Biomedical methods for HIV prevention: new setbacks.

In terms of prevention, I will focus on 4 main issues. First, there is the problem of identifying those recently infected with HIV. Annual HIV transmission rates in the United States are 3.5-fold higher among persons with undiagnosed infection as among those who know they are infected.1 Groups classically identified as low risk for HIV infection, such as married heterosexual men with children, are at particularly high risk for late testing.2 But there is no clear plan as to the best, most cost-effective means for accelerating early identification of new HIV infections, be it opt-out testing, concentrating efforts on those most at risk for transmission (MART), or some combination of the two.3 Of additional concern was the persistent failure of physicians to recognize patients with primary HIV infection (PHI). In upwards of 90% of persons with PHI, a symptomatic seroconversion illness develops.4 Although symptoms of PHI are nonspecific, it is at this initial stage in the disease course that there is a chance to make a diagnosis of HIV infection before the development of advanced disease. Diagnosis during PHI offers an opportunity to intervene to prevent HIV transmission at a time of markedly heightened infectivity.4 Unfortunately, diagnosing PHI has been problematic. In a large study of patients with recent HIV infection seen in an HIV clinic in the United Kingdom, the diagnosis of PHI was missed about half the time.4 In the period between 2003 and 2005, recent infection (defined as a previous negative HIV antibody test within 18 months, an evolving Western blot analysis result, or identification via a serological testing algorithm) was diagnosed in 108 persons.4 Of these, 93 (86%) were men who have sex with men (MSM) and 76 (70%) reported seroconversion symptoms, including fever (55%), rash (37%), pharyngitis (33%), diarrhea (28%), and lymphadenopathy (21%). Of these 76 with symptoms, 40 (53%) presented to a health care provider during this symptomatic period, and in only 21 (52%) of these patients was PHI diagnosed.4 Of the 19 "missed opportunities," 16 were MSM, 1 was a bisexual man, and 2 were heterosexual women. All were white. Second, there is the issue of how to prevent HIV transmission once the infection is recognized. There has been good news and bad news. Encouraging data derived from a 3-year study of the effect of antiretroviral therapy on sexual HIV transmission risk in Africa. Between May 2003 and May 2007, 928 antiretroviral-naive persons were enrolled in a home-based AIDS care program in Uganda.5 HIV seroconversion rates were determined among cohabitating HIV-discordant couples following antiretroviral therapy initiation. Although the proportion of sexually active participants reporting risky sex declined somewhat, from 22% at baseline to 14% at 36 months, the median HIV RNA level of those reporting risky sex fell dramatically, from 122,500 copies/mL to undetectable over the same period.5 This was accompanied by a 92% reduction in estimated risk of HIV transmission, from 45.7 to 4.2 per 1000 person-years. This does not mean that lesser forms of antiretroviral therapy, such as a single drug used to attempt preexposure prophylaxis, will be effective. Daily and intermittent preexposure prophylaxis regimens of increasing antiviral activity were recently assessed in a macaque model closely mimicking human transmission.6 Using emtricitabine alone or in combination with tenofovir at concentrations typically