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Viral Load Key to HIV Transmission
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HIV transmitted 1 in 900 times couple has unprotected sex; the study, which focused on almost 4000 heterosexual couples in Sub-Saharan Africa, mathematical risk depends on the viral load level of the infected sex partner.

· Risk dependent on concentration of virus in blood

· Supports use of anti-retroviral medication

· "Our results underscore the importance of antiretroviral therapy, and, possibly, treatment of coinfections, to reduce plasma HIV-1 viral load in HIV-1-infected partners, and condom promotion, male circumcision, and treatment of symptomatic [sexually transmitted infections] for HIV-1-uninfected partners as potential interventions to reduce HIV-1 transmission," the authors write.

· In their commentary, Dr. Gray and Dr. Wawer note that the investigators looked only at infectivity during latent-stage disease, "and were unable to measure transmission during early or late stages of HIV disease, which is associated with higher infectivity per coital act." They also noted that the trial from which the data were drawn excluded HIV-infected partners who had CD4 counts lower than 250 cells/mL, and that participants whose CD4 counts declined below that level during the trial received antiretroviral drugs. They conclude that "the study by Hughes et al has added to our empirical knowledge, but much about transmission probabilities per sex act remains, in the words of Winston Churchill, 'a riddle wrapped in a mystery inside an enigma.' "

A heterosexual person infected with HIV will transmit the virus to their partner once in every 900 times they have unprotected sex, say scientists.

And the risk significantly increases if the person infected has a higher concentration of the virus in their bloodstream. The best way to reduce the risk of HIV transmission is to lower the amount of the virus in the blood.

Results, from the largest study of its kind, showed for every tenfold increase in concentration, there was around a threefold increase in the likelihood of HIV transmission.

The findings support the use of anti-retroviral medications that work by lowering the concentration of HIV in the bloodstream.

Men were about twice as likely to transmit HIV to women as women were to men.

Condoms were reported to be used in 93 percent of sexual acts, but the researchers suspect their use was overreported. Therefore, condoms actually may be even more effective at preventing HIV transmission than the 78 percent reduction that the researchers estimated, Hughes said.

The study relied on self-reports, which might be wrong. However, errors in reports of the number of sexual acts would be unlikely to affect most of the study results, Hughes said.

That's because the participants included in the study are couples that have remained together and discordant over a long period of time. This indicates the couples might have some biological protection against transmission, "The true estimation might be higher if you were studying different kinds of people," Cohen said.the findings only apply to heterosexual couples, and not men who have sex with men, a group that is likely to have a much higher transmission rate, Hughes said.

By Kurt Ullman, Contributing Writer, MedPage Today

Published: January 12, 2012

Action Points

· This study found that HIV-1 viral load in the blood is one of the most important factors influencing transmission to the partner in serodiscordant African couples.



· Note that condom use reduced infectivity by 78%, although there were 56 transmission events in which the couples reported 100% condom use.

HIV-1 viral load in the blood is one of the most important factors influencing transmission to the partner in serodiscordant African couples, according to the results of a recent study.

Each log10 increase in plasma HIV-1 RNA was associated with a 2.9-fold increase in the per-act risk of transmission (95% CI 2.2 to 3.8) reported James P. Hughes, PhD, from the University of Washington in Seattle, and colleagues.

The unadjusted pre-act risk of unprotected male-to-female transmission (MTF) was 0.0019 (95% CI 0.0010 to 0.0037). The unadjusted risk for female-to-male (FTM) transmission was 0.0010 (95% CI 0.00060 to 0.0017) in the study, which was published online in the Journal of Infectious Diseases.

Increasing knowledge about HIV infectivity and the factors that affect it can help in the design of prevention measures and in modeling disease spread. This study is the first to look at HIV-1 infectivity following adjustments for time variances in plasma RNA.

The researchers enrolled 3,297 couples from the Partners in Prevention Herpes Simplex Virus/Human Immunodeficiency Virus Transmission Study. When entered into the study, both participants were tested for sexually transmitted infections. The men were examined for circumcision status and the uninfected partner's herpes simplex virus (HSV) status was determined.

Plasma HIV-1 RNA in the infected partner was obtained at enrollment, and at three, six, and 12 months, with a final test at study exit (usually around 24 months). At each quarterly visit, the uninfected partner was checked for seroconversion. Participants were counseled on HIV prevention measures, received quarterly treatment for sexually transmitted infections, and were given a supply of condoms.

Information on the number of sex acts came from monthly interviews with both partners. They were asked about total number of sex acts with the study partner, both with and without a condom, since the last visit. Since it would not be possible get information on serostatus from nonstudy partners, any sex acts occurring with nonstudy partners were not included in the analysis.

Overall, 86 transmission events were seen during the follow-up time period. After adjusting for various confounders, the relative risk for MTF transmission was reduced to 1.03 (P=0.93), suggesting that this was largely related to higher viral loads in men.

In a multivariate model, plasma HIV-1 RNA and condom use reported by infected partner combined with age, HSV-2 status, genital ulcer disease by exam or self-report, T. vaginalis at enrollment, cervicitis or vaginitis during follow-up, and circumcision status of the male partner were significant.

Circumcision in male uninfected partners was associated with significantly lower infectivity (RR: 0.53, 95% CI: 0.29 to 0.96). Condom use reduced infectivity by 78% (RR: 0.22, 95% CI 0.11 to 0.42). The protective effects of condom use were similar if the infected partner was male (RR: 0.14) or female (RR:0.29, P for gender by condom use interaction=0.29). Still, there were 56 transmission events in which the couples reported 100% condom use.

A limitation noted by the authors is the difficulty in measuring the number of sex acts between tests. This imprecision can come from a number of sources, such as overreporting; in addition, the lag between infection and detection may skew the number of acts over the period of interest.

"Observed differences in MTF and female-to-male (FTM) infectivity appear to be largely driven by measurable differences in plasma viral load of the HIV-1-infected partner, condom use, and HSV-2 status and age of the uninfected partner," wrote the authors. "This strong dependence of HIV-1 infectivity on co-factors suggests that the relationship of (unadjusted) MTF and FTM infectivity may vary substantially across different settings with different distribution of these key factors."

The study provided valuable information on estimates of transmission per coital act in sub-Saharan Africa, Ronald H. Gray MD, MSc, and Maria J. Wawer, MD, MHS, from the Johns Hopkins University Bloomberg School of Public Health wrote in an accompanying comment.

However, they did express concerns about the study's ability to look at infectivity only in latent-stage disease. The researchers were unable to measure transmission during early or late stages, which are associated with higher infectivity per act in some studies.

They also note that the group had couples counseling and high rates of condom use. This would impact on the generalizability to other areas where counseling and condoms may not be as available.

"The study by Hughes, et al. has added to our empirical knowledge, but much about the transmission per sex act remains, in the words of Winston Churchill, 'a riddle wrapped in a mystery inside an enigma'," they wrote.

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