National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, New South Wales, Australia.
Received 3 August, 2010
Accepted 26 August, 2010
Correspondence to David P. Wilson, CFI Building, Corner of West and Boundary Streets, Darlinghurst, Sydney NSW 2010, Australia. Tel: +61 2 9385 0900; fax: +61 2 9385 0920; e-mail: firstname.lastname@example.org
Treatment of HIV-infected people with antiretroviral drugs for the purpose of preventing new infections is gaining support as a public health control strategy. This approach is a shift away from the normal paradigm of using antiretroviral therapy (ART) for the sole objective of keeping HIV-infected people alive, reversing AIDS-defining diseases and improving their health. We are now in a new era wherein the secondary benefits of ART can be considered. The potential population-level impact of ART for prevention has been investigated with mathematical transmission models [1–6]. Models can yield important insights when they are appropriately designed and informed by reliable empirical data. Some of the models used to explore ‘treatment as prevention’ have been criticized due to their structures, assumptions and infeasibility of their applications . However, the new model-based analysis by Johnston et al.  contributes important dimensions to the evaluation of this potential strategy. Their analysis was based on a realistic model with generally appropriate assumptions and they explored the potential population-level impact of reasonable expansions of ART to HIV-infected individuals who are treatment-eligible according to current clinical guidelines. Importantly, they also conservatively assessed that this strategy is likely to be cost-effective.
The most important parameter in any consideration of treatment as prevention is the relative reduction in transmission due to the use of ART. It is important to note that, currently, there are no data available to inform this most crucial parameter for the routes of exposure that are known to be of greatest risk. Studies that have measured associations between viral load and infectiousness or the relative reduction in incidence due to ART have all been conducted among heterosexual couples [9–12]. Currently, there is no reliable measure for the relative reduction in infectiousness due to ART associated with exposure events that are more risky than penile–vaginal sex. The rates of transmission associated with penile–anal sex [13–15] and sharing of injecting equipment or needle-stick injury [16–25] are at least one order of magnitude greater than the risk associated with penile–vaginal sex [26–27]. As ART substantially reduces HIV-RNA in plasma and genital fluids [28–31], it can be expected that infectiousness is decreased due to ART for these riskier exposure routes. However, it is plausible that the degree of reduction in risk will be different to that estimated among heterosexual couples. Emerging data from some cohorts and populations of men who have sex with men (MSM) suggest that HIV incidence has decreased with ART, but not by the extent observed among heterosexuals [31–33]. Similarly, there appears to be an association between incidence and community viral load for people who inject drugs , but the degree of reduction in infectiousness for people on ART is unknown. Consequently, the analysis of Johnston et al. , applied to British Columbia that has a concentrated epidemic with the majority of infections occurring among MSM and people who inject drugs, should be reviewed cautiously.
It is likely to be difficult to empirically estimate the relative reduction in infectiousness due to ART associated with penile–anal or injection-related transmission. These riskier transmission routes are important for the spread of HIV worldwide. Therefore, any public health strategies that may reduce these transmission risks should be considered. However, in the absence of empirical data on the effect of ART on infectiousness, any model-based evaluation should also be accompanied by an extensive uncertainty and sensitivity analysis, including assumptions that transmission rates do not decrease for transmission routes of injecting or male homosexual contact to the same extent as for heterosexual contact.
1. 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.
2. Lima VD, Johnston K, Hogg RS, Levy AR, Harrigan PR, Anema A, et al
. Expanded access to highly active antiretroviral therapy: a potentially powerful strategy to curb the growth of the HIV epidemic. J Infect Dis 2008; 198:59–67.
3. Velasco-Hernandez JX, Gershengorn HB, Blower SM. Could widespread use of combination antiretroviral therapy eradicate HIV epidemics? Lancet Infect Dis 2002; 2:487–493.
4. Baggaley RF, Garnett GP, Ferguson NM. Modelling the impact of antiretroviral use in resource-poor settings. PLoS Med 2006; 3:e124.
5. Salomon JA, Hogan DR. Evaluating the impact of antiretroviral therapy on HIV transmission. AIDS 2008; 22(Suppl 1):S149–S159.
6. Wilson DP, Hoare A, Regan DG, Law MG. Importance of promoting HIV testing for preventing secondary transmissions: modelling the Australian HIV epidemic among men who have sex with men. Sex Health 2009; 6:19–33.
7. Wilson DP. Universal voluntary HIV testing and immediate antiretroviral therapy. Lancet 2009; 373:1077–1078, author reply 1080–1081.
8. Johnston KM, Levy AR, Lima VD, Hogg RS, Tyndall MW, Gustafson P, et al
. Expanding access to HAART: a cost-effective approach for treating and preventing HIV. AIDS 2010; 24:1929–1935.
9. Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li CJ, Wabwire-Mangen F, et al
. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 2000; 342:921–929.
10. Donnell D, Baeten JM, Kiarie J, Thomas KK, Stevens W, Cohen CR, et al
. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 2010; 375:2092–2098.
11. 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 2009; 23:1397–1404.
12. Del Romero J, Castilla J, Hernando V, Rodriguez C, Garcia S. Combined antiretroviral treatment and heterosexual transmission of HIV-1: cross sectional and prospective cohort study. BMJ 2010; 340:c2205.
13. Jin F, Jansson J, Law M, Prestage GP, Zablotska I, Imrie JC, et al
. Per-contact probability of HIV transmission in homosexual men in Sydney in the era of HAART. AIDS 2010; 24:907–913.
14. 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; 39:1048–1063.
15. Vittinghoff E, Douglas J, Judson F, McKirnan D, MacQueen K, Buchbinder SP. Per-contact risk of human immunodeficiency virus transmission between male sexual partners. Am J Epidemiol 1999; 150:306–311.
16. Henderson DK, Fahey BJ, Willy M, Schmitt JM, Carey K, Koziol DE, et al
. Risk for occupational transmission of human immunodeficiency virus type 1 (HIV-1) associated with clinical exposures. A prospective evaluation. Ann Intern Med 1990; 113:740–746.
17. Cavalcante NJ, Abreu ES, Fernandes ME, Richtmann R, Piovesana MN, Yamada FT, et al
. Risk of healthcare professionals acquiring HIV infection in Latin America. AIDS Care 1991; 3:311–316.
18. Gerberding JL. Incidence and prevalence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and cytomegalovirus among healthcare personnel at risk for blood exposure: final report from a longitudinal study. J Infect Dis 1994; 170:1410–1417.
19. Ippolito G, Puro V, De Carli G. The risk of occupational human immunodeficiency virus infection in healthcare workers. Italian Multicenter Study. The Italian Study Group on Occupational Risk of HIV infection. Arch Intern Med 1993; 153:1451–1458.
20. Nelsing S, Nielsen TL, Nielsen JO. Occupational exposure to human immunodeficiency virus among healthcare workers in a Danish hospital. J Infect Dis 1994; 169:478.
21. Tokars JI, Marcus R, Culver DH, Schable CA, McKibben PS, Bandea CI, et al
. Surveillance of HIV infection and zidovudine use among healthcare workers after occupational exposure to HIV-infected blood. The CDC Cooperative Needlestick Surveillance Group. Ann Intern Med 1993; 118:913–919.
22. Patz JA, Jodrey D. Occupational health in surgery: risks extend beyond the operating room. Aust NZ J Surg 1995; 65:627–629.
23. Kaplan EH, O'Keefe E. Let the needles do the talking! Evaluating the New Haven needle exchange. Interfaces 1993; 23:7–26.
24. Hudgens MG, Longini IM Jr, Vanichseni S, Hu DJ, Kitayaporn D, Mock PA, et al
. Subtype-specific transmission probabilities for human immunodeficiency virus type 1 among injecting drug users in Bangkok, Thailand. Am J Epidemiol 2002; 155:159–168.
25. Baggaley RF, Boily MC, White RG, Alary M. Risk of HIV-1 transmission for parenteral exposure and blood transfusion: a systematic review and meta-analysis. AIDS 2006; 20:805–812.
26. Powers KA, Poole C, Pettifor AE, Cohen MS. Rethinking the heterosexual infectivity of HIV-1: a systematic review and meta-analysis. Lancet Infect Dis 2008; 8:553–563.
27. Boily MC, Baggaley RF, Wang L, Masse B, White RG, Hayes RJ, et al
. Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies. Lancet Infect Dis 2009; 9:118–129.
28. Vernazza PL, Gilliam BL, Dyer J, Fiscus SA, Eron JJ, Frank AC, et al
. Quantification of HIV in semen: correlation with antiviral treatment and immune status. AIDS 1997; 11:987–993.
29. Vernazza PL, Troiani L, Flepp MJ, Cone RW, Schock J, Roth F, et al
. Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. The Swiss HIV Cohort Study. AIDS 2000; 14:117–121.
30. Zhang H, Dornadula G, Beumont M, Livornese L Jr, Van Uitert B, Henning K, et al
. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. N Engl J Med 1998; 339:1803–1809.
31. Porco TC, Martin JN, Page-Shafer KA, Cheng A, Charlebois E, Grant RM, et al
. Decline in HIV infectivity following the introduction of highly active antiretroviral therapy. AIDS 2004; 18:81–88.
32. 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.
33. Fisher M, Pao D, Brown AE, Sudarshi D, Gill ON, Cane P, et al
. Determinants of HIV-1 transmission in men who have sex with men: a combined clinical, epidemiological and phylogenetic approach. AIDS 2010; 24:1739–1747.
34. Wood E, Kerr T, Marshall BD, Li K, Zhang R, Hogg RS, 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.