ART Guidelines

ART Guidelines


Please review the disclaimer before proceeding with these guidelines

×

×





  • ×
  • ABBREVIATIONS
    /r ritonavir-boosted
    3TC lamivudine
    ABC abacavir
    ADR adverse drug reaction
    AKI acute kidney injury
    ALT alanine transaminase
    ART antiretroviral therapy
    ARV antiretroviral
    AST aspartate transaminase
    ATV atazanavir
    ATV/r ritonavir-boosted atazanavir
    AZT zidovudine
    bd twice daily
    CD4+ cluster of differentiation 4
    CM cryptococcal meningitis
    CrAg cryptococcal antigen
    CrCl creatinine clearance rate
    CSF cerebrospinal fluid
    CTX cotrimoxazole
    CVS cardiovascular
    d4T stavudine
    DILI drug-induced liver injury
    DNA deoxyribonucleic acid
    DOR doravirine
    DRV darunavir
    DRV/r ritonavir-boosted darunavir
    DTG dolutegravir
    eGFR estimated glomerular filtration rate
    ELISA enzyme-linked immunosorbent assay
    ETR etravirine
    FBC full blood count
    FDC fixed dose combination
    FTC emtricitabine
    GI gastrointestinal
    Hb haemoglobin
    HBsAg hepatitis B surface antigen
    HBV hepatitis B virus
    HIV human immunodeficiency virus
    ICU intensive care unit
    InSTI integrase strand transfer inhibitor
    IPT isoniazid preventive therapy
    LAM lipoarabinomannan
    LDL-C low-density lipoprotein cholesterol
    LP lumbar puncture
    LPV lopinavir
    LPV/r ritonavir-boosted lopinavir
    MDRD modification of diet in renal disease
    MTCT mother-to-child transmission of HIV
    MVC maraviroc
    NGT nasogastric tube
    NNRTI non-nucleoside reverse transcriptase inhibitor
    NRTI nucleoside reverse transcriptase inhibitor
    NTDs neural-tube defects
    NtRTI nucleotide reverse transcriptase inhibitor
    NVP nevirapine
    OI opportunistic infection
    PCR polymerase chain reaction
    PI protease inhibitor
    PI/r ritonavir-boosted protease inhibitor
    PMTCT prevention of mother-to-child transmission of HIV
    PPIs proton pump inhibitors
    PrEP pre-exposure prophylaxis
    PWH people with HIV
    RAL raltegravir
    RCTs randomised controlled trials
    RIF rifampicin
    RFB rifabutin
    RNA ribonucleic acid
    RPV rilpivirine
    RTV or /r ritonavir
    sCr serum creatinine
    sCrAg serum cryptococcal antigen
    TAF tenofovir alafenamide
    TAM thymidine analogue mutation
    TB tuberculosis
    TB-IRIS tuberculosis immune reconstitution inflammatory syndrome
    TBM tuberculosis meningitis
    TC total cholesterol
    TDF tenofovir disoproxil fumarate
    TG triglycerides
    TST tuberculin skin test
    ULN upper limit of normal
    VL viral load
    VTP vertical transmission prevention of HIV
    WHO World Health Organization










    References:

    1. Maartens G. ‘Covering the tail’after stopping efavirenz-based antiretroviral therapy. Southern African Journal of HIV Medicine. 2020;21(1):1-2.

    2. Majluf‐Cruz A, Luna‐Castaños G, Treviño‐Pérez S, Santoscoy M, Nieto‐Cisneros L. Lamivudine‐induced pure red cell aplasia. American journal of hematology. 2000;65(3):189-191.

    3. Cohen K, Viljoen C, Njuguna C, Maartens G. Emtricitabine-associated red cell aplasia. AIDS. 2019;33(6):1095-1096

    4. Paton NI, Musaazi J, Kityo C, et al. Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial. Lancet HIV. Apr 20 2022.

    5. Fernandez-Fernandez B, Montoya-Ferrer A, Sanz AB, et al. Tenofovir nephrotoxicity: 2011 update. AIDS Res Treat. 2011;2011:354908.

    6. Venter WDF, Fabian J, Feldman C. An overview of tenofovir and renal disease for the HIV-treating clinician. South Afr J HIV Med. 2018;19(1):817.

    7. Pilkington V, Hughes SL, Pepperrell T, et al. Tenofovir alafenamide vs. tenofovir disoproxil fumarate: an updated metaanalysis of 14 894 patients across 14 trials. Aids. Dec 1 2020;34(15):2259-2268.

    8. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. Jun 27 2015;385(9987):2606-2615.

    9. Mallon PW, Brunet L, Hsu RK, et al. Weight gain before and after switch from TDF to TAF in a U.S. cohort study. J Int AIDS Soc. Apr 2021;24(4):e25702.

    10. Venter WDF, Sokhela S, Simmons B, et al. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, non-inferiority trial. Lancet HIV. Oct 2020;7(10):e666-e676.

    11. Schafer JJ, Sassa KN, O’Connor JR, Shimada A, Keith SW, DeSimone JA. Changes in Body Mass Index and Atherosclerotic Disease Risk Score After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide. Open Forum Infect Dis. Oct 2019;6(10):ofz414.

    12. Cerrone M, Alfarisi O, Neary M, et al. Rifampicin effect on intracellular and plasma pharmacokinetics of tenofovir alafenamide. Journal of Antimicrobial Chemotherapy. 2019;74(6):1670-1678.

    13. Cruciani M, Mengoli C, Malena M, et al. Virological efficacy of abacavir: systematic review and meta-analysis. J Antimicrob Chemother. Dec 2014;69(12):3169-3180.

    14. D. A. D. Study Group, Sabin CA, Worm SW, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. Apr 26 2008;371(9622):1417-1426.

    15. Ribaudo HJ, Benson CA, Zheng Y, et al. No risk of myocardial infarction associated with initial antiretroviral treatment containing abacavir: short and long-term results from ACTG A5001/ALLRT. Clin Infect Dis. Apr 1 2011;52(7):929-940.

    16. Dean L. Abacavir therapy and HLA-B* 57: 01 genotype. 2018.

    17. Raffi F, Jaeger H, Quiros-Roldan E, et al. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. Nov 2013;13(11):927-935.

    18. You J, Wang H, Huang X, et al. Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials. PLoS One. 2016;11(8):e0160087.

    19. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. Nov 7 2013;369(19):1807-1818.

    20. Molina JM, Clotet B, van Lunzen J, et al. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study. Lancet HIV. Apr 2015;2(4):e127-136.

    21. Orrell C, Hagins DP, Belonosova E, et al. Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavirboosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study. Lancet HIV. Dec 2017;4(12):e536-e546.

    22. Aboud M, Kaplan R, Lombaard J, et al. Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial. Lancet Infect Dis. Mar 2019;19(3):253-264

    23. Cevik M, Orkin C, Sax PE. Emergent Resistance to Dolutegravir Among INSTI-Naïve Patients on First-line or Second-line Antiretroviral Therapy: A Review of Published Cases. Open Forum Infect Dis. Jun 2020;7(6):ofaa202.

    24. Schramm B, Temfack E, Descamps D, et al. Viral suppression and HIV-1 drug resistance 1 year after pragmatic transitioning to dolutegravir first-line therapy in Malawi: a prospective cohort study. Lancet HIV. Aug 2022;9(8):e544-e553.

    25. Turkova A, White E, Mujuru HA, et al. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. N Engl J Med. Dec 30 2021;385(27):2531-2543.

    26. Zash R, Holmes L, Diseko M, et al. Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana. N Engl J Med. Aug 29 2019;381(9):827-840.

    27. Zash RH, LB; Diseko, M; Jacobson, D; Mayondi, G; Mabuta, J; Mmalane, M; Gaolathe, T; Lockman, S; Makhema, J; Shapiro, R. Update on neural tube defects with antiretroviral exposure in the Tsepamo Study, Botswana. AIDS 2022. Montréal, Canada2022.

    28. Chouchana L, Beeker N, Treluyer JM. Is There a Safety Signal for Dolutegravir and Integrase Inhibitors During Pregnancy? J Acquir Immune Defic Syndr. Aug 1 2019;81(4):481-486.

    29. Pereira GFM, Kim A, Jalil EM, et al. Dolutegravir and pregnancy outcomes in women on antiretroviral therapy in Brazil: a retrospective national cohort study. Lancet HIV. Jan 2021;8(1):e33-e41.

    30. Kintu K, Malaba TR, Nakibuka J, et al. Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial. Lancet HIV. May 2020;7(5):e332-e339.

    31. Lockman S, Brummel SS, Ziemba L, et al. Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. Apr 3 2021;397(10281):1276-1292.

    32. Patel K, Huo Y, Jao J, et al. Dolutegravir in Pregnancy as Compared with Current HIV Regimens in the United States. New England Journal of Medicine. 2022;387(9):799-809.

    33. Malaba TR, Nakatudde I, Kintu K, et al. 72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study. The Lancet HIV. 2022;9(8):e534-e543.

    34. Griesel R, Maartens G, Chirehwa M, et al. CYP2B6 Genotype and Weight Gain Differences Between Dolutegravir and Efavirenz. Clin Infect Dis. Dec 6 2021;73(11):e3902-e3909.

    35. Griesel R, Kawuma AN, Wasmann R, et al. Concentration-response relationships of dolutegravir and efavirenz with weight change after starting antiretroviral therapy. Br J Clin Pharmacol. Mar 2022;88(3):883-893.

    36. Griesel R, Maartens G, Chirehwa M, et al. CYP2B6 genotype and weight gain differences between dolutegravir and efavirenz. Clinical Infectious Diseases. 2021;73(11):e3902-e3909.

    37. Modongo C, Wang Q, Dima M, et al. Clinical and Virological Outcomes of TB/HIV Coinfected Patients Treated With Dolutegravir-Based HIV Antiretroviral Regimens: Programmatic Experience From Botswana. J Acquir Immune Defic Syndr. Oct 1 2019;82(2):111-115.

    38. Griesel R, Hill A, Meintjes G, Maartens G. Standard versus double dose dolutegravir in patients with HIV-associated tuberculosis: a phase 2 non-comparative randomised controlled (RADIANT-TB) trial. Wellcome Open Research. 2021;6

    39. Encore Study Group, Carey D, Puls R, et al. Efficacy and safety of efavirenz 400 mg daily versus 600 mg daily: 96-week data from the randomised, double-blind, placebo-controlled, non-inferiority ENCORE1 study. Lancet Infect Dis. Jul 2015;15(7):793-802.

    40. Variava E, Sigauke FR, Norman J, et al. Brief Report: Late Efavirenz-Induced Ataxia and Encephalopathy: A Case Series. J Acquir Immune Defic Syndr. Aug 15 2017;75(5):577-579.

    41. Sinxadi PZ, Leger PD, McIlleron HM, et al. Pharmacogenetics of plasma efavirenz exposure in HIV-infected adults and children in South Africa. Br J Clin Pharmacol. Jul 2015;80(1):146-156.

    42. Sonderup MW, Maughan D, Gogela N, et al. Identification of a novel and severe pattern of efavirenz drug-induced liver injury in South Africa. AIDS. Jun 1 2016;30(9):1483-1485.

    43. Jover F, Cuadrado JM, Roig P, Rodriguez M, Andreu L, Merino J. Efavirenz-associated gynecomastia: report of five cases and review of the literature. Breast J. May-Jun 2004;10(3):244-246.

    44. Sikora MJ, Rae JM, Johnson MD, Desta Z. Efavirenz directly modulates the oestrogen receptor and induces breast cancer cell growth. HIV Med. Oct 1 2010;11(9):603-607.

    45. Njuguna C, Swart A, Blockman M, et al. Cases of antiretroviral-associated gynaecomastia reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa. AIDS Res Ther. 2016;13:40.

    46. Cohen CJ, Molina JM, Cassetti I, et al. Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials. AIDS. Mar 27 2013;27(6):939-950.

    47. Behrens G, Rijnders B, Nelson M, et al. Rilpivirine versus efavirenz with emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV-1-infected patients with HIV-1 RNA
    48. Katlama C, Clotet B, Mills A, et al. Efficacy and safety of etravirine at week 96 in treatment-experienced HIV type-1-infected patients in the DUET-1 and DUET-2 trials: SAGE Publications Sage UK: London, England; 2010.

    49. Cohen C, Nieto-Cisneros L, Zala C, et al. Comparison of atazanavir with lopinavir/ritonavir in patients with prior protease inhibitor failure: a randomized multinational trial. Curr Med Res Opin. Oct 2005;21(10):1683-1692.

    50. Mills AM, Nelson M, Jayaweera D, et al. Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS. Aug 24 2009;23(13):1679-1688.

    51. Venter WDF, Moorhouse M, Sokhela S, et al. Low-dose ritonavir-boosted darunavir once daily versus ritonavir-boosted lopinavir for participants with less than 50 HIV RNA copies per mL (WRHI 052): a randomised, open-label, phase 3, noninferiority trial. Lancet HIV. Jul 2019;6(7):e428-e437.

    52. Molina JM, Gallien S, Chaix ML, et al. Low-dose ritonavir-boosted darunavir in virologically suppressed HIV-1-infected adults: an open-label trial (ANRS 165 Darulight). J Antimicrob Chemother. Aug 1 2018;73(8):2129-2136.

    53. Insight Start Study Group, Lundgren JD, Babiker AG, et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. Aug 27 2015;373(9):795-807.

    54. Temprano Anrs Study Group, Danel C, Moh R, et al. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. Aug 27 2015;373(9):808-822.

    55. Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. N Engl J Med. Sep 1 2016;375(9):830-839.

    56. Rodger AJ, Cambiano V, Bruun T, et al. Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy. JAMA. Jul 12 2016;316(2):171-181.

    57. Rodger AJ, Cambiano V, Bruun T, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet. Jun 15 2019;393(10189):2428-2438.

    58. Bavinton BR, Pinto AN, Phanuphak N, et al. Viral suppression and HIV transmission in serodiscordant male couples: an international, prospective, observational, cohort study. Lancet HIV. Aug 2018;5(8):e438-e447.

    59. Johnson LF, Meyer-Rath G, Dorrington RE, et al. The effect of HIV programs in South Africa on national HIV incidence trends, 2000–2019. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2022;90(2):115-123.

    60. Vandormael A, Akullian A, Siedner M, de Oliveira T, Bärnighausen T, Tanser F. Declines in HIV incidence among men and women in a South African population-based cohort. Nature communications. 2019;10(1):5482.

    61. O’Brien M, Markowitz M. Should we treat acute HIV infection? Curr HIV/AIDS Rep. Jun 2012;9(2):101-110.

    62. Okulicz JF, Lambotte O. Epidemiology and clinical characteristics of elite controllers. Current Opinion in HIV and AIDS. 2011;6(3):163-168.

    63. Krishnan S, Wilson EM, Sheikh V, et al. Evidence for innate immune system activation in HIV type 1-infected elite controllers. J Infect Dis. Mar 2014;209(6):931-939.

    64. Crowell TA, Gebo KA, Blankson JN, et al. Hospitalization Rates and Reasons Among HIV Elite Controllers and Persons With Medically Controlled HIV Infection. J Infect Dis. Jun 1 2015;211(11):1692-1702.

    65. Li JZ, Segal FP, Bosch RJ, et al. ART reduces T cell activation and immune exhaustion markers in HIV controllers. Clin Infect Dis. May 25 2019.

    66. Amanyire G, Semitala FC, Namusobya J, et al. Effects of a multicomponent intervention to streamline initiation of antiretroviral therapy in Africa: a stepped-wedge cluster-randomised trial. Lancet HIV. Nov 2016;3(11):e539-e548.

    67. Pilcher CD, Ospina-Norvell C, Dasgupta A, et al. The Effect of Same-Day Observed Initiation of Antiretroviral Therapy on HIV Viral Load and Treatment Outcomes in a US Public Health Setting. J Acquir Immune Defic Syndr. Jan 1 2017;74(1):44-51.

    68. Rosen S, Maskew M, Fox MP, et al. Initiating Antiretroviral Therapy for HIV at a Patient’s First Clinic Visit: The RapIT Randomized Controlled Trial. PLoS Med. May 2016;13(5):e1002015.

    69. Uthman OA, Okwundu C, Gbenga K, et al. Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis: A Systematic Review and Meta-analysis. Ann Intern Med. Jul 7 2015;163(1):32-39

    70. Torok ME, Yen NT, Chau TT, et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)-- associated tuberculous meningitis. Clin Infect Dis. Jun 2011;52(11):1374-1383.

    71. Boulware DR, Meya DB, Muzoora C, et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med. Jun 26 2014;370(26):2487-2498.

    72. Zolopa A, Andersen J, Powderly W, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS One. 2009;4(5):e5575.

    73. Ford N, Patten G, Rangaraj A, Davies M-A, Meintjes G, Ellman T. Outcomes of people living with HIV after hospital discharge: a systematic review and meta-analysis. The Lancet HIV. 2022;9(3):e150-e159.

    74. Tucker JD, Bien CH, Easterbrook PJ, et al. Optimal strategies for monitoring response to antiretroviral therapy in HIV-infected adults, adolescents, children and pregnant women: a systematic review. AIDS. Mar 2014;28 Suppl 2:S151-160.

    75. Hermans LE, Moorhouse M, Carmona S, et al. Effect of HIV-1 low-level viraemia during antiretroviral therapy on treatment outcomes in WHO-guided South African treatment programmes: a multicentre cohort study. Lancet Infect Dis. Feb 2018;18(2):188-197.

    76. Laprise C, de Pokomandy A, Baril JG, Dufresne S, Trottier H. Virologic failure following persistent low-level viremia in a cohort of HIV-positive patients: results from 12 years of observation. Clin Infect Dis. Nov 2013;57(10):1489-1496.

    77. Chimukangara B, Lessells RJ, Rhee SY, et al. Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis. EClinicalMedicine. Mar 2019;9:26-34.

    78. Lilian RR, Rees K, Mabitsi M, McIntyre JA, Struthers HE, Peters RP. Baseline CD4 and mortality trends in the South African human immunodeficiency virus programme: Analysis of routine data. Southern African journal of HIV medicine. 2019;20(1):1-10.

    79. Smith CJ, Sabin CA, Lampe FC, et al. The potential for CD4 cell increases in HIV-positive individuals who control viraemia with highly active antiretroviral therapy. AIDS. May 2 2003;17(7):963-969.

    80. Loutfy MR, Genebat M, Moore D, et al. A CD4+ cell count < 200 cells per cubic millimeter at 2 years after initiation of combination antiretroviral therapy is associated with increased mortality in HIV-infected individuals with viral suppression. J Acquir Immune Defic Syndr. Dec 2010;55(4):451-459.

    81. Tuboi SH, Pacheco AG, Harrison LH, et al. Mortality associated with discordant responses to antiretroviral therapy in resource-constrained settings. J Acquir Immune Defic Syndr. Jan 2010;53(1):70-77.

    82. Ledergerber B, Lundgren JD, Walker AS, et al. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1- infected individuals with virological failure to all three antiretroviral-drug classes. Lancet. Jul 3-9 2004;364(9428):51-62.

    83. Paton NI, Musaazi J, Kityo C, et al. Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial. The Lancet HIV. 2022.

    84. Moore CL, Turkova A, Mujuru H, et al. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing. BMC infectious diseases. 2021;21(1):1-14.

    85. Paton NI, Kityo C, Hoppe A, et al. Assessment of second-line antiretroviral regimens for HIV therapy in Africa. N Engl J Med. Jul 17 2014;371(3):234-247.

    86. La Rosa AM, Harrison LJ, Taiwo B, et al. Raltegravir in second-line antiretroviral therapy in resource-limited settings (SELECT): a randomised, phase 3, non-inferiority study. Lancet HIV. Jun 2016;3(6):e247-258.

    87. WHO HIV drug resistance report 2012. Available here: https://www.hst.org.za/publications/NonHST%20Publications/9789241503938_eng.pdf

    88. Dooley KE, Kaplan R, Mwelase N, et al. Dolutegravir-Based Antiretroviral Therapy for Patients Co-Infected with Tuberculosis and Hiv: A Multicenter, Noncomparative, Open-Label, Randomized Trial. Clin Infect Dis. Mar 28 2019.

    89. Rhee SY, Grant PM, Tzou PL, et al. A systematic review of the genetic mechanisms of dolutegravir resistance. J Antimicrob Chemother. Nov 1 2019;74(11):3135-3149.

    90. Gupta RK, Gregson J, Parkin N, et al. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis. Lancet Infect Dis. Mar 2018;18(3):346-355.

    91. Lamorde M, Wang X, Neary M, et al. Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics of Efavirenz 400 mg Once Daily During Pregnancy and Post-Partum. Clin Infect Dis. Aug 16 2018;67(5):785-790.

    92. Kaboggoza JP, Wang X, Neary M, et al. A Lower Dose of Efavirenz Can Be Coadministered With Rifampicin and Isoniazid in Tuberculosis Patients. Open Forum Infect Dis. Feb 2019;6(2):ofz035.

    93. Cahn P, Madero JS, Arribas JR, et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. Jan 12 2019;393(10167):143-155.

    94. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir–lamivudine for the treatment of HIV-1 infection. New England Journal of Medicine. 2013;369(19):1807-1818.

    95. Esber A, Dear N, Shah N, et al. Brief Report: Virologic Impact of the Dolutegravir Transition: Prospective Results From the Multinational African Cohort Study. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2022;91(3):285-289.

    96. Aboud M, Kaplan R, Lombaard J, et al. Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial. The Lancet Infectious Diseases. 2019;19(3):253-264.

    97. Paton NI, Musaazi J, Kityo C, et al. Dolutegravir or darunavir in combination with zidovudine or tenofovir to treat HIV. New England Journal of Medicine. 2021;385(4):330-341.

    98. Mulenga L, Fwoloshi S, Mweemba A. Dolutegravir with recycled nRTIs is noninferior to PI-based ART: VISEND trial. Paper presented at: The 29th Conference on Retroviruses and Opportunistic Infections2022.

    99. Llibre JM, Hung CC, Brinson C, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. Mar 3 2018;391(10123):839-849.

    100. Meintjes G. Antiretroviral therapy in second-line: investigating tenofovir-lamivudine-dolutegravir (ARTIST): a randomised controlled trial. 2022.

    101. Zhao Y, Griesel R, Omar Z, et al. Initial supplementary dose of dolutegravir in second-line antiretroviral therapy: a noncomparative, double-blind, randomised placebo-controlled trial. Clinical Infectious Diseases. 2023.

    102. Penner J, Ombajo L, Nkuranga J, et al. Switching treatment-experienced, integrase inhibitor-naïve, virally suppressed HIV1 infected adults from ritonavir-boosted protease inhibitors to dolutegravir: design, methods, and baseline results of a randomized, open-label, non-inferiority trial. F1000Research. 2022;11(881):881.

    103. Stevens WS, Wallis CL, Sanne I, Venter F. Will etravirine work in patients failing nonnucleoside reverse transcriptase inhibitorbased treatment in southern Africa? J Acquir Immune Defic Syndr. Dec 2009;52(5):655-656.

    104. Cahn P, Pozniak AL, Mingrone H, et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitornaive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. Aug 24 2013;382(9893):700-708.

    105. Meintjes G, Brust JCM, Nuttall J, Maartens G. Management of active tuberculosis in adults with HIV. Lancet HIV. Jul 2019;6(7):e463-e474.

    106. Modongo C, Wang Q, Dima M, et al. Clinical and virological outcomes of TB/HIV co-infected patients treated with dolutegravirbased HIV antiretroviral regimens: Programmatic experience from Botswana. Journal of acquired immune deficiency syndromes (1999). 2019;82(2):111.

    107. la Porte CJ, Colbers EP, Bertz R, et al. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. May 2004;48(5):1553-1560

    108. Decloedt EH, Maartens G, Smith P, Merry C, Bango F, McIlleron H. The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy. PLoS One. 2012;7(3):e32173.

    109. Davies G, Cerri S, Richeldi L. Rifabutin for treating pulmonary tuberculosis. Cochrane Database Syst Rev. Oct 17 2007(4):CD005159.

    110. Hennig S, Svensson EM, Niebecker R, et al. Population pharmacokinetic drug-drug interaction pooled analysis of existing data for rifabutin and HIV PIs. J Antimicrob Chemother. May 2016;71(5):1330-1340.

    111. National Committee on the Confidential Enquiries into Maternal Deaths. Saving Mothers 2017-2019: Seventh triennial report on confidential enquiries into maternal deaths in South Africa. 2020.

    112. Updated South African ART guidelines for use of dolutegravir (DTG) in pregnant women and women of childbearing potential (WOCP) Southern African HIV Clinicians Society (SAHCS); 2021.

    113. Lockman S, Brummel SS, Ziemba L, et al. Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial. The Lancet. 2021;397(10281):1276-1292.

    114. Benhamou Y, Bochet M, Thibault V, et al. Long‐term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus–infected patients. Hepatology. 1999;30(5):1302-1306.

    115. Chang M-L, Liaw Y-F. Hepatitis B flares in chronic hepatitis B: pathogenesis, natural course, and management. Journal of hepatology. 2014;61(6):1407-1417.

    116. Fischetti B, Shah K, Taft DR, Berkowitz L, Bakshi A, Cha A. Real-world experience with higher-than-recommended doses of lamivudine in patients with varying degrees of renal impairment. Paper presented at: Open Forum Infectious Diseases2018.

    117. van Coppenhagen B, Duvenage HS. Prevalence of depression in people living with HIV and AIDS at the Kalafong Provincial Tertiary Hospital Antiretroviral Clinic. S Afr J Psychiatr. 2019;25:1175.

    118. Bhana A, Rathod SD, Selohilwe O, Kathree T, Petersen I. The validity of the Patient Health Questionnaire for screening depression in chronic care patients in primary health care in South Africa. BMC psychiatry. 2015;15:1-9.

    119. Petersen I, Bhana A, Fairall LR, et al. Evaluation of a collaborative care model for integrated primary care of common mental disorders comorbid with chronic conditions in South Africa. BMC psychiatry. 2019;19:1-11.

    120. Bhana A, Mntambo N, Gigaba S, et al. Validation of a brief mental health screening tool for common mental disorders in primary healthcare. South African Medical Journal. 2019;109(4):278-283.

    121. Grant M, Petersen I, Mthethwa L, Luvuno Z, Bhana A. Accuracy of a community mental health education and detection (CMED) tool for common mental disorders in KwaZulu-Natal, South Africa. International Journal of Mental Health Systems. 2022;16(1):44

    122. Chan P, Yoon B, Colby D, et al. Immunological, cognitive and psychiatric outcomes after initiating EFV-and DTG-based antiretroviral therapy during acute HIV infection. Clin Infect Dis. 2022:ciac466.

    123. Chan P, Yoon B, Colby D, et al. Immunological, Cognitive, and Psychiatric Outcomes After Initiating Efavirenz-and Dolutegravir-based Antiretroviral Therapy During Acute Human Immunodeficiency Virus Infection. Clinical Infectious Diseases. 2023;76(3):e718-e726.

    124. Jong E, Conradie F, Berhanu R, et al. Consensus statement: Management of drug-induced liver injury in HIV-positive patients treated for TB. 2013. 2013-09-17 2013;14(3):7.

    125. SEMDSA Type 2 Diabetes Guidelines Expert Committee. SEMDSA 2017 Guidelines for the Management of Type 2 diabetes mellitus. 2017. https://www.semdsa.org.za/images/647-4385-1-PB.pdf.

    126. Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS research and therapy. 2007;4:1-10.

    127. Haddow LJ, Colebunders R, Meintjes G, et al. Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: proposed clinical case definitions. The Lancet infectious diseases. Nov 2010;10(11):791-802.

    128. Meintjes G, Lawn SD, Scano F, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. The Lancet infectious diseases. Aug 2008;8(8):516-523.

    129. Meintjes G, Wilkinson RJ, Morroni C, et al. Randomized placebo-controlled trial of prednisone for paradoxical tuberculosisassociated immune reconstitution inflammatory syndrome. AIDS. Sep 24 2010;24(15):2381-2390.

    130. Meintjes G, Sonderup MW. A practical approach to the diagnosis and management of paradoxical tuberculosis immune reconstitution inflammatory syndrome. Continuing Medical Education. 2011;29(10):410-417.

    131. Meintjes G, Stek C, Blumenthal L, et al. Prednisone for the Prevention of Paradoxical Tuberculosis-Associated IRIS. N Engl J Med. Nov 15 2018;379(20):1915-1925.

    132. Rangaka MX, Wilkinson RJ, Boulle A, et al. Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised doubleblind, placebo-controlled trial. Lancet. Aug 23 2014;384(9944):682-690.

    133. Group TAS, Danel C, Moh R, et al. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. Aug 27 2015;373(9):808-822.

    134. Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. New England Journal of Medicine. 2011;365(23):2155-2166.

    135. Swindells S, Ramchandani R, Gupta A, et al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. New England Journal of Medicine. 2019;380(11):1001-1011.

    136. Dooley KE, Savic R, Gupte A, et al. Once-weekly rifapentine and isoniazid for tuberculosis prevention in patients with HIV taking dolutegravir-based antiretroviral therapy: a phase 1/2 trial. The Lancet HIV. 2020;7(6):e401-e409.

    137. Marjorie Z. Imperial AL, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C. Arduino, Wadzanai Samaneka, Kelly Dooley, Rada Savic, Anthony T. Podany. DTG PK in people with HIV receiving daily 1HP for Latent TB treatment Conference on Retroviruses and Opportunistic Infections (CROI)2022.

    138. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. : U.S. Department of Health and Human Services, Panel on Antiretroviral Guidelines for Adults and Adolescents.; 2021.

    139. Getahun H, Kittikraisak W, Heilig CM, et al. Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS Med. Jan 18 2011;8(1):e1000391.

    140. Gupta A, Montepiedra G, Aaron L, et al. Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women. N Engl J Med. Oct 3 2019;381(14):1333-1346.

    141. Kalk E, Heekes A, Mehta U, et al. Safety and Effectiveness of Isoniazid Preventive Therapy in HIV-Positive Pregnant Women on Art: An Observational Study using Linked Population Data. Clin Infect Dis. Jan 4 2020.

    142. Mathad JS, Savic R, Britto P, et al. Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women. Clinical Infectious Diseases. 2022;74(9):1604-1613