HIV This Week

Hawes SE, Sow PS, Stern JE, Critchlow CW, Gottlieb GS, Kiviat. Lower levels of HIV-2 than HIV-1 in the female genital tract: correlates and longitudinal assessment of viral shedding. AIDS. 2008;22(18):2517-25.

The differing magnitude of the HIV-1 and HIV-2 epidemics is likely a consequence of differing transmission rates between the two viruses. Similar to other sexually transmitted pathogens, risk of HIV-1 and HIV-2 transmission is likely associated with the presence and amount of HIV in the genital tract. Thus, understanding patterns of, and risk factors for HIV genital tract shedding is critical to effective control of HIV transmission. Hawes and colleagues evaluated HIV DNA and RNA detection in cervicovaginal specimens among 168 HIV-1 and 50 HIV-2-infected women in Senegal, West Africa. In a subset of 31 women (20 with HIV-1, 11 with HIV-2), they conducted a prospective study in which cervicovaginal specimens were taken at 3-day intervals over a 6-week period. The authors found significantly lower rates and levels of HIV-2 RNA (58% shedding; 13% with >1000 copies/ml) in the female genital tract than HIV-1 RNA (78% shedding; 40% with >1000 copies/ml) (P = 0.005 and 0.005, respectively), and shedding correlated with plasma viral load irrespective of virus type (odds ratio = 1.9, 95% confidence interval = 1.3-2.8 for each log10 increase in HIV viral RNA). Plasma viral load, not HIV type, was the strongest predictor of genital viral load. Over 80% of closely monitored women, regardless of HIV type, had at least intermittent HIV RNA detection during every 3-day sampling over a 6-week time period. These data help in explaining the different transmission rates between HIV-1 and HIV-2 and may provide new insights regarding prevention.

Editors’ note: This first prospective study of closely followed women reveals that HIV shedding in untreated women is common. The lower detection rates and levels of HIV-2 RNA compared to HIV-1 RNA found in the female genital tract in the comparative part of this study may explain in part why HIV-2 transmission is limited primarily to West Africa whereas HIV-1 spread is pandemic.

Five percent of 145 HIV-1-infected men enrolled in an assisted reproductive technology programme harboured detectable HIV-1 RNA in semen, although they had no other sexually transmitted disease and their blood viral load was undetectable for at least 6 months under antiretroviral treatment. This result justifies measuring HIV-1 RNA in semen before the assisted reproductive technology process and suggests that a residual risk of transmission has to be mentioned to the patients who would like to have unprotected sexual intercourse.

Editors’ note : The authors cite the Swiss Commission Fédérale’s report that a seropositive person who has no other sexually transmitted disease, is under antiretroviral treatment, and has had an undetectable plasma viral load for at least 6 months does not sexually transmit HIV. The results of this study demonstrate a viral load disconnect between the plasma and semen compartments in some men. Although antiretroviral therapy is the preferred method, when accessible, to avoid HIV transmission in serodiscordant couples desiring to have a child, the authors underscore the importance of explaining that the risk is certainly low but is not null.

The aim of the study was to estimate the impact of small changes in plasma levels of HIV-1 RNA on the risk of heterosexual transmission or disease progression to an AIDS-defining event or death. Modjarrad and colleagues systematically reviewed the published literature for studies that evaluated small viral load changes among antiretroviral-therapy-naive, adult populations. They modelled relative risk estimates for viral transmission and disease progression according to 0.3, 0.5, and 1.0 log10 increments of HIV load. They calculated that the likelihood of transmitting HIV by heterosexual contact increased, on average, by 20% and that the annual risk of progression to an AIDS-defining illness or related death increased by 25% with every 0.3 log10 increment in HIV RNA. A 0.5 log10 increment in HIV RNA was associated with 40% greater risk of heterosexual transmission and 44% increased risk of progression to AIDS or death. A 1.0 log10 increment in HIV RNA was associated with 100% greater risk of heterosexual transmission and 113% increased risk of progression to AIDS or death. Antiretroviral therapy continues to be unavailable or not-yet-indicated for 72% of the world’s HIV-infected persons. Mounting evidence that treatment of coinfections may reduce HIV viral load, even modestly, suggests the priority of improved adjunctive care for HIV-infected persons even without antiretroviral therapy, both to slow disease progression and to reduce infectiousness.

Editors’ note: Tuberculosis, herpes, malaria, leishmania, and helminth infections all upregulate HIV transcription. This analysis suggests that aggressively and systematically treating these coinfections in people living with HIV, preventing opportunistic infections, and assuring adequate nutrition may result in small, sustained drops in plasma HIV RNA. These measures should be instituted for all people living with HIV whether they are eligible for antiretroviral treatment or not, in the interest of reducing the likelihood of HIV transmission and slowing disease progression.