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New Studies Offer More Insight on HIV Sexual Transmission and Prevention

A new estimate puts the likelihood of HIV transmission via receptive anal sex at 138 per 10,000 acts, but looking at probabilities over a longer period provides a better understanding of risk than per-act probabilities, according to a pair of studies in the May 6 advance online edition of AIDS. Mathematical models showed that combining prevention methods -- especially those that include antiretroviral treatment-as-prevention or PrEP -- can greatly reduce the risk of transmission.

As clinical trials of antiretroviral therapy (ART) used by HIV positive people for treatment-as-prevention or by HIV negative people for pre-exposure prophylaxis (PrEP) repeatedly demonstrate dramatic drops in transmission, researchers continue to try to pinpoint the risk of transmission from specific sex acts and other practices.

As described in the first report, Pragna Patel, Arielle Lasry, Jonathan Mermin, and colleagues from the U.S. Centers for Disease Control and Prevention (CDC) updated previous estimates of the risk of HIV acquisition from parenteral (for example, accidental needle-sticks or sharing drug injection equipment), vertical (mother-to-child during pregnancy, delivery, or breastfeeding), and sexual exposures. They also looked at the protective effect of condoms, male circumcision, and ART.

The authors performed literature searches of Medline, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Science, Global Health, the Cochrane Library, and PubMed to identify English-language studies published since a previous review in 2008. Since the last CDC estimates in 2005, new data have been reported from cohort studies of heterosexuals and men who have sex with men (MSM), and new systematic reviews and meta-analyses have been published.

Out of 7339 abstracts potentially related to per-act transmission risk, 90 were deemed relevant, and of these 14 were included in the systematic review, including 3 meta-analyses providing pooled transmission risk probabilities and 2 studies providing data on modifying factors. Out of 8119 potentially relevant abstracts on modifying factors, 15 relevant articles were identified, including 5 meta-analyses. The modifying factors included HIV viral load, acute HIV infection (when viral load is especially high), sexually transmitted diseases that cause genital ulcers, male circumcision, condom use, PrEP, and treatment -- including early ART -- as prevention.

Results

• As expected, blood transfusions posed the greatest risk of HIV transmission, at 9250 per 10,000 exposures (95% confidence interval [CI] 8900-9610).
• The next highest risk was mother-to-child transmission without antiretroviral prophylaxis, at 2255 per 10,000 exposures (CI 1700-2890);
• Sharing needles for injection drug use had a risk of 63 per 10,000 exposures (CI 41-92), while the risk from needle-sticks was 23 per 10,000 (0-46).
• Sexual exposure risks ranged from too low to quantify for oral sex, to the highest risk for receptive anal sex:

o   Receptive anal intercourse: 138 per 10,000 acts (CI 102-186);

o   Insertive anal intercourse: 11 per 10,000 (CI 4-28);

o   Receptive vaginal intercourse: 8 per 10,000 (CI 6-11);

o   Insertive vaginal intercourse: 4 per 10,000 (1-14);

o   Receptive oral sex: low (none in approximately 9000 acts) (CI 0-4);

o   Insertive oral sex: low (CI 0-4).

• Factors associated with increased transmission risk included:

o   Acute HIV infection vs asymptomatic disease: relative risk (RR) 7.25, or more than 7-fold higher risk (CI 3.05-17.30);

o   Late stage vs asymptomatic HIV disease: RR 5.81 (3.00-11.40);

o   High blood viral load: RR 2.89 (CI 2.19-3.82);

o   Genital ulcer disease: RR 2.65 (CI 1.35-5.19);

• Factors associated with lower transmission risk included:

o   Early vs delayed ART use by positive partner: RR 0.04, or 96% risk reduction (0.01-0.27);

o   ART vs no treatment for positive partner: RR 0.08 (CI 0.00-0.57);

o   PrEP - heterosexual couples: RR 0.29 (CI 0.17-0.47)

o   PrEP - men who have sex with men: RR 0.56 (CI 0.37-0.85);

o   PrEP - injection drug users: RR 0.52 (CI 0.28-0.90);

o   Condom use: RR 0.20 (CI 0.08-0.47)

o   Male circumcision - protection for heterosexual male partner: RR 0.50 (0.34-0.72);

o   Male circumcision - protection for heterosexual female partner: RR 0.80 (CI 0.53-1.36);

o   Male circumcision - protection for insertive MSM partner: RR 0.27 (CI 0.17-0.44);

o   Male circumcision - protection for receptive MSM partner: RR 1.20, a small increase in risk (CI 0.63-2.29);

• The estimated risk of sexual transmission would be reduced by 99% if serodiscordant couples both used condoms and the HIV positive partner was on ART.

"The risk of HIV acquisition varied widely, and the estimates for receptive anal intercourse increased compared with previous estimates," the researchers summarized. "The risk associated with sexual intercourse was reduced most substantially by the combined use of condoms and antiretroviral treatment of HIV-infected partners."

"Our updated estimates for both receptive and insertive anal intercourse are substantially higher than previously reported (increased 1.8 and 0.7-fold, respectively); however, the previous estimates fall within our updated CIs for these exposures," they elaborated in their discussion.

"Understanding the effects of modifying factors when estimating per-act transmission risk can better inform an individual’s personal risk and HIV-prevention efforts," they concluded. "To the extent possible, future studies of sexual per-act transmission risk should carefully consider these transmission."

10-Year Transmission Risk

The second article, by the same research team, focused on the effects of combining strategies to prevent sexual transmission. Here, they used mathematical modeling to estimate the risk of sexual transmission over 1-year and 10-year periods among heterosexual and male-male serodiscordant (mixed status) couples.

Their model was based on risk reduction levels seen in prior studies, as described above:

• 80% with consistent condom use;
• 54% with circumcision for HIV negative male heterosexual partner;
• 73% with circumcision for negative partner in a male-male couple;
• 71% with PrEP in heterosexual couples;
• 44% with PrEP in male-male couples (overall risk reduction in the iPrEx trial including participants who did not use Truvada PrEP consistently);
• 96% with ART use by the HIV positive partner (risk reduction in the HPTN 052 trial).

Over 10 years, using no protective measures at all, the risk of transmission via vaginal sex for a heterosexual couple with an HIV positive woman was estimated to be 44%. For gay male couples, the 10-year risk with no prevention reached nearly 100%.

For couples using any single prevention strategy, a substantial cumulative risk of HIV transmission remained. For a heterosexual couple, the estimated risk of transmission using only condoms for vaginal sex over 10 years was 11%. For a male-male couple using only condoms, the 10-year risk was 76%. Using only PrEP, the 10-year risk was 15% for a heterosexual couple with a positive woman, rising to 98% for gay male couples.

ART use by the HIV positive partner in a heterosexual couple was the most effective single strategy, with a 10-year risk of just 2%. Among gay male couples, however, the 10-year risk with ART alone rose to 25%, and adding consistent condom use was needed to keep the 10-year risk below 10%. An unlikely combination of PrEP, condom use, and sero-positioning (in which the negative partner does not have receptive anal sex) was required to bring the 10-year risk for gay men down to 1%.

"Modest HIV transmission probabilities per sex act translate into substantial cumulative risks over time," the authors wrote. "Focusing on 1-year and longer term transmission probabilities gives couples a better understanding of risk than those illustrated by data for a single sexual act. Long-term transmission probabilities to the negative partner in serodiscordant couples can be high, though these can be substantially reduced with the strategic use of preventive methods, especially those that include ART."

While these model estimates are based on the best available data from studies to date, they do not take viral load or adherence into account, and there is little data on anal sex among heterosexuals. In PrEP studies, for example, low overall risk reduction rates improved dramatically among participants who used the drugs as directed (from 44% to 99% among men with blood drug levels showing they took Truvada daily in iPrEx). The findings in this analysis, however, may reflect protection in "real-world" use, which is often less than perfect.

"This model was not designed to predict actual transmission risk for real-world serodiscordant couples over the course of a multiyear relationship," the authors cautioned. "Our intent is to emphasize how risk accumulates over time under various strategies and show the relative differences between strategies."

6/4/14

References

P Patel, CB Borkowf, JT Brooks, et al. Estimating per-act HIV transmission risk: a systematic review. AIDS. May 6, 2014 (Epub ahead of print).

A Lasry, SL Sansom, RJ Wolitski, et al. HIV sexual transmission risk among serodiscordant couples: assessing the effects of combining prevention strategies. AIDS. May 6, 2014 (Epub ahead of print).