HAART works by dramatically reducing levels of HIV in the blood and tissues. This, in turn, allows the immune system to begin repairing itself,
leading to increased numbers and better functioning of T-cells and other parts of the immune system.
Some researchers have theorized that if many HIV-positive people in a community take HAART, it may reduce their sexual infectiousness at a
population level-thousands of people. Preliminary findings from observational studies with heterosexual people in Southern Africa and injection drug users in
Vancouver suggest that HAART is able to do this in the short-term. However, because of their study design, it is difficult to draw firm conclusions-that is,
to prove a link between cause (taking HAART) and effect (reduced risk of HIV transmission)-in observational studies. Firm conclusions about the impact
of HAART on HIV transmission, at least in heterosexual couples, will be obtained from an international clinical trial called the Strategies in
Timing of AntiRetroviral Treatment (START). This is because part of START will assess HIV transmission in sero-discordant couples.
Most data on estimated risk of HIV transmission comes from heterosexual couples. Using this data, some researchers have theorized that HAART may be
able to reduce the risk of HIV transmission among gay and bisexual men. However, there may be sexual and biological reasons why the risk of HIV transmission is greater among
gay and bisexual men than it is among heterosexual couples.
To try to understand the risk of HIV transmission among men who have sex with men, researchers in Australia undertook a prolonged study. Their analysis is disquieting, suggesting
that the overall risk of HIV transmission among gay and bisexual men has not changed in the era of widely available HAART.
The research team was surprised by its findings, particularly because HAART is widely available and access to health care is subsidized in Australia. Moreover,
the availability of HAART was supposed to, in theory, reduce the risk of HIV transmission at the community level because many men who use HAART should have viral loads less
than 50 or 40 copies/ml in the blood.
The Australian researchers suggested the following possible reasons that may account for their findings:
It is possible that most new HIV infections are inadvertently spread by people who are themselves recently infected (and who are highly infectious) and are unaware of their infection.
It may be possible, they noted, that "HIV transmission by anal intercourse is not as closely related to viral load as it is in vaginal transmission." In other words, it may be easier to
transmit HIV via anal intercourse than vaginal intercourse. This is not surprising because when women are sexually aroused the vagina can produce lubrication, which reduces friction and
damage to the vagina during sex. There is no equivalent response in the anus and insufficient lubrication may predispose the anus to microscopic cuts during sex, providing an entryway
for HIV to get into the body. Furthermore, since the beginning of the AIDS epidemic, unprotected anal sex among men has always been associated with a high risk of HIV transmission
compared to other sex acts.
In Australia and other high-income countries including Canada, rates of sexually transmitted infections (STIs) among gay and bisexual men appear to be greater now than they were
before 1996. STIs, by causing inflammation, sores or lesions on or inside delicate genital tissue, may increase the risk of HIV transmission. A combination of increased high-risk
sex and increased STIs may have overwhelmed any ability of HAART to prevent HIV transmission, at least at the community level among gay and bisexual men in the Australian study.
Not mentioned by the Australian research team is this: Separate groups of scientists in Canada, the European Union and the United States have found that HIV can be detected
in the semen of men who have been taking HAART, who are free of STIs and whose viral load in the blood is less than 50 or 40 copies/ml.
See our previous CATIE News story
for more information about these studies.
Recent reports from Amsterdam, New York and San Francisco suggest that HIV infection has become as common as or even more common among some gay or bisexual men than
it is in the generalized HIV epidemics of sub-Saharan Africa. Taken together, the findings from Australia and other countries suggest that HAART may not greatly reduce the risk
of HIV transmission at the population or community level, at least among gay and bisexual men.
Key points
1. In people who are adherent to HAART and who do not have STIs, HAART will reduce levels of HIV in the blood and sometimes in the semen (and likely other genital fluids).
However, the risk of HIV transmission is not eliminated nor is it negligible. Indeed, sexual transmission of HIV has occurred in multiple cases when viral load in the blood
was less than 50 copies/ml. Use of condoms remains the best way for sexually active adults to prevent the transmission of HIV.
2. HAART has potential for slowing the spread of HIV among gay and bisexual men. However, if a sufficient proportion of gay and bisexual men engage in high-risk
behaviour, HAART's potential for HIV prevention may be very limited. This may be the case, as in the past 10 years researchers have found that rates of STIs,
particularly syphilis, have soared together with reports of high-risk behaviours in several high-income countries. Both of these factors increase the
risk of transmission and likely overwhelm the protective effect of HAART at the level of the community.
Acknowledgement
We thank the many researchers, including experts in infectious diseases, internal medicine, biostatistics and other specialties across Canada, the European Union
and the United States who contributed their time for helpful review, discussion and research assistance.
-Sean R. Hosein
REFERENCES:
1. del Rios C and Curran J. Epidemiology and prevention of acquired immune deficiency syndrome and human immunodeficiency virus infection. In: Mandell GL,
Bennett JE and Dolin R, editors. Principles and Practice of Infectious Diseases. Seventh ed. Philadelphia: Elsevier; 2010. P.1645.
2. Vernazza P, Hirschel B, Bernasconi E, et al. HIV-infizierte Menschen ohne andere STD sind unter wirksamer antiretroviraler Therapie sexuell nicht
infektiös. Schweizerischen Ärztezeitung . 2008;165.
3. Perelson AS, Essunger P, Markowitz M, et al. How long should treatment be given if we had an antiretroviral regimen that completely blocks HIV
replication? In: Program and abstracts of the 11th International Conference on AIDS , 7-12 July 1996, Vancouver, Canada. Abstract ThB 930.
4. Perelson AS, Essunger P, Cao Y, et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature . 1997 May 8;387(6629):188-91.
5. Bonora S, Nicastri E, Calcagno A, et al. Ultrasensitive assessment of residual HIV viraemia in HAART-treated patients with persistently undetectable plasma HIV-RNA:
a cross-sectional evaluation. Journal of Medical Virology . 2009 Mar;81(3):400-5.
6. Kravcik S, Victor G, Houston S, et al. Effect of antiretroviral therapy and viral load on the perceived risk of HIV transmission and the need for safer sexual
practices. Journal of Acquired Immune Deficiency Syndromes . 1998 Oct 1;19(2):124-9.
7. Sheth PM, Kovacs C, Kemal KS, et al. Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS . 2009 Sep 24;23(15):2050-4.
8. Lorello G, la Porte C, Pilon R, et al. Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma. HIV
Medicine . 2009 Oct;10(9):548-54.
9. Pasquier C, Sauné K, Raymond S, et al. Determining seminal plasma human immunodeficiency virus type 1 load in the context of efficient highly active
antiretroviral therapy. Journal of Clinical Microbiology . 2009 Sep;47(9):2883-7.
10. 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 . 2008 Aug 20;22(13):1677-9.
11. Jin F, Prestage GP, Ellard J, et al. How homosexual men believe they became infected with HIV: the role of risk-reduction behaviours. Journal of Acquired
Immune Deficiency Syndromes . 2007 Oct 1;46(2):245-7.
12. Wilson DP, Law MG, Grulich AE, et al. Relation between HIV viral load and infectiousness: a model-based analysis. Lancet . 2008 Jul 26;372(9635):314-20.
13. Wilson DP, Law MG, Gruclich AE, Cooper DA, et al. HIV transmission under highly active antiretroviral therapy. Lancet . 2008 Nov 22;372(9652):1807.
14. Vernazza P, Hirschel B, Bernasconi E, et al. HIV transmission under highly active antiretroviral therapy. Lancet . 2008 Nov 22;372(9652):1806-7.
15. Vernazza PL, Hirschel B. HIV transmission hunting-the chase for low risk events. Antiviral Therapy . 2008;13(5):641-2.
16. Kalichman SC, Di Berto G, Eaton L. Human immunodeficiency virus viral load in blood plasma and semen: review and implications of empirical findings. Sexually
Transmitted Diseases . 2008 Jan;35(1):55-60.
17. 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 Jul 17;23(11):1397-404.
18. Wilson DP. Data are lacking for quantifying HIV transmission risk in the presence of effective antiretroviral therapy. AIDS . 2009 Jul 17;23(11):1431-3.
19. Stürmer M, Doerr HW, Berger A, et al. Is transmission of HIV-1 in non-viraemic serodiscordant couples possible? Antiviral Therapy . 2008;13(5):729-32.
20. Zhang H, Dornadula G, Beumont M, et al. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. New England Journal
of Medicine. 1998 Dec 17;339(25):1803-9.
21. Centers for Disease Control and Prevention. Effect of antiretroviral therapy on risk of sexual transmission of HIV infection and superinfection. September 2009.
Available at: http://www.cdc.gov/hiv/topics/treatment/resources/factsheets/art.htm
[Accessed 28 February 2010].
22. Kalichman S and Eaton L. Strategies for preventing HIV transmission. Journal of the American Medical Association . 2009 Oct 14;302(14):1531.
23. Ghosn J, Chaix ML. Combined antiretroviral therapy is effective on blood plasma HIV-1-RNA: what about semen HIV-1-RNA levels? AIDS . 2010 Jan 16;24(2):309-11.
24. Zuckerman RA, Whittington WL, Celum CL, et al. Higher concentration of HIV RNA in rectal mucosa secretions than in blood and seminal plasma, among men who have sex with men,
independent of antiretroviral therapy. Journal of Infectious Diseases . 2004 Jul 1;190(1):156-61.
25. Crepaz N, Hart TA, Marks G. Highly active antiretroviral therapy and sexual risk behavior: a meta-analytic review. Journal of the American Medical Association .
2004 Jul 14;292(2):224-36.
26. Check Hayden E. Seek, test and treat slows HIV. Nature . 2010 Feb 25;463(7284):1006.
27. El-Sadr WM, Mayer KH, Hodder SL. AIDS in America-forgotten but not gone. New England Journal of Medicine . 2010: in press .
28. Bezemer D, de Wolf F, Boerlijst MC, van Sighem A, et al. A resurgent HIV-1 epidemic among men who have sex with men in the era of potent antiretroviral therapy. AIDS
. 2008 May 31;22(9):1071-7.
29. Bezemer D, van Sighem A, Lukashov VV, et al. Transmission networks of HIV-1 among men having sex with men in the Netherlands. AIDS . 2010 Jan 16;24(2):271-82.
30. 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; in press .
31. Elford J. Changing patterns of sexual behaviour in the era of highly active antiretroviral therapy. Current Opinion in Infectious Diseases . 2006 Feb;19(1):26-32.
32. Haase AT. Targeting early infection to prevent HIV-1 mucosal transmission. Nature . 2010 Mar 11;464(7286):217-23.
33. Virgin HW, Walker BD. Immunology and the elusive AIDS vaccine. Nature . 2010 Mar 11;464(7286):224-31.
###
CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto.
From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca
Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE
