UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings

Authors
Emily P Hyle, MD
Scott Dryden-Peterson, MD
Section Editor
John A Bartlett, MD
Deputy Editor
Allyson Bloom, MD

INTRODUCTION

The "3 by 5" initiative, launched by United Nations (UN) AIDS and World Health Organization (WHO) in 2003, was a global strategy to provide antiretroviral therapy (ART) to three million people living with HIV/AIDS in 50 developing countries by the end of 2005. Scale-up of services has been expansive, and UNAIDS now estimates that almost 17 million HIV-infected persons were receiving ART at the end of 2015 [1]. Additionally, reductions in new HIV cases, AIDS-related deaths, and overall mortality have been related to expanded access to ART [2]. Despite these achievements, too many patients eligible for ART by WHO criteria are not receiving it, inspiring the latest UNAIDS initiative, “90-90-90,” which aims to have 90 percent of people living with HIV/AIDS know their diagnosis, 90 percent of those diagnosed on ART, and 90 percent of those on ART be virologically suppressed by 2020 [3].

The impact of ART on HIV infection in resource-limited settings will be discussed here. The impact of ART in resource-rich settings and general information on the global epidemic are discussed elsewhere. (See "Global epidemiology of HIV infection".)

EPIDEMIOLOGY OF HIV

Of the estimated 37 million individuals with HIV infection worldwide in 2015, 26million are in sub-Saharan Africa, where the overall prevalence is approximately 5 percent [1,4]. In some African countries, the prevalence exceeds 20 percent. More than half of the HIV-infected population in sub-Saharan Africa is women and children. The HIV prevalence in Southeast Asia is substantially lower (0.6 percent), representing approximately four million HIV-infected people living in this under-resourced region. In Latin America and the Caribbean, infection rates vary by region, with estimated prevalences ranging from 0.5 to 2 percent. Markedly high rates of infection exist within certain risk groups, such as men who have sex with men, prisoners, commercial sex workers, and injection drug users. The global epidemiology of HIV is discussed in detail elsewhere. (See "Global epidemiology of HIV infection", section on 'Worldwide statistics'.)

RECOMMENDATIONS FROM THE WORLD HEALTH ORGANIZATION

Initiation of antiretroviral therapy — In 2015, the World Health Organization (WHO) revised longstanding guidance to withhold treatment until development of immunodeficiency and instead recommended initiation of antiretroviral (ART) for all HIV-infected patients, regardless of CD4 cell count or clinical stage [5]. Those with advanced HIV disease (clinical stage 3 or 4 disease (table 1)) or a CD4 cell count of ≤350 cells/microL are a priority for ART initiation. WHO guidelines also specify a single preferred first-line regimen of tenofovir, lamivudine (or emtricitabine), and efavirenz for all HIV-infected adults who initiate ART, including pregnant and breastfeeding women [5]. This regimen was chosen based on its virologic efficacy, safety, and its ability to be used in the setting of TB treatment, liver disease, and pregnancy, thus enabling HIV treatment to be streamlined across different populations.

The rationale for recommending ART initiation for all, even for those with high CD4 cell counts includes:

                                      

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Fri Jun 24 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. UNAIDS. Global AIDS update: 2016. http://www.unaids.org/sites/default/files/media_asset/global-AIDS-update-2016_en.pdf (Accessed on June 22, 2016).
  2. Bendavid E, Holmes CB, Bhattacharya J, Miller G. HIV development assistance and adult mortality in Africa. JAMA 2012; 307:2060.
  3. UNAIDS. 90–90–90 - An ambitious treatment target to help end the aids epidemic http://www.unaids.org/en/resources/documents/2014/90-90-90 (Accessed on June 22, 2016).
  4. Joint United Nations Programme on HIV/AIDS. The Gap Report. September 2014 http://www.unaids.org/sites/default/files/media_asset/UNAIDS_Gap_report_en.pdf (Accessed on May 20, 2015).
  5. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. http://www.who.int/hiv/pub/arv/arv-2016/en/ (Accessed on June 22, 2016).
  6. Paton NI, Kityo C, Hoppe A, et al. Assessment of second-line antiretroviral regimens for HIV therapy in Africa. N Engl J Med 2014; 371:234.
  7. Date AA, Vitoria M, Granich R, et al. Implementation of co-trimoxazole prophylaxis and isoniazid preventive therapy for people living with HIV. Bull World Health Organ 2010; 88:253.
  8. Braitstein P, Brinkhof MW, Dabis F, et al. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006; 367:817.
  9. Hammond R, Harry TC. Efficacy of antiretroviral therapy in Africa: effect on immunological and virological outcome measures -- a meta-analysis. Int J STD AIDS 2008; 19:291.
  10. Mills EJ, Bakanda C, Birungi J, et al. Life expectancy of persons receiving combination antiretroviral therapy in low-income countries: a cohort analysis from Uganda. Ann Intern Med 2011; 155:209.
  11. Mills EJ, Bakanda C, Birungi J, et al. Mortality by baseline CD4 cell count among HIV patients initiating antiretroviral therapy: evidence from a large cohort in Uganda. AIDS 2011; 25:851.
  12. Severe P, Juste MA, Ambroise A, et al. Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N Engl J Med 2010; 363:257.
  13. Toure S, Kouadio B, Seyler C, et al. Rapid scaling-up of antiretroviral therapy in 10,000 adults in Côte d'Ivoire: 2-year outcomes and determinants. AIDS 2008; 22:873.
  14. Madec Y, Laureillard D, Pinoges L, et al. Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia. AIDS 2007; 21:351.
  15. Egger M, May M, Chêne G, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 2002; 360:119.
  16. Hargrove JW, Humphrey JH, ZVITAMBO Study Group. Mortality among HIV-positive postpartum women with high CD4 cell counts in Zimbabwe. AIDS 2010; 24:F11.
  17. Stringer JS, Zulu I, Levy J, et al. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA 2006; 296:782.
  18. Lawn SD, Harries AD, Anglaret X, et al. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS 2008; 22:1897.
  19. Walker AS, Prendergast AJ, Mugyenyi P, et al. Mortality in the year following antiretroviral therapy initiation in HIV-infected adults and children in Uganda and Zimbabwe. Clin Infect Dis 2012; 55:1707.
  20. Gupta A, Nadkarni G, Yang WT, et al. Early mortality in adults initiating antiretroviral therapy (ART) in low- and middle-income countries (LMIC): a systematic review and meta-analysis. PLoS One 2011; 6:e28691.
  21. Karcher H, Omondi A, Odera J, et al. Risk factors for treatment denial and loss to follow-up in an antiretroviral treatment cohort in Kenya. Trop Med Int Health 2007; 12:687.
  22. Johannessen A, Naman E, Ngowi BJ, et al. Predictors of mortality in HIV-infected patients starting antiretroviral therapy in a rural hospital in Tanzania. BMC Infect Dis 2008; 8:52.
  23. Boulle A, Bock P, Osler M, et al. Antiretroviral therapy and early mortality in South Africa. Bull World Health Organ 2008; 86:678.
  24. Fox MP, Sanne IM, Conradie F, et al. Initiating patients on antiretroviral therapy at CD4 cell counts above 200 cells/microl is associated with improved treatment outcomes in South Africa. AIDS 2010; 24:2041.
  25. TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, et al. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med 2015; 373:808.
  26. Nash D, Katyal M, Brinkhof MW, et al. Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies. AIDS 2008; 22:2291.
  27. INSIGHT START Study Group, Lundgren JD, Babiker AG, et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med 2015; 373:795.
  28. Hoffmann CJ, Fielding KL, Johnston V, et al. Changing predictors of mortality over time from cART start: implications for care. J Acquir Immune Defic Syndr 2011; 58:269.
  29. Bor J, Herbst AJ, Newell ML, Bärnighausen T. Increases in adult life expectancy in rural South Africa: valuing the scale-up of HIV treatment. Science 2013; 339:961.
  30. Cornell M, Schomaker M, Garone DB, et al. Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study. PLoS Med 2012; 9:e1001304.
  31. Dou Z, Xu J, Jiao JH, et al. Gender difference in 2-year mortality and immunological response to ART in an HIV-infected Chinese population, 2006-2008. PLoS One 2011; 6:e22707.
  32. Druyts E, Dybul M, Kanters S, et al. Male sex and the risk of mortality among individuals enrolled in antiretroviral therapy programs in Africa: a systematic review and meta-analysis. AIDS 2013; 27:417.
  33. Pujades-Rodríguez M, Balkan S, Arnould L, et al. Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries. JAMA 2010; 304:303.
  34. Fox MP, Ive P, Long L, et al. High rates of survival, immune reconstitution, and virologic suppression on second-line antiretroviral therapy in South Africa. J Acquir Immune Defic Syndr 2010; 53:500.
  35. Win MM, Maek-A-Nantawat W, Phonrat B, et al. Virologic and Immunologic Outcomes of the Second-Line Regimens of Antiretroviral Therapy Among HIV-Infected Patients in Thailand. J Int Assoc Physicians AIDS Care (Chic) 2011; 10:57.
  36. Murphy RA, Sunpath H, Castilla C, et al. Second-line antiretroviral therapy: long-term outcomes in South Africa. J Acquir Immune Defic Syndr 2012; 61:158.
  37. Bartlett JA, Ribaudo HJ, Wallis CL, et al. Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings. AIDS 2012; 26:1345.
  38. Levison JH, Orrell C, Gallien S, et al. Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa. PLoS One 2012; 7:e32144.
  39. Wood R, Middelkoop K, Myer L, et al. Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control. Am J Respir Crit Care Med 2007; 175:87.
  40. Bassett IV, Wang B, Chetty S, et al. Intensive tuberculosis screening for HIV-infected patients starting antiretroviral therapy in Durban, South Africa. Clin Infect Dis 2010; 51:823.
  41. Oni T, Burke R, Tsekela R, et al. High prevalence of subclinical tuberculosis in HIV-1-infected persons without advanced immunodeficiency: implications for TB screening. Thorax 2011; 66:669.
  42. Koenig SP, Riviere C, Leger P, et al. High mortality among patients with AIDS who received a diagnosis of tuberculosis in the first 3 months of antiretroviral therapy. Clin Infect Dis 2009; 48:829.
  43. Kranzer K, Houben RM, Glynn JR, et al. Yield of HIV-associated tuberculosis during intensified case finding in resource-limited settings: a systematic review and meta-analysis. Lancet Infect Dis 2010; 10:93.
  44. Badri M, Wilson D, Wood R. Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study. Lancet 2002; 359:2059.
  45. Golub JE, Saraceni V, Cavalcante SC, et al. The impact of antiretroviral therapy and isoniazid preventive therapy on tuberculosis incidence in HIV-infected patients in Rio de Janeiro, Brazil. AIDS 2007; 21:1441.
  46. Moore D, Liechty C, Ekwaru P, et al. Prevalence, incidence and mortality associated with tuberculosis in HIV-infected patients initiating antiretroviral therapy in rural Uganda. AIDS 2007; 21:713.
  47. Sanguanwongse N, Cain KP, Suriya P, et al. Antiretroviral therapy for HIV-infected tuberculosis patients saves lives but needs to be used more frequently in Thailand. J Acquir Immune Defic Syndr 2008; 48:181.
  48. El-Sadr WM, Tsiouris SJ. HIV-associated tuberculosis: diagnostic and treatment challenges. Semin Respir Crit Care Med 2008; 29:525.
  49. Lawn SD, Myer L, Bekker LG, Wood R. Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa. AIDS 2007; 21:335.
  50. Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med 2010; 362:697.
  51. Blanc FX, Sok T, Laureillard D, et al. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med 2011; 365:1471.
  52. Havlir DV, Kendall MA, Ive P, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med 2011; 365:1482.
  53. Török ME, Yen NT, Chau TT, et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis. Clin Infect Dis 2011; 52:1374.
  54. Francesconi P, Fabiani M, Dente MG, et al. HIV, malaria parasites, and acute febrile episodes in Ugandan adults: a case-control study. AIDS 2001; 15:2445.
  55. Whitworth J, Morgan D, Quigley M, et al. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet 2000; 356:1051.
  56. French N, Nakiyingi J, Lugada E, et al. Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults. AIDS 2001; 15:899.
  57. Mermin J, Ekwaru JP, Liechty CA, et al. Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study. Lancet 2006; 367:1256.
  58. Jongwutiwes U, Kiertiburanakul S, Sungkanuparph S. Impact of antiretroviral therapy on the relapse of cryptococcosis and survival of HIV-infected patients with cryptococcal infection. Curr HIV Res 2007; 5:355.
  59. Bisson GP, Nthobatsong R, Thakur R, et al. The use of HAART is associated with decreased risk of death during initial treatment of cryptococcal meningitis in adults in Botswana. J Acquir Immune Defic Syndr 2008; 49:227.
  60. Jarvis JN, Meintjes G, Harrison TS. Outcomes of cryptococcal meningitis in antiretroviral naïve and experienced patients in South Africa. J Infect 2010; 60:496.
  61. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis 2010; 50:291.
  62. Müller M, Wandel S, Colebunders R, et al. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis. Lancet Infect Dis 2010; 10:251.
  63. Law WP, Duncombe CJ, Mahanontharit A, et al. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort. AIDS 2004; 18:1169.
  64. Idoko J, Meloni S, Muazu M, et al. Impact of hepatitis B virus infection on human immunodeficiency virus response to antiretroviral therapy in Nigeria. Clin Infect Dis 2009; 49:1268.
  65. Hoffmann CJ, Charalambous S, Martin DJ, et al. Hepatitis B virus infection and response to antiretroviral therapy (ART) in a South African ART program. Clin Infect Dis 2008; 47:1479.
  66. Moore E, Beadsworth MB, Chaponda M, et al. Favourable one-year ART outcomes in adult Malawians with hepatitis B and C co-infection. J Infect 2010; 61:155.
  67. Soriano V, Puoti M, Garcia-Gascó P, et al. Antiretroviral drugs and liver injury. AIDS 2008; 22:1.
  68. Wolday D, Akuffo H, Demissie A, Britton S. Role of Leishmania donovani and its lipophosphoglycan in CD4+ T-cell activation-induced human immunodeficiency virus replication. Infect Immun 1999; 67:5258.
  69. ter Horst R, Collin SM, Ritmeijer K, et al. Concordant HIV infection and visceral leishmaniasis in Ethiopia: the influence of antiretroviral treatment and other factors on outcome. Clin Infect Dis 2008; 46:1702.
  70. Piot P, Quinn TC, Taelman H, et al. Acquired immunodeficiency syndrome in a heterosexual population in Zaire. Lancet 1984; 2:65.
  71. Serwadda D, Mugerwa RD, Sewankambo NK, et al. Slim disease: a new disease in Uganda and its association with HTLV-III infection. Lancet 1985; 2:849.
  72. Casper C. The increasing burden of HIV-associated malignancies in resource-limited regions. Annu Rev Med 2011; 62:157.
  73. Mbulaiteye SM, Katabira ET, Wabinga H, et al. Spectrum of cancers among HIV-infected persons in Africa: the Uganda AIDS-Cancer Registry Match Study. Int J Cancer 2006; 118:985.
  74. Dryden-Peterson S, Medhin H, Kebabonye-Pusoentsi M, et al. Cancer Incidence following Expansion of HIV Treatment in Botswana. PLoS One 2015; 10:e0135602.
  75. Mutyaba I, Phipps W, Krantz EM, et al. A Population-Level Evaluation of the Effect of Antiretroviral Therapy on Cancer Incidence in Kyadondo County, Uganda, 1999-2008. J Acquir Immune Defic Syndr 2015; 69:481.
  76. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011; 365:493.
  77. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007; 369:657.
  78. Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 2010; 375:2092.
  79. Attia S, Egger M, Müller M, et al. Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. AIDS 2009; 23:1397.
  80. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363:2587.
  81. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012; 367:399.
  82. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012; 367:423.
  83. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2013; 381:2083.
  84. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med 2012; 367:411.
  85. Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women. N Engl J Med 2016.
  86. Hallett TB, Baeten JM, Heffron R, et al. Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study. PLoS Med 2011; 8:e1001123.
  87. Walensky RP, Park JE, Wood R, et al. The cost-effectiveness of pre-exposure prophylaxis for HIV infection in South African women. Clin Infect Dis 2012; 54:1504.
  88. Freedberg KA, Kumarasamy N, Losina E, et al. Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy. AIDS 2007; 21 Suppl 4:S117.
  89. Goldie SJ, Yazdanpanah Y, Losina E, et al. Cost-effectiveness of HIV treatment in resource-poor settings--the case of Côte d'Ivoire. N Engl J Med 2006; 355:1141.
  90. Walensky RP, Wolf LL, Wood R, et al. When to start antiretroviral therapy in resource-limited settings. Ann Intern Med 2009; 151:157.
  91. Walensky RP, Ross EL, Kumarasamy N, et al. Cost-effectiveness of HIV treatment as prevention in serodiscordant couples. N Engl J Med 2013; 369:1715.
  92. Walensky RP, Borre ED, Bekker LG, et al. The Anticipated Clinical and Economic Effects of 90-90-90 in South Africa. Ann Intern Med 2016; 165:325.
  93. Moore DM, Awor A, Downing R, et al. CD4+ T-cell count monitoring does not accurately identify HIV-infected adults with virologic failure receiving antiretroviral therapy. J Acquir Immune Defic Syndr 2008; 49:477.
  94. Phillips AN, Pillay D, Miners AH, et al. Outcomes from monitoring of patients on antiretroviral therapy in resource-limited settings with viral load, CD4 cell count, or clinical observation alone: a computer simulation model. Lancet 2008; 371:1443.
  95. Working Group on Modelling of Antiretroviral Therapy Monitoring Strategies in Sub-Saharan Africa, Phillips A, Shroufi A, et al. Sustainable HIV treatment in Africa through viral-load-informed differentiated care. Nature 2015; 528:S68.
  96. Subbaraman R, Chaguturu SK, Mayer KH, et al. Adverse effects of highly active antiretroviral therapy in developing countries. Clin Infect Dis 2007; 45:1093.
  97. DART Trial Team, Mugyenyi P, Walker AS, et al. Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial. Lancet 2010; 375:123.
  98. Koenig SP, Schackman BR, Riviere C, et al. Clinical impact and cost of monitoring for asymptomatic laboratory abnormalities among patients receiving antiretroviral therapy in a resource-poor setting. Clin Infect Dis 2010; 51:600.
  99. Bendavid E, Young SD, Katzenstein DA, et al. Cost-effectiveness of HIV monitoring strategies in resource-limited settings: a southern African analysis. Arch Intern Med 2008; 168:1910.
  100. Bishai D, Colchero A, Durack DT. The cost effectiveness of antiretroviral treatment strategies in resource-limited settings. AIDS 2007; 21:1333.
  101. Vijayaraghavan A, Efrusy MB, Mazonson PD, et al. Cost-effectiveness of alternative strategies for initiating and monitoring highly active antiretroviral therapy in the developing world. J Acquir Immune Defic Syndr 2007; 46:91.
  102. Kimmel AD, Weinstein MC, Anglaret X, et al. Laboratory monitoring to guide switching antiretroviral therapy in resource-limited settings: clinical benefits and cost-effectiveness. J Acquir Immune Defic Syndr 2010; 54:258.
  103. Kahn JG, Marseille E, Moore D, et al. CD4 cell count and viral load monitoring in patients undergoing antiretroviral therapy in Uganda: cost effectiveness study. BMJ 2011; 343:d6884.
  104. Walensky RP, Ciaranello AL, Park JE, Freedberg KA. Cost-effectiveness of laboratory monitoring in sub-Saharan Africa: a review of the current literature. Clin Infect Dis 2010; 51:85.
  105. Levison JH, Wood R, Scott CA, et al. The clinical and economic impact of genotype testing at first-line antiretroviral therapy failure for HIV-infected patients in South Africa. Clin Infect Dis 2013; 56:587.
  106. Holmes CB, Wood R, Badri M, et al. CD4 decline and incidence of opportunistic infections in Cape Town, South Africa: implications for prophylaxis and treatment. J Acquir Immune Defic Syndr 2006; 42:464.
  107. Wiktor SZ, Sassan-Morokro M, Grant AD, et al. Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial. Lancet 1999; 353:1469.
  108. Anglaret X, Chêne G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 1999; 353:1463.
  109. Hamel MJ, Greene C, Chiller T, et al. Does cotrimoxazole prophylaxis for the prevention of HIV-associated opportunistic infections select for resistant pathogens in Kenyan adults? Am J Trop Med Hyg 2008; 79:320.
  110. Mermin J, Lule J, Ekwaru JP, et al. Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and mortality among HIV-uninfected family members. AIDS 2005; 19:1035.
  111. Mermin J, Lule J, Ekwaru JP, et al. Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. Lancet 2004; 364:1428.
  112. Hoffmann CJ, Fielding KL, Charalambous S, et al. Reducing mortality with cotrimoxazole preventive therapy at initiation of antiretroviral therapy in South Africa. AIDS 2010; 24:1709.
  113. Walker AS, Ford D, Gilks CF, et al. Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort. Lancet 2010; 375:1278.
  114. Pitter C, Kahn JG, Marseille E, et al. Cost-effectiveness of cotrimoxazole prophylaxis among persons with HIV in Uganda. J Acquir Immune Defic Syndr 2007; 44:336.
  115. Yazdanpanah Y, Losina E, Anglaret X, et al. Clinical impact and cost-effectiveness of co-trimoxazole prophylaxis in patients with HIV/AIDS in Côte d'Ivoire: a trial-based analysis. AIDS 2005; 19:1299.
  116. Malamba S, Sandison T, Lule J, et al. Plasmodium falciparum dihydrofolate reductase and dihyropteroate synthase mutations and the use of trimethoprim-sulfamethoxazole prophylaxis among persons infected with human immunodeficiency virus. Am J Trop Med Hyg 2010; 82:766.
  117. Sibanda EL, Weller IV, Hakim JG, Cowan FM. Does trimethoprim-sulfamethoxazole prophylaxis for HIV induce bacterial resistance to other antibiotic classes? Results of a systematic review. Clin Infect Dis 2011; 52:1184.
  118. Muyingo SK, Walker AS, Reid A, et al. Patterns of individual and population-level adherence to antiretroviral therapy and risk factors for poor adherence in the first year of the DART trial in Uganda and Zimbabwe. J Acquir Immune Defic Syndr 2008; 48:468.
  119. Muwanga A, Easterbrook P, Schaefer, P, et al. Losses to follow-up in a large ART program in Uganda (abstract 840). 15th Conference on Retroviruses and Opportunistic Infections. 2008. Boston, MA.
  120. Yu JK, Chen SC, Wang KY, et al. True outcomes for patients on antiretroviral therapy who are "lost to follow-up" in Malawi. Bull World Health Organ 2007; 85:550.
  121. Bassett IV, Walensky RP. Integrating HIV screening into routine health care in resource-limited settings. Clin Infect Dis 2010; 50 Suppl 3:S77.
  122. Siedner MJ, Ng CK, Bassett IV, et al. Trends in CD4 count at presentation to care and treatment initiation in sub-Saharan Africa, 2002-2013: a meta-analysis. Clin Infect Dis 2015; 60:1120.
  123. ART-LINC Collaboration of International Databases to Evaluate AIDS (IeDEA), Keiser O, Anastos K, et al. Antiretroviral therapy in resource-limited settings 1996 to 2006: patient characteristics, treatment regimens and monitoring in sub-Saharan Africa, Asia and Latin America. Trop Med Int Health 2008; 13:870.
  124. Mills EJ, Nachega JB, Buchan I, et al. Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a meta-analysis. JAMA 2006; 296:679.
  125. Geng EH, Odeny TA, Lyamuya R, et al. Retention in Care and Patient-Reported Reasons for Undocumented Transfer or Stopping Care Among HIV-Infected Patients on Antiretroviral Therapy in Eastern Africa: Application of a Sampling-Based Approach. Clin Infect Dis 2016; 62:935.
  126. Ivers LC, Kendrick D, Doucette K. Efficacy of antiretroviral therapy programs in resource-poor settings: a meta-analysis of the published literature. Clin Infect Dis 2005; 41:217.
  127. Geng E, Bangsberg D, Musinguzi N, et al. What becomes of the defaulters? A sampling-based approach to determine outcomes of patients who become lost to follow-up in ART scale-up programs in Africa (abstract 842). 15th Conference on Retroviruses and Opportunistic Infections. 2008. Boston, MA.
  128. Posse M, Meheus F, van Asten H, et al. Barriers to access to antiretroviral treatment in developing countries: a review. Trop Med Int Health 2008; 13:904.
  129. Weiser SD, Tuller DM, Frongillo EA, et al. Food insecurity as a barrier to sustained antiretroviral therapy adherence in Uganda. PLoS One 2010; 5:e10340.
  130. Bassett IV, Wang B, Chetty S, et al. Loss to care and death before antiretroviral therapy in Durban, South Africa. J Acquir Immune Defic Syndr 2009; 51:135.
  131. Brinkhof MW, Dabis F, Myer L, et al. Early loss of HIV-infected patients on potent antiretroviral therapy programmes in lower-income countries. Bull World Health Organ 2008; 86:559.
  132. Amuron B, Namara G, Birungi J, et al. Mortality and loss-to-follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda. BMC Public Health 2009; 9:290.
  133. Fox MP, Rosen S. Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007-2009: systematic review. Trop Med Int Health 2010; 15 Suppl 1:1.
  134. Palombi L, Marazzi MC, Guidotti G, et al. Incidence and predictors of death, retention, and switch to second-line regimens in antiretroviral- treated patients in sub-Saharan African Sites with comprehensive monitoring availability. Clin Infect Dis 2009; 48:115.
  135. Rosen S, Fox MP, Gill CJ. Patient retention in antiretroviral therapy programs in sub-Saharan Africa: a systematic review. PLoS Med 2007; 4:e298.
  136. Wang B, Losina E, Stark R, et al. Loss to follow-up in community clinics in South Africa: role of CD4 count, gender, pregnancy (abstract 841). 15th Conference on Retroviruses and Opportunistic Infections. 2008. Boston, MA.
  137. Geng EH, Glidden DV, Emenyonu N, et al. Tracking a sample of patients lost to follow-up has a major impact on understanding determinants of survival in HIV-infected patients on antiretroviral therapy in Africa. Trop Med Int Health 2010; 15 Suppl 1:63.
  138. Brinkhof MW, Pujades-Rodriguez M, Egger M. Mortality of patients lost to follow-up in antiretroviral treatment programmes in resource-limited settings: systematic review and meta-analysis. PLoS One 2009; 4:e5790.
  139. de Cherif TK, Schoeman JH, Cleary S, et al. Early severe morbidity and resource utilization in South African adults on antiretroviral therapy. BMC Infect Dis 2009; 9:205.
  140. Dalal RP, Macphail C, Mqhayi M, et al. Characteristics and outcomes of adult patients lost to follow-up at an antiretroviral treatment clinic in johannesburg, South Africa. J Acquir Immune Defic Syndr 2008; 47:101.
  141. Losina E, Touré H, Uhler LM, et al. Cost-effectiveness of preventing loss to follow-up in HIV treatment programs: a Côte d'Ivoire appraisal. PLoS Med 2009; 6:e1000173.
  142. Duda SN, Farr AM, Lindegren ML, et al. Characteristics and comprehensiveness of adult HIV care and treatment programmes in Asia-Pacific, sub-Saharan Africa and the Americas: results of a site assessment conducted by the International epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration. J Int AIDS Soc 2014; 17:19045.
  143. Orrell C, Bangsberg DR, Badri M, Wood R. Adherence is not a barrier to successful antiretroviral therapy in South Africa. AIDS 2003; 17:1369.
  144. Ford N, Darder M, Spelman T, et al. Early adherence to antiretroviral medication as a predictor of long-term HIV virological suppression: five-year follow up of an observational cohort. PLoS One 2010; 5:e10460.
  145. World Health Organization. Global action plan for HIV drug resistance 2016-2021. http://www.who.int/hiv/pub/drugresistance/hiv-drug-resistance-brief-2016/en/ (Accessed on June 22, 2016).
  146. Gupta RK, Jordan MR, Sultan BJ, et al. Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis. Lancet 2012; 380:1250.
  147. Barth RE, van der Loeff MF, Schuurman R, et al. Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. Lancet Infect Dis 2010; 10:155.
  148. Orrell C, Walensky RP, Losina E, et al. HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Antivir Ther 2009; 14:523.
  149. Hamers RL, Sigaloff KC, Wensing AM, et al. Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies. Clin Infect Dis 2012; 54:1660.
  150. Murphy RA, Sunpath H, Lu Z, et al. Outcomes after virologic failure of first-line ART in South Africa. AIDS 2010; 24:1007.
  151. Hosseinipour MC, van Oosterhout JJ, Weigel R, et al. The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. AIDS 2009; 23:1127.
  152. Marconi VC, Sunpath H, Lu Z, et al. Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal, South Africa. Clin Infect Dis 2008; 46:1589.
  153. Wallis CL, Aga E, Ribaudo H, et al. Drug susceptibility and resistance mutations after first-line failure in resource limited settings. Clin Infect Dis 2014; 59:706.
  154. TenoRes Study Group. Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Lancet Infect Dis 2016; 16:565.
  155. Granich RM, Gilks CF, Dye C, et al. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet 2009; 373:48.
  156. Walensky RP, Paltiel AD, Losina E, et al. Test and treat DC: forecasting the impact of a comprehensive HIV strategy in Washington DC. Clin Infect Dis 2010; 51:392.
  157. Dodd PJ, Garnett GP, Hallett TB. Examining the promise of HIV elimination by 'test and treat' in hyperendemic settings. AIDS 2010; 24:729.
  158. Holmes CB, Coggin W, Jamieson D, et al. Use of generic antiretroviral agents and cost savings in PEPFAR treatment programs. JAMA 2010; 304:313.
  159. Clinton Health Access. 2015 Antiretroviral (ARV) chai reference price list. http://www.clintonhealthaccess.org/content/uploads/2016/01/2015-CHAI-ARV-Reference-Price-List.pdf (Accessed on June 22, 2016).
  160. Rosen S, Long L, Sanne I, et al. The net cost of incorporating resistance testing into HIV/AIDS treatment in South Africa: a Markov model with primary data. J Int AIDS Soc 2011; 14:24.
  161. No time to quit: HIV/AIDS treatment gap widening in Africa. http://www.doctorswithoutborders.org/publications/reports/2010/MSF-No-Time-to-Quit-HIV-AIDS.pdf (Accessed on October 01, 2011).
  162. Voelker R. One casualty of global economic crisis: uncertain finances for HIV/AIDS programs. JAMA 2010; 304:259.
  163. http://www.pepfar.gov/press/80064.htm (Accessed on October 25, 2012).
  164. Denny CC, Emanuel EJ. US health aid beyond PEPFAR: the Mother & Child Campaign. JAMA 2008; 300:2048.