Infrequent recovery of HIV from but robust exogenous infection of activated CD4(+) T cells in HIV elite controllers.

BACKGROUND. Human immunodeficiency virus (HIV) elite controllers are able to control infection with HIV-1 spontaneously to undetectable levels in the absence of antiretroviral therapy, but the mechanisms leading to this phenotype are poorly understood. Although low frequencies of HIV-infected peripheral CD4(+) T cells have been reported in this group, it remains unclear to what extent these are due to viral attenuation, active immune containment, or intracellular host factors that restrict virus replication. METHODS. We assessed proviral DNA levels, autologous viral growth from and infectability of in vitro activated, CD8(+) T cell-depleted CD4(+) T cells from HIV elite controllers (mean viral load, <50 copies/mL), viremic controllers (mean viral load, <2000 copies/mL), chronic progressors, and individuals receiving highly active antiretroviral therapy. RESULTS. Although we successfully detected autologous virus production in ex vivo activated CD4(+) T cells from all chronic progressors and from most of the viremic controllers, we were able to measure robust autologous viral replication in only 2 of 14 elite controllers subjected to the same protocol. In vitro activated autologous CD4(+) T cells from elite controllers, however, supported infection with both X4 and R5 tropic HIV strains at comparable levels to those in CD4(+) T cells from HIV-uninfected subjects. Proviral DNA levels were the lowest in elite controllers, suggesting that extremely low frequencies of infected cells contribute to difficulty in isolation of virus. CONCLUSIONS. These data indicate that elite control is not due to inability of activated CD4(+) T cells to support HIV infection, but the relative contributions of host and viral factors that account for maintenance of low-level infection remain to be determined.

Transient treatment exclusively containing nucleoside analogue reverse transcriptase inhibitors in highly antiretroviral-experienced patients preserves viral benefit when a fully active therapy was initiated.

BACKGROUND: We determined whether coformulated zidovudine/lamivudine/abacavir plus tenofovir could maintain immune status in comparison with a genotype-guided salvage regimen in highly pretreated patients. METHOD: This was a randomized pilot control-arm study. The primary endpoint was the proportion of patients who maintained their CD4+ T-cell count at Week 48. RESULTS: Thirteen patients were randomized to the study arm and 10 to the control arm. At 48 weeks, 8 (64%) patients in the study arm and 10 (100%) in the control arm maintained their immune status (p = .09). No new AIDS-defining events occurred. Three patients (27%) in the study arm and 5 (50%) in the control arm achieved an undetectable viral load (p = .39). When a fully suppressive regimen was initiated, 69% of patients in the study arm (9 patients) and 60% (6 patients) in the control arm reached <50 copies at 96 weeks (p = .98). CONCLUSION: Although no statistically significant differences in immunological course were observed between the arms, the control group achieved better results after 48 weeks. This transient therapy could be reserved for specific patients in whom the risk of incomplete adherence or toxicity compromises efficacy while they are awaiting a fully active drug, without jeopardizing viral efficacy when a fully suppressive regimen is initiated.