Viral load in semen, cervico-vaginal fluid and rectal secretions

While researchers are in general agreement that viral load in blood and in other body fluids (such as semen, cervico-vaginal fluids and rectal secretions) are highly correlated, and most people on successful treatment will have a reduced viral load in both their blood and sexual fluids, the correlation is not perfect.

This may be due to:

• Antiretroviral drug levels not being high enough, due to a variety of factors including adherence, absorption, drug-drug interactions, and resistance.
• Inflammation caused by sexually transmitted infections.
• In women, HIV subtype and menstruation.

This means that a proportion of people who have undetectable viral loads according to blood tests may still be infectious.

In the largest study of its kind to date, a sub-study of the Partners in Prevention trial undertaken by Baeten and colleagues,¹ cervico-vaginal and seminal viral load were measured in 2521 HIV-positive participants. They calculated the impact of these viral loads on the risk of HIV transmission and compared this to actual observed transmissions in the study.

Cervical samples from 1805 women, including 46 who apparently transmitted HIV to their partner, and semen samples from 716 men, including 32 who apparently transmitted HIV to their partner, were tested. Each tenfold increase in genital viral load was associated with a 2.2-fold increase in the likelihood of transmission by women, and a 1.8-fold increase in the likelihood of transmission by men.

After adjusting for blood plasma viral load, genital viral load was found to be independently associated with the risk of transmission. Irrespective of the influence of viral load in the blood, there was still an additional 70% increased risk in the chance of transmission per tenfold increase in genital viral load. This suggests that measuring genital viral load would be a better guide to the likelihood of transmission than viral load in blood.

However, the study also found that genital viral load was more often undetectable than blood plasma viral load, and that there were seven female-to-male and four male-to-female HIV transmissions from people with undetectable genital viral load but detectable HIV in their blood. Conversely, there were no transmissions from participants with an undetectable viral load in blood and detectable genital viral load.

These conflicting results are probably due to the time lag between the time of infection and taking the viral loads in the genital fluids of people who transmitted. It is likely that genital viral load varies more quickly or unpredictably than blood plasma viral load, so that the association between viral load and infectiousness did not show up in the study.

Another recent study suggests that women not taking treatment who have subtype C virus have significantly higher viral load in their cervico-vaginal fluid than women with subtype B. It also found that women taking treatment who have either subtype B or C are more likely than men to have detectable virus in the genital tract even when viral load is undetectable in the blood.²

Subtype C is found primarily in sub-Saharan Africa, India, and Brazil, and in people who have moved from these regions. Subtype B is found primarily in west and central Europe, the Americas, Australia, South America, and several southeast Asian countries (Thailand, and Japan), northern Africa and the Middle East, as well as in people who have moved from these regions.

The study included 158 men and 170 women in seven different countries (Brazil, India, Malawi, Peru, South Africa, United States and Zimbabwe) who started treatment with three different combinations of antiretroviral drugs, and had viral load in blood plasma and genital fluids measured at baseline and again after 48 and 96 weeks of treatment.

Women with subtype C infection had the highest genital tract viral load at baseline, a median of approximately 125,000 copies/ml. This compared to a median baseline genital tract viral load of 10,000 copies/ml for women with subtype B infection; 10,000 copies/ml for men with HIV subtype C and 6000 copies/ml for men with subtype B infection.

Although antiretroviral therapy was highly effective at suppressing viral load in blood in women and men with both subtypes, there were significant gender differences in genital tract viral load with a lower proportion of women (84% versus 97% of men) sustaining an undetectable genital tract viral load by week 96. The researchers believe that this might be explained by differences in genital tract drug penetration associated with physiological differences between men and women.