No abstract

The absence of immune defects that occurs in the syndrome of long-term nonprogressive (LTNP) HIV infection offers insights into the pathophysiology of HIV-induced immune disease. The (H[F/S]RIG)2 domain of viral protein R (Vpr) induces apoptosis and may contribute to HIV-induced T cell depletion. We demonstrate a higher frequency of R77Q Vpr mutations in patients with LTNP than in patients with progressive disease. In addition, T cell infections using vesicular stomatitis virus G (VSV-G) pseudotyped HIV-1 Vpr R77Q result in less (P = 0.01) T cell death than infections using wild-type Vpr, despite similar levels of viral replication. Wild-type Vpr-associated events, including procaspase-8 and -3 cleavage, loss of mitochondrial transmembrane potential (Δψm), and DNA fragmentation factor activation are attenuated by R77Q Vpr. These data highlight the pathophysiologic role of Vpr in HIV-induced immune disease and suggest a novel mechanism of LTNP

No abstract

It has been proposed that antiretroviral therapies (ART) possess both antiviral and immunomodulatory activities when used in HIV infected patients. Few studies have addressed whether these putative immunomodulatory effects are also seen in HIV negative patients, for example, when used for post exposure prophylaxis (PEP). We chose to evaluate immunologic function in HIV negative patients who received Nelfinavir and Combivir (AZT and 3TC) as PEP. Lymphocytes from patients taken immediately before, during, and after PEP were analyzed. No changes were seen in absolute or percent CD4 or CD8 T lymphocyte numbers, nor in markers of activation, memory, or co-stimulatory molecules. Surface expression of apoptosis-related ligands and receptors were unaltered, but apoptosis susceptibility was significantly inhibited by PEP (P less than 0.05). These data confirm in vitro that apoptosis susceptibility is altered by ART, including in HIV-negative patients who take PEP.