HIV Infectivity Rises with Plasma Viral Load

Neil Osterweil

January 12, 2012

January 12, 2012 — The risk for sexual transmission of HIV-1 increases significantly as plasma viral levels of the infected individual rise, according James P. Hughes, PhD, professor of biostatistics at the University of Washington in Seattle, and colleagues, who studied HIV-1 infectivity among more than 3200 heterosexual couples in sub-Saharan Africa.

Each log10 increase in copies per milliliter of plasma HIV-1 RNA was associated with a near tripling of the per act risk for infection of the sero-negative partner in a sero-discordant couple, the researchers report in an article published in the February 2012 issue of the Journal of Infectious Diseases.

The study confirms that condoms are highly effective at reducing risk for new infections: the risk was 78% lower for couples who reported using them compared with for couples who did not.

"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.

The study "provides valuable new estimates of HIV transmission per coital act in sub-Saharan Africa," note Ronald H. Gray MD, and Maria J. Wawer, MD, PhD, from the Bloomberg School of Public Health, Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, in an accompanying editorial commentary.

HSV/HIV Prevention Trial

The investigators looked at data from a longitudinal cohort of 3297 sero-discordant heterosexual couples in sub-Saharan Africa. The couples were participants in the randomized Partners in Prevention Herpes Simplex Virus/Human Immunodeficiency Virus Transmission Study.

During approximately 2 years of follow-up, there were 86 linked HIV transmission events. In a model looking only at condom use and gender, the authors calculated that each unprotected sexual act was associated with a male-to-female transmission (MTF) risk of .0019 (95% confidence interval [CI], .0010 - .0037), and a female-to-male transmission risk of .0010 (95% CI, .00060 - .0017). Women were thus at a nearly 2-fold greater risk than men (relative risk [RR], 1.95; P = .003).

"However, after adjustment for plasma HIV-1 RNA and HSV-2 status and age of the uninfected partner (all of which differed significantly depending on the gender of the HIV-1–infected partner), the RR for MTF transmission was attenuated to 1.03 (P = .93), suggesting that the higher risk of MTF transmission was largely due to higher viral loads in men," the investigators write.

In a multivariate model, characteristics of the HIV-infected partner that were significantly associated with the likelihood of HIV-1 transmission per sexual act included plasma HIV-1 RNA (RR, 2.89 per log10 copies/mL; 95% CI, 2.19 - 3.82 P < .001) and reported condom use (RR, 0.22; 95% CI, .11 - .42; P < .001).

Characteristics of the uninfected partner that were significantly associated with transmission in the multivariate model included every 5-year increase in age (RR, 0.82; 95% CI, 0.71 - 0.94; P = .006); herpes simplex virus seropositivity at baseline (RR, 2.14; 95% CI, 1.18 - 3.88; P = .012); genital ulcer disease determined by exam or self-report during follow-up (RR, 2.65; 95% CI, 1.35 - 5.19; P = .004); Trichomonas vaginalis infection at baseline, for women (RR, 2.57; 95% CI, 1.42 - 4.65; P = .002); cervicitis or vaginitis during follow-up, for women (RR, 3.63; 9% CI, 1.47 - 8.92; P = .005); and circumcision of the male partner (RR, 0.53; 95% CI, .29 - .96; P = .037).

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.' "

The study was supported by grants from the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors and editorialists have disclosed no relevant financial relationships.

J Infect Dis. 2012;205:351-352, 358-365. Article full text, Editorial commentary full text


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