Topical microbicides

An exciting area of prevention research involves topical preparations containing virucidal agents. Several studies are ongoing. One multicenter international Phase 3 study utilized cellulose sulfate in a placebo-controlled, double-blinded protocol.11 Cellulose sulfate, which is safe and effective in preventing pregnancy, also interferes with HIV’s ability to enter susceptible human cells. An interim analysis of 1,333 participants, however, showed that the agent was not effective in preventing HIV infection, and the study was terminated early.12

Tenofovir, a nucleotide analog that has been approved to treat HIV infection, is also being studied as a topical microbicide. One animal study yielded encouraging results. Using a gel impregnated with tenofovir, researchers were able to protect six of nine rhesus macaques from rectal challenge with simian immunodeficiency virus, which is frequently used as a surrogate animal model for HIV.13 In contrast, four of four untreated controls and three of four macaques who received placebo gel seroconverted after the same exposure. Further investigation with tenofovir gel is likely.

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Averting infection following exposure

Antiretroviral post-exposure prophylaxis (PEP) after occupational HIV exposure has been shown to reduce the rate of infection by 79%.14 PEP is widely used after sexual exposure to HIV, although no studies have been done to prove its efficacy.

Could pre-exposure prophylaxis (sometimes called “PrEP”) work? A multicenter study using single-dose tenofovir is now under way.

Conclusion

Until we have an effective vaccine, we will continue to counsel our patients to rely on behavioral modifications to avoid HIV infection. All clinicians are aware of their limitations in helping patients make significant lifestyle changes. It is imperative to take the time to ask what our patients are doing sexually and if they are using drugs in a way that exposes them to the blood of others. Screening for and possible treatment of HSV-2 infection is worth considering, although screening of asymptomatic patients is not currently the standard of care.

Acute or primary HIV infection deserves a place on the differential list when patients present with flulike illnesses. If HIV is determined to be the cause, the patient and the public are well-served by the clinician who makes the diagnosis.

Finally, do not overlook the ability to diagnose those with unknown chronic HIV infection. Patients’ awareness of their HIV status is a powerful motivator to change behavior. The CDC recommends that all patients between the ages of 13 and 64 be tested routinely for HIV infection in all care settings, including primary care, emergency departments, and urgent-care clinics. The CDC recommends an “opt-out” model in which patients are informed that they will be tested unless they decline. “Rapid tests,” which give results in 20-40 minutes, are available for use with saliva or blood. These have sensitivities approaching 100% and need confirmatory testing with Western blot assays. Patients are more likely to get their results because they are available on the same day.

Dr. Armington is an internist in New York City who specializes in caring for patients with HIV and AIDS.

References

  1. Gorbach P, Javanbakht M, Drumright I. Transmission behavior over time in a cohort of newly HIV-infected MSM. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Abstract 968.
  2. Nieuwkerk PT, Oort FJ. Self-reported adherence to antiretroviral therapy for HIV-1 infection and virologic treatment response: a meta-analysis. J Acquir Immun Defic Syndr. 2005;39:445-448.
  3. Magder LS, Mofenson L, Paul ME, et al. Risk factors for in utero and intrapartum transmission of HIV. JAIDS. 2005;38:87-95.
  4. Bezemer D, de Wolf F, Boerlijst M, et al. Despite HAART, HIV-1 is once again spreading epidemically among men having sex with men in theNetherlands. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Abstract 151.
  5. Delany S, Mayaud P, Clayton T, et al. Impact of HSV-2 suppressive therapy on genital and plasma HIV-1 RNA in HIV-1 and HSV-2 seropositive women not taking ART: a randomized, placebo-controlled trial in Johannesburg, South Africa. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Abstract 154LB.
  6. Dunne E, Whitehead S, Sternberg M, et al. The effect of suppressive acyclovir therapy on HIV cervicovaginal shedding in HIV- and HSV-2-infected women, Chiang Rai, Thailand. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Abstract 30.
  7. Whitehead S, Bollen L, Leelawiwat W, et al. Maternal HSV-2 cervicovaginal shedding increases the risk of intrapartum HIV-1 transmission. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Abstract 75.
  8. Gray R, Kigozi G, Serwadda D, et al. Randomized trial of male circumcision for HIV prevention in Rakai, Uganda. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Poster session 155aLB.
  9. Wawer M, Gray R, Kigozi G, et al. The effects of male circumcision on genital ulcer disease and urethral symptoms, and on HIV acquisition: an RCT in Rakaia, Uganda. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Poster session 155bLB.
  10. Begley E, Jafa K, Voetsch A, et al. Willingness of men who have sex with men in the US to be circumcised as adults to reduce risk of HIV infection. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Poster session 983.
  11. Nachega J, Hislop M, Dowdy D. Efavirenz- vs nevirapine-based ART regimens: adherence and virologic outcomes. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Poster session 33.
  12. Doncel G, van Damme L. Update on the CONRAD cellulose sulfate trial, preclinical evaluation of cellulose sulfate. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Poster session 106LB.
  13. Cranage M, Sharpe S, Cope A, et al. Pre-exposure prophylaxis in macaques against rectal SIV challenge by mucosally applied PMPA: potential for complementation of microbicide and vaccination strategies. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007; Los Angeles, Calif. Poster session 29.
  14. Gerberding JL. Clinical practice. Occupational exposure to HIV in health care settings. N Engl J Med. 2003;348:826-833.

From the December 14, 2007 Issue of Clinical Advisor

Topics:

HIV/AIDS