Pre-infection CD8 T cells targeting HIV linked to lower post-infection viral load

The research group of Francis Plummer at the University of Manitoba was among the first to document evidence that some people can resist HIV infection despite multiple exposures. The evidence derives from a cohort of female sex workers in the Pumwani district of Nairobi; around 10% of the more than 1,000 women in the cohort have remained HIV negative despite ongoing exposures. A number of genetic and immunological factors have been described that associate with this apparent resistance to infection. [1] Among these factors are certain class I & II HLA genes and HIV-specific CD8 T cell responses (which have been detected in both the cervix and peripheral blood despite the absence of any detectable virus).

However, some of the women once thought to be resistant have seroconverted many years after first joining the cohort. In one published study, the most significant risk factor for this late seroconversion was taking a break from sex work, suggesting that at least in some women, ongoing exposure to HIV was involved in the maintenance of resistance (although the study also described some women who, after taking a break and returning to sex work, experienced an increase in their HIV-specific CD8 T cell responses and did not become infected). [2] One lingering question regarding these observations is whether women who have developed HIV-specific CD8 T cell responses prior to becoming infected are able to better control viral replication after infection occurs; in other words, does the presence of HIV-specific CD8 T cells give the immune system any kind of head start against the virus?

Although this is a difficult question to answer in a cohort study, Plummers group has now published data suggesting that pre-infection HIV-specific CD8 T cells may indeed be linked to better control of viral load post-infection. [3]

Because the numbers of people studied were small, the researchers conducted two analyses, one involving the Nairobi cohort and another with a different cohort in Kibera. In both cases, women who displayed HIV-specific CD8 T cell responses prior to infection had lower post-infection viral loads on average (by around 1 log) compared to women who lacked these responses. The researchers stress that all the pre-acquisition immunological assays were performed by investigators who were blinded to subsequent HIV acquisition status and viral load. In terms of the functionality of HIV-specific CD8 T cells between the two groups, the ability of the cells to proliferate in response to HIV antigens associated with better viral load control, while numbers of HIV-specific CD8 T cells producing the cytokine interferon gamma showed the opposite trend.

In discussing the study results, the researchers point out that while its possible that pre-infection HIV-specific CD8 T cells played a causal role in the observed outcomes, they could also represent a marker for other genetic and/or immune factors that are linked to better control of HIV replication. They nevertheless argue that their data support continued evaluation of T cell-based vaccines despite the disappointing results obtained with Mercks candidate.

3. Kaul R. HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition. Concise Communication. doi: 10.1097/QAD.0b013e3283391d40. PDF only: