients with prior history of failing a RAL-based regimen): use DTG twice daily\n\u25cf DTG can be taken with or without food\n\n# Common Side Effects of DTG\n\n- The most common side effects of DTG are headache, nausea and diarrhea. These side effects usually resolve after continued use for 1-2 weeks. It is critical to inform patients / caregivers about these potential side effects and their temporary nature, and encourage them to continue their ART and consult a HCW if concerned.\n- Some patients on DTG are more likely to develop insomnia. This may be reduced by taking DTG as a morning dose, or by taking DTG with a low-fat meal or on an empty stomach.\n- DTG may cause a small rise in serum creatinine levels but this does NOT represent a true decline in renal function.\n- Integrase inhibitors, including DTG, are associated with increased weight gain. Counsel patients about healthy eating and physical activity and the benefits of maintaining a healthy weight.\n\n1 For other scenarios that are not covered in this table, discuss as an MDT and consult the Regional or National HIV Clinical TWG (Uliza Hotline 0726 460 000; https://nhcsc.nascop.org/clinicalform)\n\n2 ABC hypersensitivity reaction (AHR) is rare in the Kenyan population. Table 6.9 provides the definition and management of AHR\n\n3 The additional 2 weeks of higher-dose DTG is to counter the ongoing liver enzyme induction effect of rifampicin, which continues for a short period after TB treatment is completed\n\n4 TAF may become the preferred NRTI once fixed-dose combinations are available\n\n5 DTG/3TC dual therapy may be considered for HBV-negative patients once fixed-dose combinations are available", "mimetype": "text/plain", "start_char_idx": 13408, "end_char_idx": 16151, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7dfd13e4-8e23-4ea0-b7ae-92051a6876e4": {"__data__": {"id_": "7dfd13e4-8e23-4ea0-b7ae-92051a6876e4", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "68604d4e-31ae-4565-816f-eeebd5168c88", "node_type": "1", "metadata": {}, "hash": "b8a03d2ed2a6301ef2f727f74cccea3b757a4c3143dddc61cd0d21a3aff170ee", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "b5a5064d-2cb9-4fcf-a6a3-ae92515e6db5", "node_type": "1", "metadata": {}, "hash": "a5939500d19350858b5c4443ab2b24a0cd0c98aaaa377e5dea10a797c4592418", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Table 6.4 Cont.\n\n# Pregnancy Safety of DTG\n\n- DTG is safe during pregnancy and breastfeeding. Pregnancy intention should be discussed with all women initiating ART regardless of regimen. Women who do not wish to become pregnant should be offered appropriate family planning counseling and methods.\n\n# Important Drug Interactions with DTG\n\n- Rifampicin\n- Rifampicin lowers DTG levels: increase DTG to 50 mg twice daily for patients on rifampicin who are > 20 kg in body weight. Children &#x3C;20 kg taking DTG who require rifampicin should increase their weight-appropriate DTG dose to twice daily.\n- There are no significant drug interactions between DTG and other currently used anti-TB medications (including for MDR-TB).\n- Mineral supplements, including: antacids containing calcium, zinc, magnesium or aluminum; iron supplements; prenatal vitamins (which contain iron and calcium)\n- These supplements decrease the absorption of DTG: administer DTG at least 2 hours before or 6 hours after taking any of these supplements.\n- Dose separation is not required for calcium and iron supplements (including prenatal vitamins) if DTG is taken with a meal.\n- It is critical to educate patients about this important drug interaction because many patients get these supplements and antacids over-the-counter without informing their healthcare provider.\n- Carbamazepine, phenobarbital, phenytoin\n- These anticonvulsants decrease DTG levels: use a different anticonvulsant if available.\n- If DTG must be co-administered with these drugs then increase to DTG to twice daily, although there is little data to guide this.\n- If valproic acid is available this can be used with DTG without dose adjustment.\n- Metformin\n- DTG increases levels of metformin; the levels of DTG are not affected: use a lower dose of metformin (often 50% of usual dose) and monitor glycemic control. Use a maximum daily dose of metformin 1 g.\n- Other drug-drug interactions with DTG\n- See Annex 13C.\n\n\n\n# 6.5 Monitoring and Changing ART\n\nThe objectives of clinical and laboratory monitoring during ART are to identify and treat inter-current illnesses, assess for and manage adverse drug reactions, and evaluate response to treatment. Routine laboratory monitoring recommendations are described in Table 3.5; however, additional investigations should be ordered whenever there is clinical suspicion for which a laboratory test result may alter patient management.\n\nIndications for changing ART include optimizing therapy for patients who have undetectable viral load, managing adverse drug reactions or toxicity, drug-drug interactions, co-morbidities and treatment failure.\n\n# 6.5.1 Optimizing Therapy for Patients who have suppressed viral load on First Line ART\n\nPatients who are virally suppressed on first line ART may benefit from regimen optimization even if they are currently tolerating their regimen well and have no drug-drug interactions requiring a change. Regimen modifications may be done for age/weight transitions among children and adolescents &#x3C;15 years and to simplify a regimen, prevent long-term toxicity and improve cost-effectiveness. Dolutegravir has been shown to have superior tolerability and efficacy compared to efavirenz and lopinavir and is now preferred as part of first line ART for children, adolescents and adults. While most adults in Kenya have switched over to a DTG-containing regimen, proactive switching of children is now also recommended with the availability of a pediatric dispersible dolutegravir tablet.\n\nChildren and adolescents with suppressed viral load on first line ART and not on the recommended first line regimen as per Table 6.2 should be considered for optimization as per Figures 6.1 and 6.2, such as when children grow and enter a new weight band. This also includes PLHIV who recently initiated non-standard therapy (less than 3 months ago, before the first VL is due). Decisions on regimen modification should be made following discussion with the patient/caregiver.\n\nAlways discuss the possibility of new side effects when changing to a new ARV, particularly side effects common to all ARVs (headache, nausea, diarrhea) and any side effects specific to the new ARV. Reassure patients that most side effects resolve with continued use after 1-2 weeks.", "mimetype": "text/plain", "start_char_idx": 16156, "end_char_idx": 20439, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b5a5064d-2cb9-4fcf-a6a3-ae92515e6db5": {"__data__": {"id_": "b5a5064d-2cb9-4fcf-a6a3-ae92515e6db5", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "7dfd13e4-8e23-4ea0-b7ae-92051a6876e4", "node_type": "1", "metadata": {}, "hash": "4688d8e48b8f1cca14bd860a0655592acb1711ba80fc75be3e9289c439db9af5", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "71beb4d5-c12e-4261-a1dd-0ca9b1fac06d", "node_type": "1", "metadata": {}, "hash": "72fb58b97c31e078ecdec1dff358155eb5bcba28f984761cd5b8af3c4b8e96b5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```mermaid\ngraph TD\n A[Children weighing < 30 kg on a first line ART regimen OTHER than ABC/3TC + DTG]\n B[On ART for < 3 months]\n C[On ART for \u2265 3 months]\n D[VL within last 6 months < 200 copies/ml (LDL)]\n E[No VL result within last 6 months]\n F[VL within last 6 months \u2265 200 copies/ml]\n G[Collect sample for VL]\n H[VL < 200 copies/ml (LDL)]\n I[VL \u2265 200 copies/ml]\n J[Switch to ABC/3TC + DTG using the weight-based dosing from Annex 10A-B<br>Schedule clinical appointment at 2 weeks after regimen change to review adherence, side effects and any other concerns<br>Repeat VL 3 months after regimen modification followed by routine viral load monitoring]\n K[Switch regimen while assessing for reasons for viremia and providing enhanced adherence counselling<br>\u2022 If current regimen contains ABC: Switch to AZT/3TC + DTG<br>\u2022 If current regimen contains AZT: Switch to ABC/3TC + DTG<br>Use the weight-based dosing from Annex 10A-B<br>For all patients on PI/r or DTG containing regimens: summarize case for TWG and take sample for DRT \u2013 do not wait for DRT results for making the regimen modification<br>Schedule clinical appointment at 2 weeks after regimen change to review adherence, side effects and any other concerns<br>Repeat VL 3 months after regimen modification<br>\u2022 If VL still \u2265 200 copies/ml then consult the regional or national TWG<br>\u2022 If VL now < 200 copies/ml then continue routine viral load monitoring]\n\n A --> B\n A --> C\n B --> D\n C --> D\n C --> E\n C --> F\n E --> G\n G --> H\n G --> I\n D --> J\n H --> J\n F --> K\n I --> K\n```\n\nFigure 6.1: Optimizing ART Regimens for Children and adolescents <15 years Weighing < 30 kg on First Line ART", "mimetype": "text/plain", "start_char_idx": 20443, "end_char_idx": 22166, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "71beb4d5-c12e-4261-a1dd-0ca9b1fac06d": {"__data__": {"id_": "71beb4d5-c12e-4261-a1dd-0ca9b1fac06d", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "b5a5064d-2cb9-4fcf-a6a3-ae92515e6db5", "node_type": "1", "metadata": {}, "hash": "a5939500d19350858b5c4443ab2b24a0cd0c98aaaa377e5dea10a797c4592418", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "abd77c0d-3ab5-4c35-94dc-f0f7bcb63eb7", "node_type": "1", "metadata": {}, "hash": "c25c2e7549fab1d5313f857e494fc7ab272a98c07699ea820eaa4cf136718219", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Antiretroviral Therapy in Infants, Children, Adolescents, and Adults\n\n```mermaid\ngraph TD\n A[Children and adolescents weighing \u2265 30 kg or \u2265 15 years old on a first line ART regimen OTHER than TDF/3TC/DTG]\n B[On ART for < 3 months]\n C[On ART for \u2265 3 months]\n D[VL within last 6 months < 200 copies/ml LDL]\n E[No VL result within last 6 months]\n F[VL within last 6 months \u2265 200 copies/ml]\n G[Collect sample for VL]\n H[VL < 200 copies/ml LDL]\n I[VL \u2265 200 copies/ml]\n J[Switch to TDF/3TC/DTG 300/300/50mg 1 tab once daily<br>Schedule clinical appointment at 2 weeks<br>after regimen change to review<br>adherence, side effects and any other<br>concerns<br>Repeat VL 3 months after regimen<br>modification followed by routine viral<br>load monitoring]\n K[Switch regimen while assessing for reasons for viremia<br>and providing enhanced adherence counselling<br>Switch to TDF/3TC/DTG 300/300/50mg 1 tab once<br>daily<br>For all patients on PI/r or DTG containing regimens:<br>summarize case for TWG and take sample for DRT \u2013 do<br>not wait for DRT results for making the regimen<br>modification<br>Schedule clinical appointment at 2 weeks after regimen<br>change to review adherence, side effects and any other<br>concerns<br>Repeat VL 3 months after regimen modification<br>\u2022 If VL still \u2265 200 copies/ml then consult the<br>regional or national TWG<br>\u2022 If VL now < 200 copies/ml then continue routine<br>viral load monitoring]\n A --> B\n A --> C\n C --> D\n C --> E\n C --> F\n E --> G\n G --> H\n G --> I\n B --> J\n D --> J\n H --> J\n F --> K\n I --> K\n```\n\nFigure 6.2: Optimizing ART Regimens for Children and Adolescents Weighing \u2265 30 kg or \u2265 15 years old on First Line ART\n\n## 6.5.2 Changing ARVs Due to Adverse Drug Reactions\n\nPatients starting ART should be educated on the potential side effects of ART and all other prescribed medication. ADRs can have a significant impact on patient adherence and must be identified early and managed aggressively. All ADRs should be reported to the Pharmacy and Poisons Board using existing pharmacovigilance tools (http://www.pv.pharmacyboardkenya.org/). Pharmacovigilance is particularly important for monitoring ADRs associated with any new ARVs that enter the national supply chain, as rare ADRs may appear in routine care, which were not observed in the highly selected patients participating in clinical trials.\n\nThe most common significant ADRs associated with ARVs that may require a drug substitution", "mimetype": "text/plain", "start_char_idx": 22170, "end_char_idx": 24683, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "abd77c0d-3ab5-4c35-94dc-f0f7bcb63eb7": {"__data__": {"id_": "abd77c0d-3ab5-4c35-94dc-f0f7bcb63eb7", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "71beb4d5-c12e-4261-a1dd-0ca9b1fac06d", "node_type": "1", "metadata": {}, "hash": "72fb58b97c31e078ecdec1dff358155eb5bcba28f984761cd5b8af3c4b8e96b5", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "2ed1d236-92b7-4d49-92b4-96370f33532a", "node_type": "1", "metadata": {}, "hash": "e6dfb75107b93af1a0ffe358f6db221aead2eeca5734f04af7453b4ce041639e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Table 6.5: Common Significant Adverse Drug Reactions\n\n| ARV Agent | Adverse Drug Reaction | High Risk Situations/Comments |\n| ------------------------ | --------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |\n| **NRTIs** | | |\n| ABC | ABC hypersensitivity reaction (see Table 6.9) | Do not re-challenge |\n| | Anaemia, neutropenia (See Table 6.7) | Risk factors: CD4 count < 200 cells/mm3; BMI < 18.5 (or body weight < 50 kg); anaemia at baseline; concurrent use of other drugs with similar ADR (cotrimoxazole, gancyclovir, ribavirin) |\n| AZT | | |\n| | Lactic acidosis | Risk factors: Pregnancy; obesity |\n| | Lipoatrophy | Risk factors: Low CD4 count |\n| TDF | Renal dysfunction (See Figure 6.5) | Risk factors: Underlying renal disease; age > 60 years; BMI < 18.5 (or body weight < 50 kg); diabetes; hypertension; concomitant PI use or nephrotoxic drug<br/>Avoid in patients with CrCl< 50ml/minute unless no suitable alternative such as required to treat HIV/HBV co-infection if TAF is not available |\n| TAF | Weight gain | Risk factors: women; concomitant use of INSTIs<br/>Provide advice on healthy eating and physical activity to maintain a healthy weight (Table 4.9) |\n| **NNRTIs** | | |\n| All NNRTIs | Rash (NVP>>EFV>ETR) | Manage rash as per Table 4.4 |\n| EFV | CNS side-effects | Risk factors: Pre-existing psychiatric disorder |\n| | Gynaecomastia | Switch from EFV to an alternative, and consult if gynecomastia does not improve |\n| NVP | Hepatotoxicity (See Table 6.8) | N/A. |\n| **PIs** | | |\n| All PIs boosted with RTV | GI intolerance (LPV/r>DRV/r>ATV/r) | Consult for recommendation on alternative regimen (R-TWG or Uliza Hotline 0726 460 000, https\\://nhcsc.nascop.org/clinicalform) |\n| | Dyslipidaemia (LPV/r>DRV/r>ATV/r) | Risk factors: Obesity; sedentary lifestyle; diet high in saturated fats and cholesterol |\n| ATV/r | Hyperbilirubinemia | This only requires drug substitution if cosmetic effect of jaundice is likely to interfere with patient adherence |\n| DRV/r | Rash/hypersensitivity | Risk factors: sulfa allergy |\n| **INSTIs** | | |\n| All INSTIs | Weight gain | Risk factors: women; concomitant use of TAF<br/>Provide advice on healthy eating and physical activity to maintain a healthy weight |\n| | Rash/hypersensitivity | Consult (Uliza Hotline 0726 460 000, https\\://nhcsc.nascop.org/clinicalform) |", "mimetype": "text/plain", "start_char_idx": 24687, "end_char_idx": 33529, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2ed1d236-92b7-4d49-92b4-96370f33532a": {"__data__": {"id_": "2ed1d236-92b7-4d49-92b4-96370f33532a", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "abd77c0d-3ab5-4c35-94dc-f0f7bcb63eb7", "node_type": "1", "metadata": {}, "hash": "c25c2e7549fab1d5313f857e494fc7ab272a98c07699ea820eaa4cf136718219", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "95aedcf0-e1bc-45a6-b3c7-2d6bfa52ab5c", "node_type": "1", "metadata": {}, "hash": "1d8c804c27a910950a6d30ca53b3e4a87fd06d4a3c989a37c2f235049e1caa94", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Antiretroviral Therapy in Infants, Children, Adolescents, and Adults\n\nAlternative explanations for toxicity must be excluded before concluding a reaction is secondary to an ARV. Consider other medications and herbal remedies and diseases including opportunistic infections, immune reconstitution inflammatory syndrome (IRIS), or other illnesses\n\n```mermaid\ngraph TD\n A[1. Patient/caregiver reports possible adverse event] --> B[History or clinical assessment suggest adverse event]\n B --> C[Lab tests indicate possible problem related to ART]\n A --> D[2. Evaluate concurrent medications & any concurrent new or pre-existing condition Establish whether adverse event is due to:]\n B --> D\n C --> D\n D --> E[other drugs or drug-drug interaction]\n D --> F[other medical condition]\n D --> G[Inter-current illness or IRIS]\n D --> H[Adverse Drug Reaction identified]\n D --> I[Presentation due to other medical condition]\n H --> J[3. Determine seriousness of adverse event]\n I --> K[Manage condition, continue ART]\n J --> L[Life-threatening Grade 4]\n J --> M[Severe Grade 3]\n J --> N[Moderate Grade 2]\n J --> O[Mild Grade 1]\n L --> P[Immediately discontinue ALL drugs, including ARVs and manage the medical event. The patient often requires hospitalization When the patient is stabilised, reintroduce ARVs using a modified regimen substitute the offending drug*]\n M --> Q[Substitute the offending drug without discontinuing ART*. Monitor the patient closely]\n N --> R[Continue ARVs as long as feasible, offer symptomatic relief if appropriate. If no improvement consider single drug substitution*]\n O --> S[Continue ARVs, offer symptomatic relief if appropriate]\n```\n\nPatients identified with ADR, review the patient progress at every clinic visit and document their outcomes\nReport suspected/confirmed adverse drug events by filling the Pharmacovigilance form or online at www.pv.pharmacykenya.org\n\n1. At every clinic visit the patient on ART should be monitored clinically for toxicities using appropriate history (history of symptoms that suggest toxicity) and physical examination (relevant signs). Patients should be asked specifically about ADR known to be associated with their current ART. Targeted laboratory assessment may be used to confirm specific toxicities.\n2. Evaluate concurrent medications and establish whether the toxicity is attributable to an ARV, or to a non-ARV medication taken at the same time. Consider other disease processes (e.g. concurrent infectious processes or IRIS)\n3. All toxicities should be graded. Manage the adverse event according to severity\n\n\\* Follow single-drug substitution algorithm (Figure 6.4)", "mimetype": "text/plain", "start_char_idx": 33536, "end_char_idx": 36232, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "95aedcf0-e1bc-45a6-b3c7-2d6bfa52ab5c": {"__data__": {"id_": "95aedcf0-e1bc-45a6-b3c7-2d6bfa52ab5c", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "2ed1d236-92b7-4d49-92b4-96370f33532a", "node_type": "1", "metadata": {}, "hash": "e6dfb75107b93af1a0ffe358f6db221aead2eeca5734f04af7453b4ce041639e", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "ac868d7b-34f4-4370-bf1d-4700af6fbb9d", "node_type": "1", "metadata": {}, "hash": "aca58b52c8cbdaa96aae50bb843c528d165fccb87447aab0a90f47567f477ba2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```mermaid\ngraph TD\n A[Patients with specific reason for stopping an ARV \u00b9]\n B[On ART for < 3 months]\n C[On ART for \u2265 3 months]\n D[VL within last 6 months < 200 copies/ml]\n E[No VL result within last 6 months \u00b9]\n F[VL within last 6 months \u2265 200 copies/ml]\n G[Collect sample for VL]\n H[VL < 200 copies/ml]\n I[VL \u2265 200 copies/ml]\n J[\"\u2022 Do NOT change the current regimen unless immediate change required for clinical reasons\u00b9<br>\u2022 Follow viral load monitoring algorithm (Figure 6.6)\"]\n K[\"\u2022 Proceed with single drug substitution<br>\u2022 Schedule clinical appointment at 2 weeks after regimen change to review adherence, side effects and any other concerns<br>\u2022 Repeat VL 3 months after regimen modification followed by routine viral load monitoring\"]\n\n A --> B\n A --> C\n A --> F\n B --> D\n C --> E\n E --> G\n G --> H\n G --> I\n D --> K\n H --> K\n I --> J\n F --> J\n\n style A fill:#f9f,stroke:#333,stroke-width:2px\n style B fill:#fcf,stroke:#333,stroke-width:2px\n style C fill:#fcf,stroke:#333,stroke-width:2px\n style D fill:#fcf,stroke:#333,stroke-width:2px\n style E fill:#fcf,stroke:#333,stroke-width:2px\n style F fill:#fcf,stroke:#333,stroke-width:2px\n style G fill:#fcf,stroke:#333,stroke-width:2px\n style H fill:#fcf,stroke:#333,stroke-width:2px\n style I fill:#fcf,stroke:#333,stroke-width:2px\n style J fill:#fcf,stroke:#333,stroke-width:2px\n style K fill:#fcf,stroke:#333,stroke-width:2px\n```\n\n\u00b9 If an ARV must be changed for clinical reasons (adverse drug reaction; drug-drug interaction; co-morbidity; etc) before viral load results available, Urgently consult Uliza Hotline (0726 460 000) or Regional or National TWG\n\nFigure 6.4: Managing Single Drug Substitutions for ART", "mimetype": "text/plain", "start_char_idx": 36236, "end_char_idx": 38007, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ac868d7b-34f4-4370-bf1d-4700af6fbb9d": {"__data__": {"id_": "ac868d7b-34f4-4370-bf1d-4700af6fbb9d", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "95aedcf0-e1bc-45a6-b3c7-2d6bfa52ab5c", "node_type": "1", "metadata": {}, "hash": "1d8c804c27a910950a6d30ca53b3e4a87fd06d4a3c989a37c2f235049e1caa94", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "4b9b4b2f-2623-4e9c-9a37-d3635f1ed7f1", "node_type": "1", "metadata": {}, "hash": "651d36d992c40f6fb40ff2827f57153094347935ffd71725963d43e2e290dc11", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Antiretroviral Therapy in Infants, Children, Adolescents, and Adults\n\n```mermaid\ngraph TD\n A[At every clinic visit, assess for risk of kidney disease:<br>\u2022 Age > 60 years<br>\u2022 Concurrent HIV associated diseases such as TB and other OIs<br>\u2022 Concurrent diabetes, hypertension, viral hepatitis<br>\u2022 Concomitant use of nephrotoxic drugs e.g. aminoglycosides,<br> amphotericin and boosted PIs<br>\u2022 Wasting, low BMI<br>\u2022 CD4 count < 200 cells/mm3] --> B[If any risk factor present]\n B --> C[Obtain a dip stick urinalysis and serum creatinine and calculate<br>creatinine clearance CrCl in ml/min, see Annex 15\u00b9]\n C --> D[\u00b2CrCl \u2265 90<br>TDF 300 mg OD: re-<br>assess creatinine and CrCl<br>at 1 month, 3 months and<br>bi-annually thereafter if<br>normal]\n C --> E[\u00b3CrCl = 50-89<br>TDF 300 mg OD, monitor<br>more closely for decline in<br>renal function monthly<br>during the first year, and 3<br>monthly thereafter if CrCl<br>remains stable]\n C --> F[\u2074,\u2075CrCl = 30-49<br>AVOID: if there is no<br>suitable alternative; give<br>TDF 300 mg every 48<br>hours, monitor closely<br>with monthly CrCl for the<br>first year, and 3 monthly<br>thereafter if stable]\n C --> G[\u2074,\u2075CrCl \u2264 29<br>AVOID: if there is no<br>suitable alternative; give<br>TDF 300 mg every 72<br>hours, monitor CrCl<br>monthly]\n```\n\n\u00b9 DTG may cause a small rise in serum creatinine levels but this does NOT represent a true decline in renal function\n\u00b2 Obtain biannual serum Cr and CrCl in patients at risk of renal disease and a CrCl \u2265 90 ml/min\n\u00b3 Patients with a CrCl \u2265 50 ml/min do not require TDF dose adjustment.\n\u2074 Avoid the use of TDF in patients with CrCl < 50ml/min unless in HIV/HBV coinfection (in which case TAF or TDF should be used). If HBV negative and on first line ART, substitute TDF with ABC, TAF or DTG + 3TC dual therapy. If prior ART treatment failure or any other scenario consult the Regional or National HIV Clinical TWG (Uliza Hotline 0726 460 000).\n\u2075 3TC also requires dose adjustment once CrCl < 50 ml/min\n* For patients with decreased renal function, assess for other causes of renal impairment and refer to physician for review\n\nFigure 6.5: Managing TDF-Associated Kidney Toxicity", "mimetype": "text/plain", "start_char_idx": 38011, "end_char_idx": 40192, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b9b4b2f-2623-4e9c-9a37-d3635f1ed7f1": {"__data__": {"id_": "4b9b4b2f-2623-4e9c-9a37-d3635f1ed7f1", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "ac868d7b-34f4-4370-bf1d-4700af6fbb9d", "node_type": "1", "metadata": {}, "hash": "aca58b52c8cbdaa96aae50bb843c528d165fccb87447aab0a90f47567f477ba2", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "48ba59fa-ba8a-482a-83ab-d22ecc2e2f5e", "node_type": "1", "metadata": {}, "hash": "e573c3f5dd195f5ae5d7f432114d3d8cc730b95d0175b8739ff6c1f45e698242", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Table 6.6: ARV, CTX and Fluconazole Adjustments in Renal and Hepatic Impairment\u00b9\n\n| Drug | CrCl (ml/min)<br/>15 - 50 | CrCl (ml/min)<br/><15 | Haemodialysis | Liver impairment |\n| ----------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------- | --------------------- | --------------------------------------------- | ---------------------------------------------------------------------------------------------------------- |\n| ABC | No change | | | Reduce adult dose to 200 mg BD for moderate to severe liver impairment. AVOID in severe hepatic impairment |\n| AZT | No change | 300 mg/day | 300 mg/day | Reduce dose by 50% or double interval of administration in moderate to severe impairment |\n| TDF\u00b2 | AVOID unless HBV+\u00b2 | AVOID unless HBV+\u00b2 | 300 mg every 7 days | No change |\n| TAF | No change | AVOID unless HBV+\u00b2 | No dose adjustment- Administer after dialysis | No change |\n| 3TC | 150 mg OD | 150 mg OD | 75 mg OD | No change |\n| LPV | No change | | | No change, use with caution in moderate to severe impairment |\n| RTV | | | | |\n| ATV | | | | |\n| DRV | | | | |\n| RAL | No change | | | No change in mild to moderate impairment. Use with caution in severe impairment |\n| DTG | | | | |\n| EFV | No change | | | Use with caution in mild to moderate liver impairment. AVOID in severe impairment |\n| NVP | No change | | | AVOID |\n| ETV | No change | | | Use with caution in severe liver impairment |\n| CTX | If CrCl > 30 ml/min then no dose adjustment required; if 15-30 ml/min then use 50% of normal recommended dose; if CrCl < 15 ml/min then CTX should be avoided | | | Use with caution in mild to moderate liver impairment. AVOID in severe impairment |\n| Fluconazole | If CrCl \u2264 50 ml/min then use 50% of normal recommended dose (no dose adjustment required for CrCl > 50 ml/min) | | | Use with caution |\n\n\n\u00b9 Patients with evidence of renal or hepatic impairment should have access to regular monitoring of renal and liver function\n\n\u00b2 TDF and renal impairment:\n- In acute kidney injury (AKI), interrupt TDF administration until the cause of AKI is established and corrected.\n- Avoid the use of TDF in patients with CrCl < 50ml/min unless in HIV/HBV coinfection (in which case TAF or TDF should be used). For patients with HBV co-infection, the benefit of TDF or TAF for treating HBV often outweighs the risks of renal impairment, so more severe levels of renal impairment are tolerated. See Table 9.3 for TDF and TAF dose adjustments for patients with HBV/HIV co-infection. These patients should be managed in consultation with an experienced clinician\n- If HBV negative and on first line ART, substitute TDF with ABC, TAF or DTG + 3TC dual therapy, following the single drug substitution algorithm (Figure 6.4). If prior ART treatment failure or any other scenario consult the Regional or National HIV Clinical TWG (Uliza Hotline 0726 460 000; https://nhcsc.nascop.org/clinicalform)", "mimetype": "text/plain", "start_char_idx": 40196, "end_char_idx": 47784, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "48ba59fa-ba8a-482a-83ab-d22ecc2e2f5e": {"__data__": {"id_": "48ba59fa-ba8a-482a-83ab-d22ecc2e2f5e", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "4b9b4b2f-2623-4e9c-9a37-d3635f1ed7f1", "node_type": "1", "metadata": {}, "hash": "651d36d992c40f6fb40ff2827f57153094347935ffd71725963d43e2e290dc11", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "e642316e-72b6-4043-922e-540f5260fb55", "node_type": "1", "metadata": {}, "hash": "1c048cdfad9d943b6e15879a3e7d85a8102d35f9b79efd8e5aa7612e3b65b5c7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Antiretroviral Therapy in Infants, Children, Adolescents, and Adults\n\n### Table 6.7: Management of AZT-Associated Bone Marrow Suppression\n\n| Test | Result | Action |\n| --------------------- | ------------------------------------------------------------ | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |\n| Hb (g/dL) | > 8.5 (and decrease from pre-AZT baseline) | Retain AZT, repeat Hb at week 1, 2, 4 and 12 (if accessing follow-up Hb is difficult then consider substituting to an alternative ARV immediately) |\n| | \u2264 8.5 | Switch from AZT to an alternative ARV |\n| Neutrophils (x 10\u2079/L) | 1.0 \u2013 1.5 (and decrease from pre-AZT baseline, if available) | If receiving cotrimoxazole consider withholding unless essential. Retain AZT, repeat at week 1, 2, 4 and 12 (if accessing follow-up neutrophils is difficult then consider switching to an alternative ARV immediately) |\n| | \u2264 1.0 | Switch from AZT to an alternative ARV |\n\n\nNote:\n- Patients with baseline Hb of < 9.5 g/dL should not be initiated on AZT; patients who develop anaemia while on AZT should be managed as per this table\n- AZT-associated bone marrow suppression occurs early in the course of treatment, usually within 3 months of initiating ART\n- All patients with anaemia and/or neutropenia, whether on AZT or not, should be evaluated for other likely causes of anaemia/neutropenia and managed appropriately\n\n### Table 6.8: Management of Drug-Related Hepatotoxicity\n\n| ALT | <2.5 x Upper Limit of Normal (ULN) | 2.5 \u2013 5 x ULN | > 5 x ULN |\n| ------ | ---------------------------------- | -------------------------------- | ----------------------------------------------------------------------- |\n| Action | Retain regimen, repeat in 2 weeks | Retain regimen, repeat in 1 week | Discontinue offending drug/s<br/>Consult senior clinician for next step |", "mimetype": "text/plain", "start_char_idx": 47788, "end_char_idx": 50746, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e642316e-72b6-4043-922e-540f5260fb55": {"__data__": {"id_": "e642316e-72b6-4043-922e-540f5260fb55", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "48ba59fa-ba8a-482a-83ab-d22ecc2e2f5e", "node_type": "1", "metadata": {}, "hash": "e573c3f5dd195f5ae5d7f432114d3d8cc730b95d0175b8739ff6c1f45e698242", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "6314e350-d512-413c-850f-35dce0e8b5e4", "node_type": "1", "metadata": {}, "hash": "44caba82388b1d1bf85c1318bf6e76e43c2378f6574ee903471f61471e23c678", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Note: All patients with acute increase in liver enzymes should be evaluated for other likely causes of hepatitis/hepatotoxicity and managed appropriately\n\n# Table 6.9: Diagnosis and Management of Abacavir Hypersensitivity Reaction\n\n# Diagnosis\n\nWithin 3 weeks of initiating an ABC-containing regimen, patient develops any 2 of the following symptom groups concurrently:\n\n- Fever\n- Erythematous and/or pruritic rash\n- Respiratory symptoms (shortness of breath and/or sore throat and/or cough)\n- GI symptoms: nausea and/or vomiting and/or diarrhea\n- Extreme fatigue and/or body pain preventing normal activities\n\nAND: there is not a more likely alternative explanation for the symptoms\n\n# Management\n\n- Stop ABC immediately and substitute with an alternative ARV\n- Patient must NEVER be re-challenged with ABC \u2013 a single dose could result in a fatal hypersensitivity reaction\n- Clearly mark file and educate patient about avoiding ABC in future\n- Issue an Adverse Event alert card\n\n# Note:\n\n- ABC hypersensitivity reaction is rare in our population: always consider other more likely possible diagnoses\n- Symptoms generally get worse within hours after each dose of ABC\n\n# 6.5.3 Changing ARVs Due to Drug-Drug Interactions\n\nPatients must be asked about other medications (including non-prescription and herbal medicine) they are taking at every visit. Some common drugs have specific drug-drug interactions that may require dose adjustment or substitution of the ARV or the other interacting drugs.\n\nCommon medications that interact with specific ARVs include: rifampicin, rifabutin, antacids, multivitamin/mineral supplements, methadone, several anti-fungal, anti-convulsant, calcium-channel blockers, some anti-depressants, some statins, and some anti-malarial. Annex 13 provides common drug-drug interactions and management recommendations. It is recommended practice to check for interactions whenever a new medicine is started.\n\n# 6.5.4 Changing ARVs Due to Treatment Failure\n\nViral load is the test of choice for monitoring response to ART and identifying treatment failure. First VL should be performed 3 months after ART initiation for all PLHIV. Treatment failure should be suspected when a new or recurrent HIV-associated condition indicating severe immunodeficiency (WHO stage III or IV condition) develops after at least 6 months on ART. Treatment failure should always be confirmed with VL testing.\n\n# Frequency of routine VL monitoring for specific populations is:\n\n- Age 0-24 years old: at 3 months after ART initiation and then every 6 months\n- Age \u2265 25 years old: at 3 months after ART initiation, then at month 12 and then annually\n- Pregnant or breastfeeding: at confirmation of pregnancy (if already on ART) or 3 months after ART initiation (if ART initiated during pregnancy/ breastfeeding), and then every 6 months until cessation of breastfeeding\n- Before making any drug substitution (if no VL results from the prior 6 months)\n- Three months after any regimen modification (including single-drug substitutions), and then as per population group\n- For any patient with a detectable VL follow the viral load monitoring algorithm (Figure 6.6)\n\n# Interpreting Viral Load Results and Defining Treatment Failure (Figure 6.6)\n\nThe goal for ART is to achieve sustained viral suppression defined as below the Lower Detection Limit (LDL), &#x3C; 50 copies/ml is considered as suppressed. See Table 5.17\n\nPersistent low-level viremia (PLLV) is defined as having between 200-999 copies/ml on two consecutive measures. These patients are at increased risk of progression to treatment failure, development of resistance and death and therefore require a similar case management approach as patients with VL \u2265 1,000 copies/ml, and consultation with the Regional or National HIV Clinical TWG (Uliza Hotline 0726 460 000; https://nhcsc.nascop.org/clinicalform).\n\nTreatment failure is suspected when a patient has a high VL \u2265 1,000 copies/ml after at least 3 months of using ART. Treatment failure is only confirmed when VL is \u2265 1,000 copies/ml after assessing for and addressing poor adherence or other reasons for high VL, and then repeating VL after at least 3 months of enhanced adherence to allow for viral re-suppression.", "mimetype": "text/plain", "start_char_idx": 50749, "end_char_idx": 54980, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6314e350-d512-413c-850f-35dce0e8b5e4": {"__data__": {"id_": "6314e350-d512-413c-850f-35dce0e8b5e4", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "e642316e-72b6-4043-922e-540f5260fb55", "node_type": "1", "metadata": {}, "hash": "1c048cdfad9d943b6e15879a3e7d85a8102d35f9b79efd8e5aa7612e3b65b5c7", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "bf20c48d-fbb7-4586-8ff7-2504638f92b3", "node_type": "1", "metadata": {}, "hash": "74d06678ec779098307d1c0b3a4c76f54721afec621598f39f558abe9f3852b6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```mermaid\ngraph TD\n A[Schedule for routine viral load testing\u00b9] --> B[VL < 200 copies/ml]\n A --> C[VL 200 - 999 copies/ml]\n A --> D[VL \u2265 1,000 copies/ml]\n C --> E[Increased risk of progression to treatment failure]\n D --> F[Suspected treatment failure]\n E --> G[Intervention Steps]\n F --> G\n G --> H[VL 200 - 999 copies/ml]\n H --> I[Reassessment Steps]\n I --> J[VL < 200 copies/ml LDL]\n I --> K[VL 200 - 999 copies/ml]\n I --> L[VL \u2265 1,000 copies/ml]\n B --> M[Continue ART regimen]\n J --> M\n K --> N[Consult Regional or National HIV Clinical TWG or call Uliza Hotline 0726 460 000]\n L --> O[Confirms treatment failure]\n```\n\nSchedule for routine viral load testing\u00b9:\n- Age 0-24 years old: at month 3, then every 6 months\n- Age \u2265 25 years old: at month 3, then month 12 and then annually\n- Pregnant or breastfeeding: at confirmation of pregnancy (if already on ART) or 3 months after ART initiation (if ART initiated during pregnancy/breastfeeding), and then every 6 months until complete cessation of breastfeeding\n- Before any drug substitution (if no VL result available from the prior 6 months)\n- Three months after any regimen modification (including single-drug substitutions)\n\nFor VL 200 - 999 copies/ml and VL \u2265 1,000 copies/ml:\n- Discuss patient in MDT\n- Assign a case manager\n- Assess for and address likely causes of non-adherence\u00b2\n- Provide enhanced adherence support/intervention as appropriate (Section 5.4 of guidelines for enhanced adherence protocol)\n- Assess for other causes of viremia and manage as needed\u00b3\n- Support daily witnessed ingestion by treatment buddy or healthcare worker\n- After 3 months of excellent adherence, repeat VL\n\nFor VL 200 - 999 copies/ml after intervention:\n- Reassess adherence and other causes of viremia\u00b2,\u00b3\n- Repeat VL after another 3 months of excellent adherence\n\nOutcomes:\n\nVL < 200 copies/ml (LDL):\n- Continue ART regimen\n- Routine adherence counselling and monitoring\n- Routine VL monitoring\n\nVL 200 - 999 copies/ml:\nConsult Regional or National HIV Clinical TWG or call Uliza Hotline (0726 460 000)\n\nVL \u2265 1,000 copies/ml:\nConfirms treatment failure:\n- Begin treatment preparation for new regimen and continue failing regimen until adherence preparation completed\n- Continue enhanced adherence support\n- Take sample for CD4 count and assess for and manage any OIs\n- If failing a DTG or PI based regimen a DRT is recommended in consultation with the regional or National HIV Clinical TWG or call Uliza Hotline (0726 460 000)\n- Schedule clinical appointment at 2 weeks after regimen change to review adherence, side effects and any other concerns\n- Repeat VL 3 months after regimen modification\n\n1. As part of treatment preparation, patients should be informed that viral load is the recommended method of monitoring ART. VL results should always be discussed with patients, even when they are undetectable. Goals of treatment and definition of success should be discussed and adherence messaging reinforced\n2. Common causes of poor adherence include: stigma, non-disclosure, travel, toxicities, alcohol or drug use, mental health disorder, religious beliefs, inadequate treatment preparation, chaotic lifestyle, lack of support systems, and poor patient-provider relationship\n3. Other common causes of treatment failure (beyond adherence) include: inadequate dosing/dose adjustments, drug-drug interactions, drug-food interactions, impaired absorption (e.g. chronic severe diarrhoea)\n\nFigure 6.6: Viral Load Monitoring of Patients on ART (1st Line or 2nd Line)", "mimetype": "text/plain", "start_char_idx": 54984, "end_char_idx": 58541, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bf20c48d-fbb7-4586-8ff7-2504638f92b3": {"__data__": {"id_": "bf20c48d-fbb7-4586-8ff7-2504638f92b3", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "6314e350-d512-413c-850f-35dce0e8b5e4", "node_type": "1", "metadata": {}, "hash": "44caba82388b1d1bf85c1318bf6e76e43c2378f6574ee903471f61471e23c678", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "ecd89dd5-cc4b-4892-bd4a-f401da0092ec", "node_type": "1", "metadata": {}, "hash": "c2ea67f11b2a9c5c2b4448bdb47e7bfd9d4f3d3669e161d200d5bd2cb262c05e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Antiretroviral Therapy in Infants, Children, Adolescents, and Adults\n\n> Non-adherence is the most frequent cause of treatment failure. As per the viral load\nmonitoring algorithm, adherence issues must be addressed BEFORE confirming\ntreatment failure.\n\nDaily witnessed ingestion by a treatment buddy or healthcare worker is recommended to confirm\nexcellent adherence before repeating the VL. All adherence issues must be resolved before\nswitching to a new regimen otherwise the patient will quickly fail the new regimen as well, and\nsoon run out of viable ART options. An exception to this may be when the regimen itself is\nthe primary cause of poor adherence (e.g., side effects from one of the ARVs are not\nmanageable such as severe diarrhea with LPV/r that does not improve with symptom\nmanagement), in which case the regimen may need to be modified to allow for perfect adherence.\nThis should be done in consultation with the Regional or National HIV Clinical TWG.\n\nChapter 5 provides detailed guidance on adherence preparation, assessment, and support.\n\n## Table 6.10: Recommended Second-line ART Regimens in Infants, Children, Adolescents and Adults, excluding TB/HIV co-infection \u00b9\n\n| Weight/scenario | First-line ART | Second-line ART |\n| -------------------------------- | --------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------ |\n| < 30 kg | ABC (or AZT) + 3TC + DTG | DRT-based second-line\u00b2,\u00b3 |\n| | ABC + 3TC + LPV/r | Take sample for DRT and change to AZT + 3TC + DTG while awaiting DRT results; modify based on DRT results if indicated |\n| | AZT + 3TC + LPV/r | Take sample for DRT and change to ABC + 3TC + DTG while awaiting DRT results; modify based on DRT results if indicated |\n| | ABC + 3TC + EFV | AZT + 3TC + DTG |\n| | AZT + 3TC + EFV | ABC + 3TC + DTG |\n| \u2265 30 kg or \u2265 15 years old | TDF (or ABC) + 3TC + DTG (or PI/r) | DRT-based second-line\u00b2 |\n| | TDF (or ABC) + 3TC + EFV | TDF + 3TC + DTG |\n| | AZT + 3TC + EFV | TDF + 3TC + DTG |\n| Pregnant and Breastfeeding women | TDF (or ABC) + 3TC + DTG | Take sample for DRT and change to TDF + 3TC + ATV/r while awaiting DRT results; modify based on DRT results if indicated |\n| | TDF (or ABC) + 3TC + PI/r | Take sample for DRT and change to TDF + 3TC + DTG while awaiting DRT results; modify based on DRT results if indicated |\n| | TDF (or ABC) + 3TC + EFV | TDF + 3TC + DTG |\n| | AZT + 3TC + EFV | TDF + 3TC + DTG |\n| HIV/HBV Co-infection | Always maintain TDF in order to treat the HBV as well as HIV | |\n| TB/HIV Co-infection | Refer to Table 8.8: Recommended ART Regimens for Patients who Develop TB while Failing 1\u02e2\u1d57 Line ART | |", "mimetype": "text/plain", "start_char_idx": 58545, "end_char_idx": 63927, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ecd89dd5-cc4b-4892-bd4a-f401da0092ec": {"__data__": {"id_": "ecd89dd5-cc4b-4892-bd4a-f401da0092ec", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "bf20c48d-fbb7-4586-8ff7-2504638f92b3", "node_type": "1", "metadata": {}, "hash": "74d06678ec779098307d1c0b3a4c76f54721afec621598f39f558abe9f3852b6", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "a4d5323d-c2f4-44df-b88d-33a79585f6cc", "node_type": "1", "metadata": {}, "hash": "806fa6835df9127b05115db5532f36f13d5ed2be79e3fd5385f2a7daf756d094", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Table 6.10 Cont.\n\n1. If any drug in the recommended 2nd line regimen is contraindicated or previously not tolerated, consult the Regional or National HIV Clinical TWG (Uliza Hotline 0726 460 000; https://nhcsc.nascop.org/clinicalform). Such patients may require DRT to select agents for the second-line ART. Additional drugs may be recommended on a case-by-case basis, including DRV/r, ATV/r, RAL, or ETR.\n2. Patients failing DTG-based or PI-based first-line regimens should have a Drug Resistance Test (DRT) ordered as soon as treatment failure is confirmed. The patient summary and DRT results should be sent to the Regional or National HIV Clinical TWG (https://nhcsc.nascop.org/clinicalform) or call Uliza Hotline (0726 460 000) to determine the most suitable second-line regimen for the patient. The DRT results will be used to determine if there is true DTG or PI failure or if there is an underlying problem with non-adherence. Daily witnessed ingestion is recommended prior to performing DRT.\n\n# Important Considerations for First-line Treatment Failure in Children\n\n- Second-line ART in infants and children is more complex to manage. These children and their caregivers should undergo thorough clinical and psychosocial assessment to rule out inter-current illness or non-adherence as the reason for a high viral load.\n- All children failing first-line should be discussed in the MDT and preferably with an experienced ART provider prior to change of ART to second-line. However, this should not cause undue delay in switching a failing regimen.\n- The choices for infants and children failing an alternative first-line regimen are limited and may need to be discussed with the Regional or National HIV Clinical TWG. Some of these children will require HIV DRT to determine the most suitable second-line regimen.\n\n# Important considerations for second-line ART Treatment Failure\n\n- Patients failing second-line ART have limited options. ARVs used to construct a third-line regimen are often more expensive, will have increased pill burden and more side effects. These factors will exacerbate pre-existing poor adherence.\n- Second-line treatment failure should be confirmed by viral load testing following the viral load monitoring algorithm (Figure 6.6).\n1. After the first detectable VL (\u2265 50 copies/ml), assess for and address all causes of poor adherence, and assess for all other possible causes of viremia.\n2. These patients should be discussed at an MDT session. Repeat the VL after 3 months of excellent adherence (preferably with daily witnessed ingestion of the ARVs by a treatment buddy, relative, CHV, etc.).\n3. If the second VL is still \u2265 50 copies/ml then continue the failing second-line regimen while reassessing adherence and other causes of viremia, implementing adherence support systems as needed, and then repeat the VL after another 3 months.\n4. If viremia continues then consult the Regional or National HIV Clinical TWG (Uliza Hotline 0726 460 000; https://nhcsc.nascop.org/clinicalform) using the national case summary form (Annex 9B). These patients will likely require DRT in order for the TWG to design the most suitable third-line regimen.\n- Patients failing second-line ART require thorough assessment for barriers to adherence and ongoing enhanced adherence support including:\n- Assigning a case manager\n- More frequent adherence counselling by a trained counsellor\n- Assessment and treatment of mental health and substance use disorders", "mimetype": "text/plain", "start_char_idx": 63933, "end_char_idx": 67411, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a4d5323d-c2f4-44df-b88d-33a79585f6cc": {"__data__": {"id_": "a4d5323d-c2f4-44df-b88d-33a79585f6cc", "embedding": null, "metadata": {}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119", "node_type": "4", "metadata": {}, "hash": "bf98618b57dc152a78134cbf1eacd6a5ed074949846ad0ad4eaaaea3882e2b27", "class_name": "RelatedNodeInfo"}, "2": {"node_id": "ecd89dd5-cc4b-4892-bd4a-f401da0092ec", "node_type": "1", "metadata": {}, "hash": "c2ea67f11b2a9c5c2b4448bdb47e7bfd9d4f3d3669e161d200d5bd2cb262c05e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Antiretroviral Therapy in Infants, Children, Adolescents, and Adults\n\n## Table 6.11: Possible Third-line ART in Children, Adolescents and Adults\n\n| | Possible 3\u02b3\u1d48 Line Regimen | Comment |\n| -------- | -------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |\n| Children | DTG + 3TC + DRV/r | Third line ART selection is based on DRT results<br/><br/>Note that the Regional or National HIV Clinical TWG may recommend reusing some of the ARVs the patient has already failed, even when resistance is present |\n| | DTG + AZT + 3TC + DRV/r | |\n| | DTG + ABC (or TDF) + 3TC + DRV/r | |\n| | ETV + 3TC + DRV/r | |\n| Adults | DTG + 3TC + DRV/r | |\n| | DTG + AZT + 3TC + DRV/r | |\n| | DTG + TDF + 3TC + DRV/r | |\n| | DTG + TDF (or AZT) + 3TC | |\n| | ETV + 3TC + DRV/r | |\n\n\n\n\nNO_CONTENT_HERE", "mimetype": "text/plain", "start_char_idx": 67417, "end_char_idx": 70477, "metadata_seperator": "\n", "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}}, "docstore/metadata": {"578d2aee-7c6e-4369-ae78-9276a7a6e9a6": {"doc_hash": "909fe5c6ecb57ef45ea9db56e1b5328c905525ab2418dcc77d625132b2f49803", "ref_doc_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119"}, "c73b2029-bbda-4c95-aad2-520b71807f4c": {"doc_hash": "7d0b3340dcf97448ea73fa055738400c6a59960a36870f9bfdd7ecb154cdbf3b", "ref_doc_id": "c54f6a50-4346-4cb1-8e6a-e32dd10e2119"}, "c4686376-337b-450c-bf0c-dac37456fed8": {"doc_hash": 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