Current HIV/AIDS Reports

, Volume 10, Issue 2, pp 152–158 | Cite as

Antiretroviral Therapy for Prevention Is a Combination Strategy

  • Margaret L. McNairy
  • Myron Cohen
  • Wafaa M. El-Sadr
The Global Epidemic (Q Abdool Karim, Section Editor)


In the past several years, the debate of “treatment vs prevention” has shifted with the introduction of the concept of “treatment as prevention,” (TasP), stemming from a series of compelling observational, ecological, and modeling studies as well as HPTN 052, a randomized clinical trial, demonstrating that use of ART is associated with a decrease in HIV transmission. In addition to TasP being viewed as 1 intervention in a combination strategy for HIV Prevention, TasP is, in and of itself, a combination of multiple interventions that need to be implemented with high coverage in order to achieve its potential impact.


HIV Antiretroviral therapy HIV prevention Treatment as prevention (TasP) Global epidemic Combination intervention 


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Cohen MS, Holmes C, Padian N, Wolf M, Hirnschall G, Lo YR, et al. HIV treatment as prevention: how scientific discovery occurred and translated rapidly into policy for the global response. Health Aff. 2012;31:1439–49.CrossRefGoogle Scholar
  2. 2.
    Marseille E, Hofmann PB, Kahn JG. HIV prevention before HAART in sub-Saharan Africa. Lancet. 2002;359:1851–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Ford N, Calmy A, Mills EJ. The first decade of antiretroviral therapy in Africa. Glob Health. 2011;7:33.CrossRefGoogle Scholar
  4. 4.
    Hogg RS, Heath KV, Yip B, Craib KJ, O'Shaughnessy MV, Schechter MT, et al. Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. JAMA. 1998;279:450–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Nakagawa F, Lodwick RK, Smith CJ, Smith R, Cambiano V, Lundgren JD, et al. Projected life expectancy of people with HIV according to timing of diagnosis. AIDS. 2012;26:335–43.PubMedCrossRefGoogle Scholar
  6. 6.
    WHO UNAIDS UNICEF. Global HIV/AIDS Response, epidemic update and health sector progress torwards universal access-progress report. 2011. In: Geneva; 2011. Accessed 10 Dec 2012.
  7. 7.
  8. 8.
    • Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493–505. A multicountry, randomized controlled trial of early vs delayed ART in HIV-positive persons with CD4+ cell count between 350–550 cells/mm 3 , showing a 96 % reduction in HIV transmission in serodiscordant heterosexual couples in which the HIV -positive partner received early therapy.Google Scholar
  9. 9.
    • Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet. 2009;373:48–57. A modeling study illustrating that the theroretical strategy of universal voluntary HIV testing coupled with immediate ART treatment (TasP) could lead to HIV elimination in South Africa.Google Scholar
  10. 10.
    Charlebois ED, Das M, Porco TC, Havlir DV. The effect of expanded antiretroviral treatment strategies on the HIV epidemic among men who have sex with men in San Francisco. Clin Infect Dis. 2011;52:1046–9.PubMedCrossRefGoogle Scholar
  11. 11.
    • Powers KA, Ghani AC, Miller WC, Hoffman IF, Pettifor AE, Kamanga G, et al. The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: a modelling study. Lancet. 2011;378:256–68. A modeling study evaluating the contribution of early acute HIV infection on HIV incidence in Malawi found that 38.4 % of HIV transmission could be attributable to sexual contact with individuals with early infection. The study suggests that HIV prevention interventions must target both chronic and acute infection in this sub-Saharan African setting.Google Scholar
  12. 12.
    Das M, Chu PL, Santos GM, Scheer S, Vittinghoff E, McFarland W, et al. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS One. 2010;5:e11068.PubMedCrossRefGoogle Scholar
  13. 13.
    Montaner JS, Lima VD, Barrios R, Yip B, Wood E, Kerr T, et al. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study. Lancet. 2010;376:532–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Dieffenbach CW, Fauci AS. Universal voluntary testing and treatment for prevention of HIV transmission. JAMA. 2009;301:2380–2.PubMedCrossRefGoogle Scholar
  15. 15.
    Dodd PJ, Garnett GP, Hallett TB. Examining the promise of HIV elimination by ‘test and treat’ in hyperendemic settings. AIDS. 2010;24:729–35.PubMedCrossRefGoogle Scholar
  16. 16.
    Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med. 2005;2:e298.PubMedCrossRefGoogle Scholar
  17. 17.
    Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomized controlled trial. Lancet. 2007;369:643–56.PubMedCrossRefGoogle Scholar
  18. 18.
    Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomized trial. Lancet. 2007;369:657–66.PubMedCrossRefGoogle Scholar
  19. 19.
    Paltiel AD, Walensky RP, Schackman BR, Seage 3rd GR, Mercincavage LM, Weinstein MC, et al. Expanded HIV screening in the United States: effect on clinical outcomes, HIV transmission, and costs. Ann Intern Med. 2006;145:797–806.PubMedCrossRefGoogle Scholar
  20. 20.
    Cooper ER, Charurat M, Mofenson L, Hanson IC, Pitt J, Diaz C, et al. Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr. 2002;29:484–94.PubMedGoogle Scholar
  21. 21.
    Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587–99.PubMedCrossRefGoogle Scholar
  22. 22.
    Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010;329:1168–74.PubMedCrossRefGoogle Scholar
  23. 23.
    • Hull MW, Wu Z, Montaner JS. Optimizing the engagement of care cascade: a critical step to maximize the impact of HIV treatment as prevention. Curr Opin HIV AIDS. 2012;7:579–86. A review article which discusses treatment as prevention in the framework of “Seek, Test, Treat and Retain,” with each step in the framework essential for optimization of ART as an effective HIV prevention strategy.Google Scholar
  24. 24.
    Eaton JW, Johnson LF, Salomon JA, Barnighausen T, Bendavid E, Bershteyn A, et al. HIV treatment as prevention: systematic comparison of mathematical models of the potential impact of antiretroviral therapy on HIV incidence in South Africa. PLoS Med. 2012;9:e1001245.PubMedCrossRefGoogle Scholar
  25. 25.
    • Rosen S, Fox MP. Retention in HIV care between testing and treatment in sub-Saharan Africa: a systematic review. PLoS Med. 2011;8:e1001056. A review article summarizing linkage and pre-ART retention across 28 studies in Africa. The median proportion of patient retained from HIV testing to receipt of CD4 count results or clinical stage (ie, linkage to care) was 59 % (35 %–8 %), from staging to ART eligiblity was 46 % (31 %–95 %) and from ART eligiblity to ART initiation was 68 % (14 %–84 %). Majority of studies only reported 1 category.Google Scholar
  26. 26.
    Fox MP, Rosen S. Patient retention in antiretroviral therapy programs up to three years on treatment in sub Saharan Africa, 2007–2009: systematic review. Tropical Med Int Health. 2010;15:1–15.CrossRefGoogle Scholar
  27. 27.
    • Mugglin C, Estill J, Wandeler G, Bender N, Egger M, Gsponer T, et al. Loss to program between HIV diagnosis and initiation of antiretroviral therapy in sub-Saharan Africa: systematic review and meta-analysis. Trop Med Int Health. 2012. doi:10.1111/j.1365-3156.2012.03089.x. A review or 29 studies from sub-Saharan Africa including 148,912 patients which reports of 100 patients with an HIV positive test, 72 % have a CD4 cell count measurement, 40 % were eligible for ART and 25 % initiated ART.
  28. 28.
    • Vital signs: HIV prevention through care and treatment--United States. MMWR Morb Mortal Wkly Rep. 2011;60:1618–23. Using 2010 surveillence data, this study estimates that 28 % of HIV-infected persons in the United States have viral load suppression. Google Scholar
  29. 29.
    • Gardner EM, McLees MP, Steiner JF, Del Rio C, Burman WJ. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis. 2011;52:793–800. A review illustrating that only small improvements in the magnitude of viral load suppression are achieved when 1 step in the HIV care continuum is improved; however, when all steps are improved to greater than 90 % fidelity, viral load suppression increased from 19 % to 66 %.Google Scholar
  30. 30.
    Marks G, Gardner LI, Craw J, Giordano TP, Mugavero MJ, Keruly JC, et al. The spectrum of engagement in HIV care: do more than 19 % of HIV-infected persons in the US have undetectable viral load? Clin Infect Dis. 2011;53:1168–9. author’s reply 1169–70.PubMedCrossRefGoogle Scholar
  31. 31.
    Andrews JR, Wood R, Bekker LG, Middelkoop K, Walensky RP. Projecting the benefits of antiretroviral therapy for HIV prevention: the impact of population mobility and linkage to care. J Infect Dis. 2012;206:543–51.PubMedCrossRefGoogle Scholar
  32. 32.
    Anglaret X, Scott CA, Walensky RP, Ouattara E, Losina E, Moh R, et al. Could early antiretroviral therapy entail more risks than benefits in sub-Saharan African HIV-infected adults? A model-based analysis. Antivir Ther. 2012. doi:10.3851/IMP2231.
  33. 33.
  34. 34.
    Branson BM, Handsfield HH, Lampe MA, Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55:1–17. quiz CE11–4.PubMedGoogle Scholar
  35. 35.
    WHO. Antiretroviral therapy for HIV infection in infants and children: towards universal access. In. Geneva; 2010.Google Scholar
  36. 36.
    Sekandi JN, Sempeera H, List J, Mugerwa MA, Asiimwe S, Yin X, et al. High acceptance of home-based HIV counseling and testing in an urban community setting in Uganda. BMC Publ Health. 2011;11:730.CrossRefGoogle Scholar
  37. 37.
    Molesworth AM, Ndhlovu R, Banda E, Saul J, Ngwira B, Glynn JR, et al. High accuracy of home-based community rapid HIV testing in rural Malawi. J Acquir Immune Defic Syndr. 2010;55:625–30.PubMedCrossRefGoogle Scholar
  38. 38.
    Tumwesigye E, Wana G, Kasasa S, Muganzi E, Nuwaha F. High uptake of home-based, district-wide, HIV counseling and testing in Uganda. AIDS Patient Care STDS. 2010;24:735–41.PubMedCrossRefGoogle Scholar
  39. 39.
    Choko AT, Desmond N, Webb EL, Chavula K, Napierala-Mavedzenge S, Gaydos CA, et al. The uptake and accuracy of oral kits for HIV self-testing in high HIV prevalence setting: a cross-sectional feasibility study in Blantyre, Malawi. PLoS Med. 2011;8:e1001102.PubMedCrossRefGoogle Scholar
  40. 40.
    Kharsany AB, Karim QA, Karim SS. Uptake of provider-initiated HIV testing and counseling among women attending an urban sexually transmitted disease clinic in South Africa - missed opportunities for early diagnosis of HIV infection. AIDS Care. 2010;22:533–7.PubMedCrossRefGoogle Scholar
  41. 41.
    MacPherson P, Lalloo DG, Choko AT, Mann GH, Squire SB, Mwale D, et al. Suboptimal patterns of provider initiated HIV testing and counselling, antiretroviral therapy eligibility assessment and referral in primary health clinic attendees in Blantyre, Malawi. Trop Med Int Health. 2012;17:507–17.PubMedCrossRefGoogle Scholar
  42. 42.
    Marks G, Gardner LI, Craw J, Crepaz N. Entry and retention in medical care among HIV-diagnosed persons: a meta-analysis. AIDS. 2010;24:2665–78.PubMedCrossRefGoogle Scholar
  43. 43.
    • Thompson MA, Mugavero MJ, Amico KR, Cargill VA, Chang LW, Gross R, et al. Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: evidence-based recommendations from an International Association of Physicians in AIDS Care. panel. Ann Intern Med. 2012;156:817–33. 2012 guidelines from the International Assocaition of Physicians in AIDS Care. based on review of 325 randomized, controlled trails and observational studies on linkage to care, retention in care, and ART adherence.Google Scholar
  44. 44.
    • Govindasamy D, Ford N, Kranzer K. Risk factors, barriers and facilitators for linkage to antiretroviral therapy care: a systematic review. AIDS. 2012;26:2059–67. The first systematic review of risk factors for poor linkage to ART care. Common barriers are transport/distance to clinic, stigma, and disclosure and suboptimal clinic operations.Google Scholar
  45. 45.
    Christopoulos KA, Das M, Colfax GN. Linkage and retention in HIV care among men who have sex with men in the United States. Clin Infect Dis. 2011;52 Suppl 2:S214–22.PubMedCrossRefGoogle Scholar
  46. 46.
    Paterson DL, Swindells S, Mohr J, Brester M, Vergis EN, Squier C, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000;133:21–30.PubMedCrossRefGoogle Scholar
  47. 47.
    Kelly JA, Otto-Salaj LL, Sikkema KJ, Pinkerton SD, Bloom FR. Implications of HIV treatment advances for behavioral research on AIDS: protease inhibitors and new challenges in HIV secondary prevention. Health Psychol. 1998;17:310–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Crepaz N, Hart TA, Marks G. Highly active antiretroviral therapy and sexual risk behavior: a meta-analytic review. JAMA. 2004;292:224–36.PubMedCrossRefGoogle Scholar
  49. 49.
    Ostrow DE, Fox KJ, Chmiel JS, Silvestre A, Visscher BR, Vanable PA, et al. Attitudes towards highly active antiretroviral therapy are associated with sexual risk taking among HIV-infected and uninfected homosexual men. AIDS. 2002;16:775–80.PubMedCrossRefGoogle Scholar
  50. 50.
    Losina E, Bassett IV, Giddy J, Chetty S, Regan S, Walensky RP, et al. The “ART” of linkage: pre-treatment loss to care after HIV diagnosis at 2 PEPFAR sites in Durban, South Africa. PLoS One. 2010;5:e9538.PubMedCrossRefGoogle Scholar
  51. 51.
    Larson BA, Brennan A, McNamara L, Long L, Rosen S, Sanne I, et al. Early loss to follow up after enrolment in pre-ART care at a large public clinic in Johannesburg, South Africa. Trop Med Int Health. 2010;15 Suppl 1:43–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Kovacs SM. Mfaume J, Sabatier H, Nuwagaba-Biribonwoha M, Lamb G, Arthur A, et al. The identification of high levels of loss to follow-up (LTFU) among pre-ART patients with unknown ART eligibility in 5 regions of Tanzania. In: IAS. Washington, DC; 2012.Google Scholar
  53. 53.
    El-Sadr WM, Coburn BJ, Blower S. Modeling the impact on the HIV epidemic of treating discordant couples with antiretrovirals to prevent transmission. AIDS. 2011;25:2295–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Ulett KB, Willig JH, Lin HY, Routman JS, Abroms S, Allison J, et al. The therapeutic implications of timely linkage and early retention in HIV care. AIDS Patient Care STDS. 2009;23:41–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Kahn TR, Desmond M, Rao D, Marx GE, Guthrie BL, Bosire R, et al. Delayed initiation of antiretroviral therapy among HIV-discordant couples in Kenya. AIDS Care. 2012. doi:10.1080/09540121.2012.712660.
  56. 56.
    Campsmith ML, Rhodes PH, Hall HI, Green TA. Undiagnosed HIV prevalence among adults and adolescents in the United States at the end of 2006. J Acquir Immune Defic Syndr. 2010;53:619–24.PubMedGoogle Scholar
  57. 57.
    Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT. Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years–United States, 2008. MMWR Recomm Rep. 2008;57:1–12.PubMedGoogle Scholar
  58. 58.
    Wilson DP. HIV treatment as prevention: natural experiments highlight limits of antiretroviral treatment as HIV prevention. PLoS Med. 2012;9:e1001231.PubMedCrossRefGoogle Scholar
  59. 59.
    Kharsany AB, Mlotshwa M, Frohlich JA, Zuma NY, Samsunder N, Karim SS, et al. HIV prevalence among high school learners – opportunities for school-based HIV testing programs and sexual reproductive health services. World Health Popul. 2012;13:43–50.PubMedGoogle Scholar
  60. 60.
    Abdool Karim Q, Kharsany AB, Frohlich JA, Werner L, Mlotshwa M, Madlala BT, et al. HIV incidence in young girls in KwaZulu-Natal, South Africa–public health imperative for their inclusion in HIV biomedical intervention trials. AIDS Behav. 2012;16:1870–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Rabkin M, El-Sadr WM. Why reinvent the wheel? Leveraging the lessons of HIV scale-up to confront non-communicable diseases. Glob Public Health. 2011;6:247–56.PubMedCrossRefGoogle Scholar
  62. 62.
    Wood R, Lawn SD. Antiretroviral treatment as prevention: impact of the 'test and treat' strategy on the tuberculosis epidemic. Curr HIV Res. 2011;9:383–92.PubMedCrossRefGoogle Scholar
  63. 63.
    Van Rie A, Page-Shipp L, Scott L, Sanne I, Stevens W. Xpert((R)) MTB/RIF for point-of-care diagnosis of TB in high-HIV burden, resource-limited countries: hype or hope? Expert Rev Mol Diagn. 2010;10:937–46.PubMedCrossRefGoogle Scholar
  64. 64.
    Suthar AB, Lawn SD, del Amo J, Getahun H, Dye C, Sculier D, et al. Antiretroviral therapy for prevention of tuberculosis in adults with HIV: a systematic review and meta-analysis. PLoS Med. 2012;9:e1001270.PubMedCrossRefGoogle Scholar
  65. 65.
    Babiker AG, Emery S, Fatkenheuer G, Gordin FM, Grund B, Lundgren JD, et al. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study. Clin Trials. 2012. doi:10.1177/1740774512440342.
  66. 66.
    Phillips AN, Gazzard B, Gilson R, Easterbrook P, Johnson M, Walsh J, et al. Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naive individuals with high CD4 cell count. AIDS. 2007;21:1717–21.PubMedCrossRefGoogle Scholar
  67. 67.
    El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, Arduino RC, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283–96.PubMedCrossRefGoogle Scholar
  68. 68.
    Phillips AN, Carr A, Neuhaus J, Visnegarwala F, Prineas R, Burman WJ, et al. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther. 2008;13:177–87.PubMedGoogle Scholar
  69. 69.
    Integrated Prevention Services for HIV Infection, Viral Hepatitis, Sexually Transmitted Diseases, and Tuberculosis for Persons Who Use Drugs Illicitly: Summary Guidance from CDC and the U.S. Department of Health and Human Services. MMWR Recomm Rep. 2012;61:1–40.Google Scholar
  70. 70.
    Konate I, Traore L, Ouedraogo A, Sanon A, Diallo R, Ouedraogo JL, et al. Linking HIV prevention and care for community interventions among high-risk women in Burkina Faso–the ARNS 1222 “Yerelon” cohort. J Acquir Immune Defic Syndr. 2011;57 Suppl 1:S50–4.PubMedCrossRefGoogle Scholar
  71. 71.
    Barker PM, Mphatswe W, Rollins N. Antiretroviral drugs in the cupboard are not enough: the impact of health systems’ performance on mother-to-child transmission of HIV. J AIDS. 2011;56:e45.Google Scholar
  72. 72.
    McNairy ML, El-Sadr WM. The HIV care continuum: no partial credit given. AIDS. 2012;26:1735–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Margaret L. McNairy
    • 1
    • 2
  • Myron Cohen
    • 3
  • Wafaa M. El-Sadr
    • 1
  1. 1.ICAP-Columbia UniversityMailman School of Public HealthNew YorkUSA
  2. 2.Weill-Cornell Medical CollegeNew YorkUSA
  3. 3.University of North CarolinaChapel HillUSA

Personalised recommendations