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Annual Review of Medicine

Volume 71, 2020

Prevention of HIV Transmission and the HPTN 052 Study

Abstract

The HIV Prevention Trials Network 052 study (HPTN 052) was a clinical trial designed to determine whether early treatment for HIV infection prevented transmission of the virus in couples where one partner was infected with HIV and the other was not, referred to as HIV serodiscordant or serodifferent couples. The study enrolled 1,763 couples at 13 sites in 9 countries in Asia, Africa, and the Americas. HPTN 052 demonstrated a minimum of 96% reduction of HIV in heterosexual couples ascribed to antiretroviral treatment; early treatment of HIV significantly reduced other infections in the HIV-infected subjects. This study, in conjunction with similar research, led to significant changes in international HIV treatment guidelines and the concept of treatment as prevention (TasP). This article provides the scientific background and history of how HPTN 052 came into being, the challenges it faced, and the ultimate impact it had on the fields of HIV treatment and prevention.

Keyword(s): antiretroviral therapy, ART, HIV prevention, HIV Prevention Trials Network, HPTN 052, serodiscordant couples, TasP, treatment as prevention, viral suppression
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2020-01-27
2024-04-25
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Literature Cited

  1. 1. 
    Cohen J. 2011. Breakthrough of the year. HIV treatment as prevention. Science 334:1628
     [Google Scholar]
  2. 2. 
    Cohen MS, Chen YQ, McCauley M et al. 2011. Prevention of HIV-1 infection with early antiretroviral therapy. N. Engl. J. Med. 365:493–505
     [Google Scholar]
  3. 3. 
    Cohen MS, Chen YQ, McCauley M et al. 2016. Antiretroviral therapy for the prevention of HIV-1 transmission. N. Engl. J. Med. 375:830–39
     [Google Scholar]
  4. 4. 
    Gottlieb MS, Schanker HM, Fan PT et al. 1981. Pneumocystis pneumonia—Los Angeles. Morb. Mortal. Wkly. Rep. 30:250–52
     [Google Scholar]
  5. 5. 
    Centers for Disease Control (CDC) 1982. Epidemiologic notes and reports: Pneumocystiscarinii pneumonia among persons with hemophilia A. Morb. Mortal. Wkly. Rep. 31:265–367
     [Google Scholar]
  6. 6. 
    White GC 2nd, TJ Matthews, Weinhold KJ et al. 1986. HTLV-III seroconversion associated with heat-treated factor VIII concentrate. Lancet 1:611–12
     [Google Scholar]
  7. 7. 
    Royce RA, Sena A, Cates W Jr., Cohen MS 1997. Sexual transmission of HIV. N. Engl. J. Med. 336:1072–78
     [Google Scholar]
  8. 8. 
    Patel P, Borkowf CB, Brooks JT et al. 2014. Estimating per-act HIV transmission risk: a systematic review. AIDS 28:1509–19
     [Google Scholar]
  9. 9. 
    Centers for Disease Control (CDC) 1983. Current trends update: acquired immunodeficiency syndrome (AIDS)—United States. Morb. Mortal. Wkly. Rep. 32:465–67
     [Google Scholar]
  10. 10. 
    Fischl MA, Richman DD, Grieco MH et al. 1987. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N. Engl. J. Med. 317:185–91
     [Google Scholar]
  11. 11. 
    Parks WP, Parks ES, Fischl MA et al. 1988. HIV-1 inhibition by azidothymidine in a concurrently randomized placebo-controlled trial. J. Acquir. Immune Defic. Syndr. 1:125–30
     [Google Scholar]
  12. 12. 
    Working Group of the Office of AIDS Research Advisory Council (OARAC), Department of Health and Human Services Panel on Antiretroviral Guidelines 2018. AIDSinfo: guidelines for the use of antiretroviral agents in adults and adolescents living with HIV https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf
  13. 13. 
    Samji H, Cescon A, Hogg RS et al. 2013. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLOS ONE 8:e81355
     [Google Scholar]
  14. 14. 
    Connor EM, Sperling RS, Gelber R et al. 1994. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N. Engl. J. Med. 331:1173–80
     [Google Scholar]
  15. 15. 
    Kalichman SC, Di Berto G, Eaton L 2008. Human immunodeficiency virus viral load in blood plasma and semen: review and implications of empirical findings. Sex. Transm. Dis. 35:55–60
     [Google Scholar]
  16. 16. 
    Trezza CR, Kashuba AD. 2014. Pharmacokinetics of antiretrovirals in genital secretions and anatomic sites of HIV transmission: implications for HIV prevention. Clin. Pharmacokinet. 53:611–24
     [Google Scholar]
  17. 17. 
    Galvin SR, Cohen MS. 2004. The role of sexually transmitted diseases in HIV transmission. Nat. Rev. Microbiol. 2:33–42
     [Google Scholar]
  18. 18. 
    Sadiq ST, Taylor S, Kaye S et al. 2002. The effects of antiretroviral therapy on HIV-1 RNA loads in seminal plasma in HIV-positive patients with and without urethritis. AIDS 16:219–25
     [Google Scholar]
  19. 19. 
    Gilliam BL, Dyer JR, Fiscus SA et al. 1997. Effects of reverse transcriptase inhibitor therapy on the HIV-1 viral burden in semen. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 15:54–60
     [Google Scholar]
  20. 20. 
    Quinn TC, Wawer MJ, Sewankambo N et al. 2000. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N. Engl. J. Med. 342:921–29
     [Google Scholar]
  21. 21. 
    Baeten JM, Kahle E, Lingappa JR et al. 2011. Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Sci. Transl. Med. 3:77ra29
     [Google Scholar]
  22. 22. 
    Musicco M, Lazzarin A, Nicolosi A et al. 1994. Antiretroviral treatment of men infected with human immunodeficiency virus type 1 reduces the incidence of heterosexual transmission. Arch. Intern. Med. 154:1971–76
     [Google Scholar]
  23. 23. 
    Muessig KE, Cohen MS. 2014. Advances in HIV prevention for serodiscordant couples. Curr. HIV/AIDS Rep. 11:434–46
     [Google Scholar]
  24. 24. 
    Gulick RM, Ribaudo HJ, Shikuma CM et al. 2004. Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N. Engl. J. Med. 350:1850–61
     [Google Scholar]
  25. 25. 
    Eron JJ, Benoit SL, Jemsek J et al. 1995. Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. N. Engl. J. Med. 333:1662–69
     [Google Scholar]
  26. 26. 
    Carpenter CC, Fischl MA, Hammer SM et al. 1996. Antiretroviral therapy for HIV infection in 1996. Recommendations of an international panel. JAMA 276:146–54
     [Google Scholar]
  27. 27. 
    Ho DD. 1995. Time to hit HIV, early and hard. N. Engl. J. Med. 333:450–51
     [Google Scholar]
  28. 28. 
    Dowell W. 1999. Ethics and AIDS drugs. Time 154:49
     [Google Scholar]
  29. 29. 
    Ramo JC. 2001. The real price of fighting AIDS. Time 158:35
     [Google Scholar]
  30. 30. 
    Eyawo O, de Walque D, Ford N et al. 2010. HIV status in discordant couples in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Infect. Dis. 10:770–77
     [Google Scholar]
  31. 31. 
    Dunkle KL, Stephenson R, Karita E et al. 2008. New heterosexually transmitted HIV infections in married or cohabiting couples in urban Zambia and Rwanda: an analysis of survey and clinical data. Lancet 371:2183–91
     [Google Scholar]
  32. 32. 
    Simonsen JN, Fowke KR, MacDonald KS, Plummer FA 1998. HIV pathogenesis: mechanisms of susceptibility and disease progression. Curr. Opin. Microbiol. 1:423–29
     [Google Scholar]
  33. 33. 
    Freedman B. 1987. Equipoise and the ethics of clinical research. N. Engl. J. Med. 317:141–45
     [Google Scholar]
  34. 34. 
    Cohen MS, McCauley M, Sugarman J 2012. Establishing HIV treatment as prevention in the HIV Prevention Trials Network 052 randomized trial: an ethical odyssey. Clin. Trials 9:340–47
     [Google Scholar]
  35. 35. 
    Grinsztejn B, Hosseinipour MC, Ribaudo HJ et al. 2014. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial. Lancet Infect. Dis. 14:281–90
     [Google Scholar]
  36. 36. 
    Severe P, Juste MA, Ambroise A et al. 2010. Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N. Engl. J. Med. 363:257–65
     [Google Scholar]
  37. 37. 
    Eshleman SH, Hudelson SE, Redd AD et al. 2011. Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial. J. Infect. Dis. 204:1918–26
     [Google Scholar]
  38. 38. 
    Romero-Severson EO, Bulla I, Leitner T 2016. Phylogenetically resolving epidemiologic linkage. PNAS 113:2690–95
     [Google Scholar]
  39. 39. 
    Rose R, Hall M, Redd AD et al. 2018. Phylogenetic methods inconsistently predict the direction of HIV transmission among heterosexual pairs in the HPTN 052 cohort. J. Infect. Dis. 220:91406–13
     [Google Scholar]
  40. 40. 
    Ping LH, Jabara CB, Rodrigo AG et al. 2013. HIV-1 transmission during early antiretroviral therapy: evaluation of two HIV-1 transmission events in the HPTN 052 prevention study. PLOS ONE 8:e71557
     [Google Scholar]
  41. 41. 
    Celum C, Wald A, Lingappa JR et al. 2010. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N. Engl. J. Med. 362:427–39
     [Google Scholar]
  42. 42. 
    Lundgren JD, Babiker AG, Gordin F et al. 2015. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N. Engl. J. Med. 373:795–807
     [Google Scholar]
  43. 43. 
    Danel C, Moh R, Gabillard D et al. 2015. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N. Engl. J. Med. 373:808–22
     [Google Scholar]
  44. 44. 
    Walensky RP, Ross EL, Kumarasamy N et al. 2013. Cost-effectiveness of HIV treatment as prevention in serodiscordant couples. N. Engl. J. Med. 369:1715–25
     [Google Scholar]
  45. 45. 
    Fauci AS, Redfield RR, Sigounas G et al. 2019. Ending the HIV epidemic: a plan for the United States. JAMA 321:844–45
     [Google Scholar]
  46. 46. 
    Eisinger RW, Dieffenbach CW, Fauci AS 2019. HIV viral load and transmissibility of HIV infection: undetectable equals untransmittable. JAMA 321:451–52
     [Google Scholar]
  47. 47. 
    The Lancet. 2017. U = U taking off in 2017. Editorial. Lancet HIV 4:PE475
     [Google Scholar]
  48. 48. 
    Rodger AJ, Cambiano V, Bruun T et al. 2016. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA 316:171–81
     [Google Scholar]
  49. 49. 
    Rodger A, Cambiano V, Bruun T et al. 2018. Risk of HIV transmission through condomless sex in MSM couples with suppressive ART: the PARTNER2 Study extended results in gay men Presented at the 22nd International AIDS Conference Amsterdam, Netherlands: July 23–27, Abstr 13470
  50. 50. 
    Bavinton BR, Pinto AN, Phanuphak N et al. 2018. Viral suppression and HIV transmission in serodiscordant male couples: an international, prospective, observational, cohort study. Lancet HIV 5:e438–47
     [Google Scholar]
  51. 51. 
    Baeten JM, Donnell D, Ndase P et al. 2012. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 367:399–410
     [Google Scholar]
  52. 52. 
    Grant RM, Lama JR, Anderson PL et al. 2010. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N. Engl. J. Med. 363:2587–99
     [Google Scholar]
  53. 53. 
    Van Damme L, Corneli A, Ahmed K et al. 2012. Preexposure prophylaxis for HIV infection among African women. N. Engl. J. Med. 367:411–22
     [Google Scholar]
  54. 54. 
    Thigpen MC, Kebaabetswe PM, Paxton LA et al. 2012. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N. Engl. J. Med. 367:423–34
     [Google Scholar]
  55. 55. 
    McCormack S, Dunn DT, Desai M et al. 2016. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet 387:53–60
     [Google Scholar]
  56. 56. 
    Molina JM, Cahn P, Grinsztejn B et al. 2011. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet 378:238–46
     [Google Scholar]
  57. 57. 
    Centers for Disease Control and Prevention (CDC), Department of Health and Human Services 2018. Preexposure prophylaxis for the prevention of HIV infection in the United States—2017 update: a clinical practice guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf
  58. 58. 
    Cohen MS, Holmes C, Padian N et al. 2012. HIV treatment as prevention: how scientific discovery occurred and translated rapidly into policy for the global response. Health Aff 31:1439–49
     [Google Scholar]
  59. 59. 
    Joint United Nations Programme on HIV/AIDS (UNAIDS) 2014. 90–90–90: An ambitious treatment target to help end the AIDS epidemic Geneva: UNAIDS https://www.unaids.org/sites/default/files/media_asset/90-90-90_en.pdf
  60. 60. 
    Gardner EM, McLees MP, Steiner JF et al. 2011. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin. Infect. Dis. 52:793–800
     [Google Scholar]
  61. 61. 
    Tanser F, Barnighausen T, Grapsa E et al. 2013. High coverage of ART associated with decline in risk of HIV acquisition in rural KwaZulu-Natal, South Africa. Science 339:966–71
     [Google Scholar]
  62. 62. 
    Havlir D, Charlebois E, Balzer L et al. 2018. SEARCH community cluster randomized study of HIV “test and treat” using multi- disease approach and streamlined care in rural Uganda and Kenya Presented at the 22nd International AIDS Conference Amsterdam, Netherlands: July 23–27, Abstr 3469
  63. 63. 
    Hayes R, Donnell D, Floyd S et al. 2019. Impact of universal testing and treatment in Zambia and South Africa: HPTN 071 (PopART) Presented at the Conference on Retroviruses and Opportunistic Infections (CROI) Seattle, WA: Mar. 4–7, Abstr 92
  64. 64. 
    Shanaube K et al. 2016. Uptake of HIV testing in the HPTN 071 (PopART) trial in Zambia Presented at the Conference on Retroviruses and Opportunistic Infections (CROI) Boston, MA: Feb. 22–25, Abstr. 981
  65. 65. 
    Makhema MJ, Wirth K, Pretorius Holme M et al. 2018. Impact of prevention and treatment interventions on population HIV incidence: primary results of the community-randomized Ya Tsie Botswana prevention project Presented at the 22nd International AIDS Conference Amsterdam, Netherlands: July 23–27
  66. 66. 
    Novitsky V, Wang R, Bussmann H et al. 2010. HIV-1 subtype C-infected individuals maintaining high viral load as potential targets for the “test-and-treat” approach to reduce HIV transmission. PLOS ONE 5:e10148
     [Google Scholar]
  67. 67. 
    Hayes R, Ayles H, Beyers N et al. 2014. HPTN 071 (PopART): rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment—a study protocol for a cluster randomised trial. Trials 15:57
     [Google Scholar]
  68. 68. 
    Zelaya CE, Le Minh N, Lau B et al. 2016. The effect of a multi-level intervention on the initiation of antiretroviral therapy (ART) among HIV-infected men who inject drugs and were diagnosed late in Thai Nguyen, Vietnam. PLOS ONE 11:e0161718
     [Google Scholar]
  69. 69. 
    Justman JE, Mugurungi O, El-Sadr WM 2018. HIV population surveys—bringing precision to the global response. N. Engl. J. Med. 378:1859–61
     [Google Scholar]
  70. 70. 
    Okano JT, Robbins D, Palk L et al. 2016. Testing the hypothesis that treatment can eliminate HIV: a nationwide, population-based study of the Danish HIV epidemic in men who have sex with men. Lancet Infect. Dis. 16:789–96
     [Google Scholar]
  71. 71. 
    Abuelezam NN, McCormick AW, Fussell T et al. 2016. Can the heterosexual HIV epidemic be eliminated in South Africa using combination prevention? A modeling analysis. Am. J. Epidemiol. 184:239–48
     [Google Scholar]
  72. 72. 
    Anderson SJ, Cherutich P, Kilonzo N et al. 2014. Maximising the effect of combination HIV prevention through prioritisation of the people and places in greatest need: a modelling study. Lancet 384:249–56
     [Google Scholar]
  73. 73. 
    Friedland BA, Sprague L, Nyblade L et al. 2018. Measuring intersecting stigma among key populations living with HIV: implementing the People Living with HIV Stigma Index 2.0. J. Int. AIDS Soc. 21:Suppl. 5e25131
     [Google Scholar]
  74. 74. 
    Stockton MA, Giger K, Nyblade L 2018. A scoping review of the role of HIV-related stigma and discrimination in noncommunicable disease care. PLOS ONE 13:e0199602
     [Google Scholar]
  75. 75. 
    Adimora AA, Schoenbach VJ, Taylor EM et al. 2013. Sex ratio, poverty, and concurrent partnerships among men and women in the United States: a multilevel analysis. Ann. Epidemiol. 23:716–19
     [Google Scholar]
  76. 76. 
    Lesko CR, Cole SR, Miller WC et al. 2015. Ten-year survival by race/ethnicity and sex among treated, HIV-infected adults in the United States. Clin. Infect. Dis. 60:1700–7
     [Google Scholar]
  77. 77. 
    Rerks-Ngarm S, Pitisuttithum P, Excler JL et al. 2017. Randomized, double-blind evaluation of late boost strategies for HIV-uninfected vaccine recipients in the RV144 HIV vaccine efficacy trial. J. Infect. Dis. 215:1255–63
     [Google Scholar]
  78. 78. 
    Margolis DA, Gonzalez-Garcia J, Stellbrink HJ et al. 2017. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet 390:1499–510
     [Google Scholar]
  79. 79. 
    Klein F, Mouquet H, Dosenovic P et al. 2013. Antibodies in HIV-1 vaccine development and therapy. Science 341:1199–204
     [Google Scholar]
  80. 80. 
    Margolis DM. 2017. Towards an HIV cure: a view of a developing field. J. Infect. Dis. 215:S109–10
     [Google Scholar]
/content/journals/10.1146/annurev-med-110918-034551
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Prevention of HIV Transmission and the HPTN 052 Study
Annual Review of Medicine 71, 347 (2020); https://doi.org/10.1146/annurev-med-110918-034551
/content/journals/10.1146/annurev-med-110918-034551
/content/journals/10.1146/annurev-med-110918-034551
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