HIV acts as a ‘natural immunogen’, keeping anti-HIV-1 immune responses boosted in HIV-infected male couples who have unprotected sex, say University of California San Francisco researchers (PLoS Pathog 2008; 4:e1000185).
Until now, little has been reported on the consequences of continued exposure to HIV in people who are already infected. But serosorting, the practice of identifying sexual partners based on their HIV status, is a growing trend. It often leads to unprotected sex between HIV-infected individuals, which poses the risk of acquiring a drug-resistant strain of the virus.
To shed light on the immunological consequences of continued exposure to HIV, Christian Willberg and colleagues studied 49 men, from a San Francisco prospective cohort of couples in long-term relationships, who were suppressing their virus below the detection level (50 RNA copies/ml) with HAART. Twenty-nine men had partners whose virus was also in check due to antiviral therapy, whereas 20 men had viremic partners whose viral loads were more than 90 000 RNA copies/ml.
Using enzyme-linked immunosorbent spot (ELISPOT) assay to compare HIV-1-specific T-cell responses between the two groups, the researchers found significantly stronger (P = 0.001) responses against HIV-1 protease, reverse transcriptase, and integrase peptides in the men with viremic partners. The magnitude of their responses correlated with a greater frequency of unprotected sex, and in particular with the frequency of exposure through receptive (versus insertive) anal sex. No similar correlations were found in the men with nonviremic partners.
‘Rather than losing responses because their own virus has been suppressed by antiviral therapy,’ explains Willberg, ‘we found that the men are maintaining a response because they are constantly being exposed to their partner's virus.’
That the amount of exposure drives the boosted HIV-1-specific immune responses was also illustrated in three individuals from the viremic partner group whose T-cell responses dropped significantly a year later. Two had partners who started antiretroviral therapy and were suppressing their viral loads. The third had reduced his exposure. (Seven individuals from the viremic partner group had blood samples available from a 1-year follow up.)
The researchers note that superinfection is the most likely mechanism to maintain or boost the HIV-1 immune responses. However, HIV-1 sequencing of all participants in the study found no evidence of superinfection at the systemic level in which a new virus overgrows the existing strain. Willberg, who is now at Oxford University, cautions that the study's phylogenetic analysis does not rule out localized superinfections in the gut, most likely the rectum.
Furthermore, no one knows whether maintaining a high T-cell response is good or bad. Willberg says that keeping an active HIV-1 immune response might help control viral rebound in a person when antiviral therapy fails for some reason, or it could indicate a compartmentalized superinfection and the increased risk of acquiring a drug-resistant strain. ‘It could be a double-edged sword,’ he says.