CMV infection may contribute to the size of the latent HIV reservoir

The presence of cytomegalovirus (CMV) in blood and semen is associated with higher levels of HIV DNA in blood, investigators from the United States report in the online edition of Journal of Infectious Diseases. The study involved gay men recently infected with HIV. The authors believe that CMV replication may increase the reservoir of cells latently infected with HIV.

“This study demonstrated that presence of CMV in PBMC [peripheral blood mononuclear cells] and in seminal plasma of HIV infected ART-naïve MSM was associated with higher levels of proviral HIV DNA,” write the authors. “It also found that simultaneous detectable CMV in semen and PBMC was associated with the highest levels of HIV DNA in PBMC.”

Over 75% of HIV-positive gay men have at least one herpes virus actively replicating in their semen and the most common is CMV. Co-infection with CMV has been associated with accelerated HIV disease progression and increased immune activation. Investigators from San Diego hypothesised that it could also be an important factor in determining the size of the reservoir of cells with latent HIV infection.

They therefore designed an observation study involving 113 gay men recently infected with HIV. None were taking antiretroviral therapy. Paired semen and blood samples were provided for analysis. CMV DNA was quantified, as was proviral HIV DNA in PBMC, HIV viral load and CD4 cell count.

The participants had been infected with HIV for a median of 70 days at baseline. Median CD4 cell count at this time was 523 cells/mm³ and median blood plasma viral load was 50,000 copies/ml. Approximately 46% of participants provided semen samples positive for CMV (median peak viral load 4.52 log₁₀ DNA copies/ml).

Just over half the cohort (52%) provided paired longitudinal samples for analysis (median follow-up, 67 days). Approximately a fifth had intermittent CMV shedding in semen and 10% had intermittently detectable CMV DNA in PBMC. HIV DNA was detected in 91% of PBMC samples.

Analysis of the entire cohort showed that higher levels of HIV in DNA were associated with longer duration of HIV infection, and the presence of CMV in PBMC.

However, blood plasma viral load and CD4 cell count were not associated with HIV DNA levels. The investigators were surprised by this finding and performed two sub-analyses. The first excluded participants with low-level HIV DNA. This revealed a positive association between HIV viral load and HIV DNA (p = 0.01). The second excluded participants with an estimated duration of infection of up to 120 days. This showed no association between HIV viral load and HIV DNA. Nor was the presence of a sexually transmitted infection at baseline associated with HIV DNA levels.

In multivariate analysis, the association between CMV in PBMC and higher levels of HIV DNA in PBMC was significant (p = 0.05).

Participants with detectable CMV in both semen and PBMC were more likely to have higher HIV DNA levels in PBMC than individuals with undetectable CMV in both semen and PBMC (p = 0.02).

“This study provides important insights in regard of one possible mechanism contributing to the establishment of the viral reservoir during early HIV infection,” the investigators conclude. “Future studies should determine if persistent CMV replication can be targeted as a strategy to reduce the size of the latent HIV reservoir.”