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SPECIAL ARTICLES: Review of AIDS Literature

CAN ANTIRETROVIRAL THERAPY BE USED TO PREVENT SEXUAL TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1?

Infectious Diseases in Clinical Practice: March-April 2002 - Volume 11 - Issue 3 - p 178-179
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CAN ANTIRETROVIRAL THERAPY BE USED TO PREVENT SEXUAL TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1?

[Hosseinipour M, et al. CID 2002;34:1391]:

The authors review the issues regarding reduction in viral load and its impact on sexual transmission of HIV infection with the following major points:

  • Prevention of Mother-Child Transmission: The association between viral load and risk of transmission is clearly established, but this mechanism of transmission and sexual transmission are not “analogous biologic events.” Furthermore, transmission has occurred even when HIV RNA cannot be detected in the mother at the time of delivery, making it a good but imperfect correlation [NEJM 1998;339:1409].
  • Prevention of Sexual Transmission: It is clear that the viral load in the source patient is a critical determinant in the probability of transmission according to studies of discordant couples [NEJM 2000;342:921]. Most but not all studies show a direct correlation between HIV RNA concentrations in blood and genital fluid [AIDS 2000;14:117;AIDS 2000;14:415]. AZT and 3TC are concentrated in seminal fluid, but PIs appear to penetrate poorly [Antimicrob Agents Chemother 1999;43:1817]. There has been one observational study of 436 couples in which some HIV-infected men received AZT monotherapy; this showed a 50% reduction in risk of transmission, but the same study showed an 80% reduction with condom use [Arch Intern Med 1994;154:1971].
  • Resistance: An obvious concern is transmission of resistant HIV and an estimate that about 15.6% of new HIV infections in the year 2005 will involve strains resistant to antiretroviral agents [Nat Med 2001;7:1016]. But this frequency is highly dependent on adherence. It was noted that in Switzerland, where compliance with drug administration is good, the frequency of transmission of resistant strains has been decreasing since 1996.
  • Risk Taking: There is great concern that high risk behavior is increasing as indicated by increased rates of STDs in selected patients with HIV infection [Am J Public Health 2002;92:388]. Mathematical modeling suggests that a 10% increase in sexual risk taking will offset the protective effect of antiretroviral therapy [Science 2000;287:650;Nat Med 2001;7:1016;AIDS 2001;15:1287]. An additional concern is that the increased frequency of STDs will also promote HIV transmission independent of viral load.
  • Tenofovir: The authors note that this drug has shown particular promise in prevention of transmission of the simian immunodeficiency virus infection in macaques [J Virol 2000;74:9771], but the experience in patients is limited to a small study of PEP with AZT [NEJM 1997;337:1485].
  • Post Exposure Prophylaxis: The San Francisco PEP study included 400 persons who presented within 72 hours of sexual exposure [J Infect Dis 2001;183:707]. Treatment was initiated at an average of 33 hours post exposure, and 78% completed the four-week course. There were no seroconversions. A study from Brazil [CROI February, 2001, Seattle, Abstract 225] was similar except subjects were provided the initial four days of PEP to be taken immediately after perceived exposure. Subsequent evaluation indicated appropriate use in about 90% of cases. The data are too preliminary for any recommendation.
  • Conclusions: Antiretroviral therapy is considered “a potential tool” to reduce HIV transmission, but this needs to be accompanied by patient education/counseling and emphasis on the importance of adherence.
© 2002 Lippincott Williams & Wilkins, Inc.