HIV Prevention -- New Strategies Are Under Investigation to Limit HIV's Spread
John G. Bartlett, MD
Robert Grant, MD, of the Gladstone Institute at the University of California, San Francisco, provided a review of novel HIV prevention efforts under investigation. The data for the United States show an estimate of 40,000 new HIV infections per year for 16 consecutive years, and the data for the world show an estimate of 5 million new infections per year. This review addresses strategies that may or may not reduce HIV incidence.
Intensive Counseling. It does not work. The best study is EXPLORE, which compared an intensive intervention of 10 one-hour counseling sessions vs standard, less-intensive counseling in 4295 men who have sex with men (MSM).[1] Results showed a transmission rate of 2.1% and no statistically significant difference between groups; also, any trend in benefit was eliminated after 6 months.
Circumcision. The rationale for circumcision is based on biological (removal of HIV target cells), epidemiologic (low prevalence in circumcised men), and clinical trial data. The ANRS randomized trial[2] showed HIV incidence of 0.85/100 person-years vs 2.1/person years for a relative risk of 0.40. These results are impressive, but the challenges will be safety, cultural acceptance, and scale-up.
Herpes Simplex Virus-2 (HSV-2) Prophylaxis. The indirect supporting evidence includes the observations that:
1. HSV-2 increases the risk for HIV infection 2-fold;
2. HSV-2 infection is associated with an HIV viral load that averages 0.3 log10 copies/mL higher; and
3. HSV-2 infection increases the risk for HIV transmission by 5-fold.[3-5]
There are 2 large trials addressing the potential benefit of HSV-2 suppression to prevent HIV transmission: HPTN 0.39 with 3277 participants (fully enrolled) and Partners in Prevention with 3000 discordant couples (70% enrolled).
Mother-to-child Transmission. The data from multiple studies are summarized in Table 1:
Table 1. Mother-to-Child HIV Transmission Rate, by Strategy
Strategy HIV Transmission Rate
No therapy 20%-40%
Monotherapy 4%-8%
HAART 0%-1.5%
Preexposure Prophylaxis. Several trials are ongoing, as summarized in Table 2:
Table 2. Status of Preexposure Prophylaxis Trials to Prevent HIV Acquisition
Location N Participants Enrollment Follow-up
Ghana 400 High-risk women 2004-2005 2005-2006
US 400 MSM 2005-2007 2007-2009
Thailand 1800 IDU 2005-2007 2007-2008
Botswana 1200 Heterosexual males and females 2007-2008 2008-2009
Andean 1400 MSM 2007-2008 2008-2009
MSM = men who have sex with men; IDU = injection-drug user
All of these studies are blinded and placebo-controlled, and all use tenofovir with or without emtricitabine. Main concerns are increased high-risk behavior, HIV drug resistance, and adverse drug reactions. The first of these trials, the Ghana study, was presented at the 2006 International AIDS Conference in Toronto.[6] There were 8 seroconversions among 400 participants: 6 in placebo recipients and 2 in tenofovir recipients (P = .24). Testing of one seroconverter on tenofovir showed no tenofovir resistance. Analysis of adverse reactions showed none attributed to tenofovir. Interviews with participants showed a reduction in high-risk behavior. The cost of this treatment is determined by the laboratory monitoring and drug costs. For the United States, this ranged from $5000 to $24,000 per person per year.
Serosorting. This refers to selection of sexual/romantic partners by HIV serostatus.
Access to Harm-reduction Messages. The point was made that prevention tools need to be used in order to be effective, and many are. Data from USAID, UNAIDS, and UNICEF Policy Project from June 2004 showed estimates for 2001 and 2003 for access to prevention services