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The majority of infection by the human immunodeficiency virus (HIV-1) across the world occurs by heterosexual transmission and is likely mediated by virus present in genital secretions. In spite of this, infection is followed by clinical markers of the virus present in blood, which may not be representative of the virus involved in transmission. In fact, several studies have demonstrated that the genital tract represents a unique compartment for the virus. We assessed the relationship between immune system integrity, represented by CD4+ T cell counts, and the maintenance of viral compartmentalization between plasma and vaginal fluid virus in treatment naïve women from the Dominican Republic infected by the heterosexual transmission route. We cloned and sequenced cell free virus from plasma and genital fluid samples from six women to assess viral evolution, phylogenetic relatedness, and calculated co-receptor use for the C2V3 region of the envelope. Our analyses demonstrated plasma and vaginal fluid virus compartments remained intact only in samples from women with CD4+ T cell counts over 350 cells/μl. The majority of viral forms were predicted to use the CCR5 co-receptor, although several dual tropic forms were also identified. None of the clones were found to use the CXCR4 co-receptor even though many of the patients showed severe disease. Our findings lend further support to the role of an intact immune system in maintaining compartmentalization across blood and genital quasispecies and provide a compelling rationale to specifically consider genital tract viral forms in therapeutic and vaccine research., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Two HIV-infected individuals were followed for changes in the first exon of Tat. Plasma virus collected at 2 months after commencement of highly active antiretroviral therapy (HAART) was compared with the virus collected before initiation of HAART. This short-term therapy significantly reduced the plasma viral burden and also helped modest CD4 recovery in the blood. One of the two individuals (ACG) showed only one form of the Tat before commencement of HAART whereas five different forms (including a form identical to the pre-HAART sample) were found in the post-HAART sample. Some of the post-HAART clones showed a difference of 12.8% suggesting that the source of virus replication might be a reservoir. In the other patients multiple variants of the virus were found within each time point and also between two time points. This patient also showed a debilitating mutation (25-C/R) in three clones suggesting that some of the post-HAART viral forms were not viable in this patient. The dS/dN ratios in the patients were >2 suggesting lack of positive selection.