Current HIV/AIDS Reports

, Volume 8, Issue 2, pp 85–93 | Cite as

Antiretroviral Therapy: A Key Component of a Comprehensive HIV Prevention Strategy

  • Mark W. Hull
  • Julio MontanerEmail author


Transmission of HIV is critically dependent on the level of HIV viral load within blood and genital secretions. Antiretroviral therapy results in sustained reductions in viral load to undetectable levels. Thus, antiretroviral therapy has long been postulated as a potential means to curb HIV transmission. Observational data have now confirmed that antiretroviral therapy is associated with a decrease in transmission among heterosexual serodiscordant couples, injection-drug users, and in population-based studies. Mathematical models suggest that further expansion of antiretroviral coverage within current guidelines can play a major role in controlling the spread of HIV. Concerns regarding the potential for transmission during acute HIV infection, behavioral disinhibition, and resistance to overcome the impact of treatment on prevention have not materialized to date. The Joint United Nations AIDS (UNAIDS) program has called for the inclusion of antiretroviral treatment as a key pillar in the global strategy to control the spread of HIV infection.


HIV transmission Serodiscordant couples Antiretroviral therapy Mathematical models Treatment as prevention 



M. W. Hull: consultant to Janssen-Ortho and Sepracor; J. Montaner: consultant to Merck.


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

  1. 1.
    Kaposi’s sarcoma and Pneumocystis pneumonia among homosexual men--New York City and California. MMWR 1981;30(25):305–8, Jul 3.Google Scholar
  2. 2.
    UNAIDS. Report on the global AIDS epidemic. 2010.Google Scholar
  3. 3.
    Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. NEngl J Med. 1997;337(11):725–33.CrossRefGoogle Scholar
  4. 4.
    Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, 1995–2005. Ann Intern Med. 2007;146(2):87–95.PubMedGoogle Scholar
  5. 5.
    Hall HI, Song R, Rhodes P, et al. Estimation of HIV incidence in the United States. JAMA. 2008;300(5):520–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007;369(9562):643–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet. 2007;369(9562):657–66.PubMedCrossRefGoogle Scholar
  8. 8.
    ••Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010;329(5996):1168–74, New York, NY Sep 3. First clinical trial documenting that a vaginal preparation of tenofovir was associated with decreased transmission of HIV.Google Scholar
  9. 9.
    Buchbinder SP, Mehrotra DV, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008;372(9653):1881–93.PubMedCrossRefGoogle Scholar
  10. 10.
    Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361(23):2209–20.PubMedCrossRefGoogle Scholar
  11. 11.
    Townsend CL, Cortina-Borja M, Peckham CS, de Ruiter A, Lyall H, Tookey PA. Low rates of mother-to-child transmission of HIV following effective pregnancy interventions in the United Kingdom and Ireland, 2000–2006. AIDS (London, England). 2008;22(8):973–81.CrossRefGoogle Scholar
  12. 12.
    Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000;342(13):921–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Tovanabutra S, Robison V, Wongtrakul J, et al. Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand. JAIDS (1999). 2002;29(3):275–83.Google Scholar
  14. 14.
    Zhang H, Dornadula G, Beumont M, et al. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. N Engl J Med. 1998;339(25):1803–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Cohen MS, Gay C, Kashuba AD, Blower S, Paxton L. Narrative review: antiretroviral therapy to prevent the sexual transmission of HIV-1. Ann Intern Med. 2007;146(8):591–601.PubMedGoogle Scholar
  16. 16.
    Graham SM, Holte SE, Peshu NM, et al. Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding. AIDS (London, England). 2007;21(4):501–7.CrossRefGoogle Scholar
  17. 17.
    Chan DJ, Ray JE, McNally L, Batterham M, Smith DE. Correlation between HIV-1 RNA load in blood and seminal plasma depending on antiretroviral treatment status, regimen and penetration of semen by antiretroviral drugs. Curr HIV Res. 2008;6(5):477–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Ghosn J, Viard JP, Katlama C, et al. Evidence of genotypic resistance diversity of archived and circulating viral strains in blood and semen of pre-treated HIV-infected men. AIDS (London, England). 2004;18(3):447–57.CrossRefGoogle Scholar
  19. 19.
    Liuzzi G, Chirianni A, Zaccarelli M, et al. Differences between semen and plasma of nucleoside reverse transcriptase resistance mutations in HIV-infected patients, using a rapid assay. In vivo (Athens, Greece). 2004;18(4):509–12.Google Scholar
  20. 20.
    Marcelin AG, Tubiana R, Lambert-Niclot S, et al. Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma. AIDS (London, England). 2008;22(13):1677–9.CrossRefGoogle Scholar
  21. 21.
    Lorello G, la Porte C, Pilon R, Zhang G, Karnauchow T, MacPherson P. Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma. HIV Med. 2009;10(9):548–54.PubMedCrossRefGoogle Scholar
  22. 22.
    •Sheth PM, Kovacs C, Kemal KS, et al. Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS (London, England) 2009;23(15):2050–4, Sep 24. Cohort study of men initiating antiretroviral therapy documenting intermittent detectable viral loads in seminal fluid despite suppression of plasma viral load.Google Scholar
  23. 23.
    Kalichman SC, Di Berto G, Eaton L. Human immunodeficiency virus viral load in blood plasma and semen: review and implications of empirical findings. Sex Transm Dis. 2008;35(1):55–60.PubMedCrossRefGoogle Scholar
  24. 24.
    Castilla J, Del Romero J, Hernando V, Marincovich B, Garcia S, Rodriguez C. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. JAIDS (1999). 2005;40(1):96–101.CrossRefGoogle Scholar
  25. 25.
    Sullivan PS, Kayetinkore K, Chomba E et al. Reduction of HIV Transmission Risk and High Risk Sex while Prescribed ART: Results from Discordant Couples in Rwanda and Zambia. [abstract52bLB]. Presented at the 16th Conference on Retroviruses and Opportunistic Infections. Montreal, Canada; February 8–11, 2009.Google Scholar
  26. 26.
    Celum C, Wald A, Lingappa JR, et al. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med. 2010;362(5):427–39.PubMedCrossRefGoogle Scholar
  27. 27.
    Lingappa JR, Baeten JM, Wald A, et al. Daily acyclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial. Lancet. 2010;375(9717):824–33.PubMedCrossRefGoogle Scholar
  28. 28.
    ••Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 2010;375(9731):2092–8, Jun 12. Cohort study nested with the HSV suppression trial which demonstrates that provision of HAART in the setting of heterosexual discordant couples was associated with reduced sexual transmission.Google Scholar
  29. 29.
    •Attia S, Egger M, Muller M, Zwahlen M, Low N. Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. AIDS (London, England) 2009;23(11):1397–404, Jul 17. Important meta-analysis of heterosexual transmission of HIV.Google Scholar
  30. 30.
    Wang L, Ge Z, Luo J, et al. HIV Transmission Risk Among Serodiscordant Couples: A Retrospective Study of Former Plasma Donors in Henan, China. JAIDS (1999). 2010;55(2):232–8.CrossRefGoogle Scholar
  31. 31.
    Fox J, Fidler S. Sexual transmission of HIV-1. Antiviral Res;85(1):276–85, Jan.Google Scholar
  32. 32.
    Baggaley RF, White RG, Boily MC. HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention. Int J Epidemiol. 2010;39(4):1048–63.PubMedCrossRefGoogle Scholar
  33. 33.
    •Jin F, Jansson J, Law M, et al. Per-contact probability of HIV transmission in homosexual men in Sydney in the era of HAART. AIDS 2010 (London, England) 24(6):907–13, Mar 27. This study assessed per-contact transmission of HIV among MSM. Transmission rates remain similar to other pre-HAART estimates, despite assumed acceptable uptake of HAART in the community.Google Scholar
  34. 34.
    Falster K, Gelgor L, Shaik A, et al. Trends in antiretroviral treatment use and treatment response in three Australian states in the first decade of combination antiretroviral treatment. Sex Health. 2008;5(2):141–54.PubMedCrossRefGoogle Scholar
  35. 35.
    Wilson DP, Jin F, Jansson J, Zablotska I, Grulich AE. Infectiousness of HIV-infected men who have sex with men in the era of highly active antiretroviral therapy. AIDS. 2010;24(15):2420–1.PubMedCrossRefGoogle Scholar
  36. 36.
    Baggaley RF, Fraser C. Modelling sexual transmission of HIV: testing the assumptions, validating the predictions. Curr Opin HIV AIDS. 2010;5(4):269–76.PubMedCrossRefGoogle Scholar
  37. 37.
    Blower SM, Gershengorn HB, Grant RM. A tale of two futures: HIV and antiretroviral therapy in San Francisco. Science (New York, NY). 2000;287(5453):650–4.CrossRefGoogle Scholar
  38. 38.
    Velasco-Hernandez JX, Gershengorn HB, Blower SM. Could widespread use of combination antiretroviral therapy eradicate HIV epidemics? Lancet Infect Dis. 2002;2(8):487–93.PubMedCrossRefGoogle Scholar
  39. 39.
    Cohen MS, Gay CL. Treatment to prevent transmission of HIV-1. Clin Infect Dis. 2010;50 Suppl 3:S85–95.PubMedCrossRefGoogle Scholar
  40. 40.
    •Lima VD, Johnston K, Hogg RS, et al. Expanded access to highly active antiretroviral therapy: a potentially powerful strategy to curb the growth of the HIV epidemic. Journal of Infectious Diseases 2008;198(1):59–67, Jul 1. Mathematical model demonstrating potential reduction in HIV diagnoses linked to expanding HAART coverage within 2006 guideline parameters.Google Scholar
  41. 41.
    Lima VD, Hogg RS, Montaner JS. Expanding HAART treatment to all currently eligible individuals under the 2008 IAS-USA Guidelines in British Columbia, Canada. PLoS ONE. 2010;5(6):e10991.PubMedCrossRefGoogle Scholar
  42. 42.
    ••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 Jan 3;373(9657):48–57. Important mathematical model set in South Africa examining a test and treat approach to eliminating the HIV epidemic within Africa.Google Scholar
  43. 43.
    Dodd PJ, Garnett GP, Hallett TB. Examining the promise of HIV elimination by ‘test and treat’ in hyperendemic settings. AIDS (London, England). 2010;24(5):729–35.CrossRefGoogle Scholar
  44. 44.
    •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(4):392–400, Aug 15. Mathematical model of test and treat assumptions within Washington, DC. While expansion of HAART was associated with decreased transmission, it was unlikely to halt the epidemic.Google Scholar
  45. 45.
    •Wood E, Kerr T, Marshall BD, et al. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study. BMJ 2009;338:b1649. Assessment of effects of community viral load and time to HIV seroconversion. After community viral load was reduced, there was no longer a statistically significant association with HIV incidence.Google Scholar
  46. 46.
    ••Das M, Chu PL, Santos GM, et al. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PloS One 2010;5(6):e11068. Assessment of community viral load and new HIV diagnoses in San Francisco. HAART expansion and reduction in viral load was associated with decrease in new HIV diagnoses.Google Scholar
  47. 47.
    ••Montaner JS, Lima VD, Barrios R, 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(9740):532–9, Aug 14. Population-based Canadian study documenting that expansion of HAART was associated with decreases in community viral load and decreases in new HIV diagnoses.Google Scholar
  48. 48.
    Morrison CS, Demers K, Kwok C, et al. Plasma and cervical viral loads among Ugandan and Zimbabwean women during acute and early HIV-1 infection. AIDS (London, England). 2010;24(4):573–82.CrossRefGoogle Scholar
  49. 49.
    Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis. 2005;191(9):1403–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Hollingsworth TD, Anderson RM, Fraser C. HIV-1 transmission, by stage of infection. J Infect Dis. 2008;198(5):687–93.PubMedCrossRefGoogle Scholar
  51. 51.
    Prabhu VS, Hutchinson AB, Farnham PG, Sansom SL. Sexually acquired HIV infections in the United States due to acute-phase HIV transmission: an update. AIDS (London, England). 2009;23(13):1792–4.CrossRefGoogle Scholar
  52. 52.
    Marshall BD, Milloy MJ, Kerr T, Zhang R, Montaner JS, Wood E. No evidence of increased sexual risk behaviour after initiating antiretroviral therapy among people who inject drugs. AIDS (London, England). 2010;24(14):2271–8.CrossRefGoogle Scholar
  53. 53.
    Venkatesh KK, de Bruyn G, Lurie MN, et al. Decreased sexual risk behavior in the era of HAART among HIV-infected urban and rural South Africans attending primary care clinics. AIDS (London, England). 2010;24(17):2687–96.CrossRefGoogle Scholar
  54. 54.
    Smith RJ, Okano JT, Kahn JS, Bodine EN, Blower S. Evolutionary dynamics of complex networks of HIV drug-resistant strains: the case of San Francisco. Science (New York, NY). 2010;327(5966):697–701.CrossRefGoogle Scholar
  55. 55.
    Gill VS, Lima VD, Zhang W, et al. Improved virological outcomes in British Columbia concomitant with decreasing incidence of HIV type 1 drug resistance detection. Clin Infect Dis. 2010;50(1):98–105.PubMedCrossRefGoogle Scholar
  56. 56.
    Johnston KM, Levy AR, Lima VD, et al. Expanding access to HAART: a cost-effective approach for treating and preventing HIV. AIDS (London, England). 2010;24(12):1929–35.CrossRefGoogle Scholar
  57. 57.
    Coates TJ, Richter L, Caceres C. Behavioural strategies to reduce HIV transmission: how to make them work better. Lancet. 2008;372(9639):669–84.PubMedCrossRefGoogle Scholar
  58. 58.
    Reynolds SJ, Quinn TC. Setting the stage: current state of affairs and major challenges. Clin Infect Dis. 2010;50 Suppl 3:S71–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Fang CT, Hsu HM, Twu SJ, et al. Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan. J Infect Dis. 2004;190(5):879–85.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.From the British Columbia-Centre for Excellence in HIV/AIDS, at St Paul’s Hospital, Providence Health Care and Division of AIDS, Department of MedicineUniversity of British ColumbiaVancouverCanada
  2. 2.Professor and Head, Division of AIDS, Department of MedicineUniversity of British ColumbiaVancouverCanada

Personalised recommendations