Background:  A sub-population of HIV-1-infected individuals, termed elite suppressors, maintain low or undetectable plasma viral loads in the absence of HAART. Although the majority of elite suppressors have normal CD4⁺ T cell counts, we describe a subset of these patients whose CD4⁺ T cell counts decline despite low plasma viral load. These patients present considerable clinical difficulties regarding when to initiate HAART and how to monitor response. It is unclear why CD4⁺ T cell counts decline in the absence of significant viremia. We hypothesize that low plasma viral loads in these patients may result from low proviral loads in the blood, and that ongoing viral replication may be occurring in another compartment. It may also be the case that virus is cleared from the blood following binding of neutralizing antibody.

Methods:  Elite suppressors were defined as HIV-1-infected patients with plasma viral loads of <1000 copies/mL in the absence of HAART. This cohort was divided into those with normal CD4⁺ T cell counts and those with declining or low CD4⁺ T cell counts (<450 cells/mm³). Viral clade was determined by sequence analysis of the provirus. Proviral loads were measured using a novel quantitative real-time HIV-1 proviral DNA polymerase chain reaction (PCR). Simultaneous quantification of a single copy cellular gene allows proviral loads to be expressed per CD4⁺ T cells ´10⁶. The presence of neutralizing antibodies was determined by testing for inhibition of infection of CD4⁺ cells following incubation with a panel of HIV-1 viruses.

Results:  From a cohort of 69 elite suppressors, 15 were found to have low or declining CD4⁺ T cell counts. In this subset, median plasma viral load was 227 copies/mL (39 to 966) and median CD4⁺ T cell count was 319 cells/ mm³  (81 to 435). Unexpectedly, proviral loads were not lower than those found in the control group.

Conclusions:  Proviral loads in elite suppressors with declining or low CD4⁺ T cell counts were not lower than in the control group. This indicates that viral replication was ongoing in the blood of these patients.