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Antiretroviral Therapy Does Not Always Fully Suppress HIV in Semen

HIV positive men who have sex with men may continue to have detectable virus in their semen despite being on combination antiretroviral regimens that suppress blood plasma viral load, according to a report in the March 23, 2012, advance online edition of AIDS.

"Treatment as prevention" has become a key principle of biomedical prevention over the past few years, with growing evidence that effective antiretroviral therapy (ART) dramatically lowers the risk of transmitting HIV -- at least among serodiscordant heterosexual partners.

In 2008 the Swiss Federal Commission for HIV/AIDS sparked controversy when they issued a statement reading, "An HIV-infected person on antiretroviral therapy with completely suppressed viremia...is not sexually infectious." The commission emphasized that the statement only applied to vaginal intercourse between heterosexual partners when neither had other sexually transmitted infections (STIs) and the positive person had a stable undetectable viral load on ART for at least 6 months.

But what about men who have sex with men (MSM)?

Joseph Politch from Boston University School of Medicine and colleagues looked at the presence of HIV shedding in the semen of MSM on stable combination ART, and its relationship to several clinical, behavioral, and biological variables.

As background, the study authors noted that there is a "resurgent" HIV epidemic among gay and bisexual men in the ART era. Sexually transmitted infections such as gonorrhea and chlamydia may promote genital HIV shedding and transmission in this population despite antiretroviral treatment.

The study enrolled 101 sexually active HIV positive men who received care at Fenway Health, a Boston clinic that specializes in care of gay, lesbian, bisexual, and transgender people. Most (74%) were white and the median age was 43 years.

Participants were on a stable ART regimen for at least 3 months; 80% had been on ART for more than a year. They had well-preserved immune function, with a median CD4 T-cell count of 513 cells/mm³. About three-quarters were considered at high-risk for STIs, meaning they reported unprotected intercourse during the past 3 months; 9 men had active herpes simplex virus type 2 (HSV-2) or other STIs or urethritis, 24% had genital inflammation, and 63% were HSV-2 antibody positive.

The researchers measured HIV levels in paired blood and semen samples collected at the same time. Clinical and behavioral information was obtained from medical records and questionnaires.

Results

• Overall, HIV was detected in 18 out of 101 blood plasma samples (18%) and 30 out of 101 semen samples (30%).
• Men with detectable blood viral load were significantly more likely to have detectable HIV in semen.
• However, among 83 men with undetectable HIV in their blood, 25% had HIV in their semen.
• Semen viral load levels ranged from 80 to 2560 copies/mL.
• In a univariate analysis, detectable HIV in semen was significantly associated with STI risk:
  • 5% for the low-risk group;
  • 32% for the high-risk group;
  • 75% for the group with STIs or urethritis.
• Detectable semen HIV was highly associated with presence of leukocytes and neutrophil count in the semen.
• HIV in semen was also associated with elevated concentrations of seminal inflammatory markers including TNF-alfa, interleukin 6 (IL-6), IL-8, and SLPI.
• Behavioral factors associated with HIV in semen were unprotected insertive anal sex, especially with an HIV positive partner.
• Duration of ART, current antiretroviral regimen, use of a protease inhibitor, CD4 cell count, and circumcision status were not predictive of HIV in semen.
• In a multivariate analysis, the following were independent predictors of detectable semen viral load:
  • Having an STI or urethritis: odds ratio (OR) 29.03, or 29 times more likely (P = 0.003);
  • High semen TNF-alfa levels: OR 13.97 (P = 0.0003);
  • Unprotected insertive anal sex with an HIV positive partner: OR 7.34, or 7-fold higher risk (P = 0.007).

"STIs and genital inflammation can partially override the suppressive effect of [ART] on seminal HIV shedding in sexually active HIV-infected MSM," the study authors concluded. "Low seminal HIV titers could potentially pose a transmission risk in MSM, who are highly susceptible to HIV infection."

The 25% prevalence of semen HIV shedding among men with undetectable blood viral load in this study was higher than the 2%-3% prevalence reported in other large studies of HIV positive men on ART, which the authors suggested was "likely due to the high prevalence of STIs and genital inflammation in our sexually active MSM cohort."

"Our study provides evidence that genital infections and inflammation are common in HIV-infected MSM that engage in unprotected intercourse, and that these factors can promote compartmentalized shedding of HIV in the genital tract of men on suppressive HAART therapy," they summarized.

Using a highly sensitive assay, the researchers found that cell-free HIV RNA and HIV-infected cells were each detected in 13% of men with detectable blood viral load, but only 1 of 21 participants with detectable semen HIV had both forms of virus. "This provides further evidence that cell-free and cell-associated HIV in semen may arise from different sources," they wrote.

Even though the semen viral levels were quite low at 80-2560 copies/mL -- well below those of men not on ART -- the authors suggested that this could still "represent an infectious innoculum in MSM since rectal intercourse is an especially effective route of HIV transmission."

The association between detectable semen HIV and unprotected insertive anal sex, along with the high numbers of HIV target cells in the urethra, led them to suggest that "the urethra may be a primary HIV infection site."

"HIV-infected men who engage in unprotected intercourse may use [ART] and viral load status in their sexual decision-making, and being on [ART] or having an undetectable blood viral load may relax concerns about transmitting HIV...MSM at risk for transmitting HIV may believe that they have a low risk based on incorrect assumptions that [ART] eliminates HIV from semen," the authors cautioned. "Until more information on transmission risk in MSM is available, it would be prudent to advise sexually active HIV-infected MSM to use condoms and other risk-reduction strategies throughout all stages of HIV disease regardless of HIV treatment status, and to promote the aggressive diagnosis and treatment of STIs."

Investigator affiliations: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, MA; The Fenway Institute, Fenway Community Health, Boston, MA; Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, PA; Departments of Medicine and Community Health, Warren Alpert Medical School of Brown University, Providence, RI.

3/27/2012

Reference

JA Politch, KH Mayer, SL Welles, et al. Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men. AIDS. March 23, 2012 (Epub ahead of print).