HIV transmission highest during primary infection

Rates of HIV transmission via vaginal sex are highest during primary HIV infection, according to a study conducted in Uganda and published in the May 1^st edition of the Journal of Infectious Diseases. The investigators estimated that during the early months of HIV infection, the rate of HIV transmission could be as high as one per fifty instances of vaginal sex and recommend that HIV prevention efforts should focus on identifying individuals with primary infection.

Estimates suggest that the rate of heterosexual transmission of HIV per instance of vaginal sex follows a ‘U’-shaped model, with transmission being highest soon around the period of HIV seroconversion, lower during chronic infection before increasing again during late-stage HIV infection. This model is supported by analysis of HIV plasma viral load, which is highest during early and late HIV disease and has shown to be a predictor of the risk of heterosexual HIV transmission.

There are, however, limited empirical data on the infectivity of heterosexuals with HIV. Accordingly investigators conducted a retrospective analysis including 235 monogamous, HIV discordant couples in the Rakai district of Uganda.

Study design

Recruitment took place between 1994 and 1999. All the participants were aged between 15 – 59 and were enrolled in a study into the prevention of HIV and sexually transmitted infections. Study visits were every ten months when individuals were asked to provide details of their sexual activity, including their number of sexual partners and the number of times they had vaginal sex. Tests for sexually transmitted infections were also conducted. Condoms and safer sex counselling was provided to all individuals.

Blood samples from the HIV-positive partners were tested to determine HIV viral load.

An incident HIV infection was established in 23 couples. Both partners were HIV-negative on enrollment to the study, but one partner subsequently seroconverted. These couples provided the data on infectivity in the period following HIV seroconversion. The mean period of follow-up for these couples was 17 months.

In 161 couples, one partner was identified as already being HIV-positive at enrollment and survived through a mean of 30 months of follow-up. These couples provided data on infectivity during chronic HIV infection. Finally, in 51 couples, one partner was identified as already HIV-positive on study entry and died during a mean of 27 months follow-up.

None of the men reported homosexual sex, no anal sex was reported, and no individual reported either injecting drug use or receiving blood or blood products.

The average rate of HIV transmission per act of vaginal intercourse was estimated as the number of seroconversions divided by the number of sexual acts in the follow-up period. Adjusted rate ratios were then calculated.

All individuals with early HIV transmit HIV to partners

The mean frequency of vaginal sex was 10 times per month for couples in the seroconversion and chronic infection groups, and a mean of nine acts per month for couples where one partner died in the period 16 – 25 months before death, falling to five acts per month in the six to fifteen months before death.

Five months after seroconversion individuals had a median blood viral load of 30,000 copies/ml, which had fallen to a median of 2,600 copies/ml 15 months after seroconversion. Median viral load was 10,000 copies/ml on study entry for individuals with chronic infection, increasing to 15,000 copies/ml by the end of follow-up. The final median viral load was 112,000 copies/ml for individuals who died, blood being tested a median of five months before death.

A total of 68 (29%) individuals transmitted HIV to their partners. All 23 individuals who seroconverted transmitted HIV to their partners. Of these ten (43%) did so during the first ten weeks, the other thirteen within 35 months. The average annual rate of HIV transmission was 8% for partners where a partner had chronic HIV infection. Of the individuals with later stage HIV infection 19 of 51 (37%) transmitted HIV to their partner six months to three years before their death.

Early and late stage HIV associated with increased risk of transmission

The overall HIV transmission rate per act of vaginal sex was 0.0012. The risk of transmission was highest in the first two and a half months of HIV infection at 0.0082, before decreasing to 0.0015 during the next ten months. This was not significantly different to individuals with chronic HIV infection, the rate being 0.0007 per act of vaginal sex. For individuals with late stage HIV disease the risk of HIV transmission increased significantly to 0.0036 per act of vaginal sex.

In analysis adjusted for viral load, early (risk ratio 7.23) and late stage HIV infection (risk ratio 5.81) were associated with a significantly increased risk of HIV transmission per sexual act.

Focus on identifying primary infection, say investigators

“The present analysis…provides the first empirical data on the substantial variation in transmission by stage of HIV-1 infection”, write the investigators, “after seroconversion…the rate of HIV transmission within the first 2.5 months was almost 12-fold higher than that observed in [chronic] couples. The rate then increased significantly again two years before the index partner’s death.” The investigators emphasise that “the rate of transmission per coital act may thus be very high for a short period immediately after HIV infection.

HIV treatment strategies for resource limited setting advocate providing antiretroviral therapy when an individual is already ill because of HIV. Such an approach “may have only a modest impact on HIV transmission.” The investigators conclude that prevention efforts should focus on identifying individuals with primary HIV infection, the promotion of safer sexual behaviours, and the appropriate use of antiretroviral therapy.

An editorial in the same edition of the Journal of Infectious Diseases says that the study provides a “new and important understanding of the transmission of HIV” and draws attention to the finding that “nearly one-half of the HIV transmission events observed could be ascribed to a sex partner with newly acquired HIV infection.”