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Is HIV Transmission Risk Really Near Zero If HIV+ Heterosexual Partners Are on ART?


Serodiscordant heterosexual couples in which the positive partner has been on combination antiretroviral therapy (ART) for more than 6 months may have an HIV transmission risk as high as 13 per 100,000 sex acts -- but the risk could also be zero -- according to an estimate based on a systematic review described in the April 9 online edition of Clinical Infectious Diseases.

Studies have shown that effective antiretroviral treatment dramatically lowers the risk of HIV transmission. In the HPTN 052 study, sexual transmission was reduced by 96%when HIV positive partners in serodiscordant (mixed-status) heterosexual couples started ART immediately upon diagnosis rather than waiting for their CD4 count to fall. More recently, the PARTNER studysaw no cases of transmission among heterosexual and gay male serodiscordant couples when the positive partner was on ART with a viral load below 200 copies/mL.

While studies such as these provide information about statistical risk of transmission on a population level, they cannot predict outcomes in individual cases, and the risk of transmission during a single act of condomless sex with an HIV positive partner on ART remains unknown, according to the authors' background information.

Virginie Supervie from Sorbonne Université in Paris and colleagues performed a systematic medical literature review looking for studies of HIV transmission among serodiscordant heterosexual couples in which the infected partner was on combination ART with regular viral load monitoring.

They identified 6 relevant studies meeting the inclusion criteria that reported data on HIV incidence, viral load of the positive partner, condom use, and sexual activity. Included couples had sex 3-12 times per month, on average, and reported using condoms about 80% of the time.

The authors used Bayesian statistics to combine data from these studies to estimate the per-act risk of HIV transmission through condomless sex among serodiscordant couples with the HIV positive partner on combination ART for more than 6 months.


  • A total of 4 cases of genetically linked transmission -- in which the newly infected person had the same strain of HIV as their partner -- were reported among 1672 serodiscordant couples with the positive partner on ART.
  • At least 3 cases of transmission occurred when the positive partner had been on ART for less than 6 months.
  • The remaining case occurred within the first year on ART, but data were not adequate to determine whether it happened before or after 6 months.
  • Over an estimated 113,480 sex acts -- of which 17% were not condom-protected -- there was at most 1 case of transmission in which the positive partner had been on ART for more than 6 months.
  • The estimated upper-bound per-act risk of HIV transmission was 8.7 per 100,000 sex acts if this transmission occurred before 6 months on ART.
  • The upper-bound risk estimate rose to 13 per 100,000 sex acts if this transmission occurred after 6 months on ART.

"Available data do not support zero risk of HIV transmission under combination ART," the study authors wrote. "The per-act risk of HIV transmission through unprotected sex with HIV-infected individuals on combination ART in comprehensive care for >6 months (whether or not virally suppressed) is <13 [per] 100,000."

However, the number of HIV transmissions from positive partners on combination ART for more than 6 months could be much lower than 13. "Failure to observe transmission events does not exclude the possibility of HIV transmission, yet indicates a low risk, which in theory could be even zero," they wrote.

Obtaining an upper-bound risk estimate below 1 transmission per 100,000 sex acts would require observing no cases of transmission while collecting more than 12 times the amount of data -- information on 300,000 unprotected sex acts or more than 1 million mostly protected sex acts, the researchers calculated. "Estimating a 10-fold lower upper-bound risk may be unfeasible due to high condom use among HIV-serodiscordant couples in most research studies."

"Our findings provide key information for patient counseling on 
HIV transmission risk and preventive care," they concluded. "Even though it is small, the risk of transmission cumulates with the number of exposure[s] and may represent a major long-term concern. Combining several prevention methods may offer optimal protection against HIV transmission."



V Supervie, JP Viard, D Costagliola, et al. Heterosexual Risk of HIV Transmission Per Sexual Act Under Combined Anti-Retroviral Therapy: Systematic Review and Bayesian Modeling. Clinical Infectious Diseases. April 9, 2014 (Epub ahead of print).