Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products. The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lymphocytes. When produced in the presence of APOBEC3G, vif-defective virus is non-infectious. APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA. APOBEC family members also have potent DNA mutator activity through dC deamination; however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown. Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA. We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.

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At 4 years, only 39% of individuals treated with HAART reached a CD4 T-lymphocyte count of 500/microL or greater, and 16% with CD4 T-lymphocyte counts less than 200/microL remained susceptible to opportunistic infections. Treatment interruptions, a poor virologic response, and older age were the major factors negatively affecting the recovery of CD4 T lymphocytes.

Background. The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)-infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration.Methods. Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load !1000 copies/mL for у5 years. CD4 T cell recovery was stratified by CD4 T cell count 5 years after initiation of ART (у500 cells/mL was defined as a complete response, and !500 cells/mL was defined as an incomplete response). Determinants of incomplete responses and clinical events were evaluated using logistic regression and survival analyses.Results. The median CD4 T cell count increased from 180 cells/mL at baseline to 576 cells/mL 5 years after ART initiation. A total of 35.8% of patients were incomplete responders, of whom 47.6% reached a CD4 T cell plateau !500 cells/mL. Centers for Disease Control and Prevention HIV-1 disease category B and/or C events occurred in 21% of incomplete responders and in 14.4% of complete responders ( ). Older age (adjusted P 1 .05 odds ratio [aOR], 1.71 per 10-year increase; 95% confidence interval [CI], 1.21-2.43), lower baseline CD4 T cell count (aOR, 0.37 per 100-cell increase; 95% CI, 0.28-0.49), and longer duration of HIV infection (aOR, 2.39 per 10-year increase; 95% CI, 1.19-4.81) were significantly associated with a CD4 T cell count !500 cells/mL at 5 years. The median increases in CD4 T cell count after 3-6 months of ART were smaller in incomplete responders ( ) and predicted, in conjunction with baseline CD4 T cell count and age, incomplete response with 80% P ! .001 sensitivity and 72% specificity.Conclusion. Individuals with incomplete CD4 T cell recovery to !500 cells/mL had more advanced HIV-1 infection at baseline. CD4 T cell changes during the first 3-6 months of ART already reflect the capacity of the immune system to replenish depleted CD4 T lymphocytes.

Drug-resistant variants are frequently present in both recently and chronically infected therapy-naive patients. Drug-resistant variants are most commonly seen in patients infected with subtype B virus, probably because of longer exposure of these viruses to drugs. However, an increase in baseline resistance in non-B viruses is observed. These data argue for testing all drug-naive patients and are of relevance when guidelines for management of postexposure prophylaxis and first-line therapy are updated.