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HIV Viral Load Predicts Risk of Infection in Large Study

HIV RNA levels are the most significant factor predicting risk of HIV transmission, according to a study reported in the February 1, 2012, Journal of Infectious Diseases. Condom use, adult male circumcision, and concurrent sexually transmitted infections (STIs) were also important factors.

Over the past few years the field of biomedical HIV prevention has seen a number of breakthroughs. Large, well-designed studies have produced impressive results showing that, particularly among heterosexual couples, antiretroviral treatment as prevention, pre-exposure prophylaxis (PrEP), and male circumcision can all significantly reduce the risk of sexual transmission of HIV. Even areas like microbicides and therapeutic vaccines (which have produced both hopeful and disappointing results) are showing hints of potential.

Probably the most significant of these recent studies was the HPTN 052 trial, results of which were presented at the International AIDS Society conference in Rome in July 2011 and published in the August 11, 2011, New England Journal of Medicine.

HPTN 052 compared the risk of transmission among serodiscordant (one HIV positive, the other HIV negative) heterosexual couples when the HIV positive partner was randomly assigned to receive or defer antiretroviral therapy (ART). The study found a remarkable >90% reduction in HIV transmission among those who started immediate ART compared with those who delayed treatment until their CD4 T-cell count fell below 250 cells/mm³. When treatment adherence was factored in, the level of protection neared 100%.

While exciting, such research must be validated by other studies. One such study, reported in the current issue of the Journal of Infectious Diseases, found that HIV RNA level (commonly referred to as viral load) is the most powerful predictor of the risk of genetically linked HIV transmission among heterosexual couples in Africa.

James Hughes from the University of Washington and colleagues with the Partners in Prevention HSV/HIV Transmission Study Team looked at HIV transmission among serodiscordant heterosexual couples.Thestudy was originally designed to determine whether the use of acyclovir to suppress herpes simplex virus type 2 (HSV-2) would reduce HIV transmission; results showed that acyclovir had no significant effect on HIV infection rates.

The present analysis followed 3297 HIV serodiscordant couples enrolled at 14 sites in eastern and southern Africa. At the beginning of the study the average age was 32 years, 67% of the HIV positive partners were women, and 34% of the HIV positive male partners were circumcised. The average HIV RNA level was 3.91 log₁₀, or about 8000 copies/mL.

Couples were followed for up to 2 years. Participants were regularly tested for HIV viral load, genetically linked HIV transmission (the newly infected person had the same strain as his or her HIV positive partner), and presence of STIs. Couples were also asked to report on condom use.

Results

• Overall, there were 86 genetically linked HIV transmissions during the follow-up period.
• HIV transmission occurred in approximately 1 out of 900 coital events.
• Unadjusted risks of unprotected intercourse were 0.0019 for male-to-female (M-F) transmission and 0.0010 for female to male (F-M) transmission.
• The relative risk of M-F vs F-M HIV transmission was 1.03 after adjusting for HIV RNA, HSV-2 status, and age.
• Each 1 log₁₀ increase in HIV RNA was associated with a 2.9-fold rise in the risk of HIV transmission.
• Self-reported condom use reduced transmission risk by 78%.
• Presence of genital ulcer disease (GUD) increased risk of transmission by 2.65 times.
• Male circumcision reduced the risk of transmission by approximately half.

This study adds to the growing body of evidence that viral load is a crucial factor in HIV transmission. It follows that expanding HIV treatment -- which reliably reduces HIV RNA levels -- can be expected to decrease the number of new infections. With roughly 2 new infections occurring worldwide for each person who starts ART, the need for effective prevention strategies is particularly acute.

While important and encouraging, these results are hardly a surprise. In nearly all infectious diseases, there is a strong correlation between pathogen load and the risk of transmission. The presence of coinfections, particularly those resulting in inflammation, also tend to increase infection risk.

Nonetheless, the Partners in Prevention findings, along with the recent results from HPTN 052, iPrEx, TDF2, and Partners PrEP, show that a range of biomedical prevention tools -- including treatment as prevention and PrEP -- can be powerful weapons along with behavioral interventions such as condom use in the HIV prevention armamentarium.

Investigator affiliations: Department of Biostatistics, Department of Medicine, Department of Global Health, Department of Pediatrics, Department of Epidemiology, and Department of Laboratory Medicine, University of Washington, Seattle, WA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Perinatal HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa; Department of Obstetrics and Gynecology, University of Nairobi and Kenyatta National Hospital, Kenya; Rwanda-Zambia HIV Research Group (RZHRG), Ndola, Zambia.

1/17/12

References

JP Hughes, JM Baeten, JR Lingappa, et al (Partners in Prevention HSV/HIV Transmission Study Team). Determinants of Per-Coital-Act HIV-1 Infectivity Among African HIV-1–Serodiscordant Couples.  Journal of Infectious Diseases 205(3):358-365 (free full text). February 1, 2012.

RH Gray and MJ Wawer. Probability of Heterosexual HIV-1 Transmission per Coital Act in Sub-Saharan Africa. Journal of Infectious Diseases 205(3):351-352 (free full text). February 1, 2012.