Background:  HIV-1 from genital secretions and plasma may infect infants during gestation or delivery. HIV-1 replication and shedding in genital secretions and plasma may differ with respect to drug resistance, immune escape mutation(s), and envelope tropism. We compared genital secretions (cervical swab) viruses and plasma consensus pol sequences among 43 antiretroviral-naïve women, and diversity of env by clonal analysis of genital secretions and plasma virus among 6 women who transmitted HIV-1 to their infants

Methods:  HIV RNA was measured in cervical swab supernatant with a modified Roche Amplicor v1.5 assay. An optimal evolutionary model was identified using ModelTest, and the general time reversible model used to determine genetic distances (PAUP). Syn-SCAN (hivdb.stanford.edu) was used to determine evolutionary selection pressure. To quantify compartmental diversity and tropism, 20 env sequences were obtained by TA cloning from plasma and genital secretions virus from 6 transmitting mothers. Env tropism was estimated by a subtype C specific X4 algorithm.

Results:  There were 43 women with a median (IQR) of 310 (196 to 532.5) CD4⁺ cells/mm³, a mean of 4.24 (3.52 to 4.8) log₁₀ copies/mL HIV-1 RNA in plasma and 3.55 (3.06 to 4.09) log₁₀ copies/mL in genital secretions were studied. Plasma–genital secretions evolution in pol were marginally greater among the 7 transmitting women compared to 36 non-transmitters (p = 0.08). Cervical and plasma pol sequences differed frequently at RT positions 36 (23%), 123 (23%), and 211 (19%) without evidence of drug resistance. Sequencing clones from 6 transmitting women from plasma and genital secretions demonstrated evidence of distinct X4 tropic clones; 2 women had a mix of R5 and X4-tropic env clones in both plasma and genital secretions, 3 had only R5 viruses and 1 (with >500 CD4 cells/mm³) had X4-tropic env in genital secretions and plasma. Phylogenetic analysis demonstrated compartmental clades among the 3 women with R5 viruses and mixtures of plasma and genital secretions viruses in women with X4-tropic viruses.  

Conclusions:  Among subtype C HIV-1-infected pregnant women, selection of viruses in genital secretions relative to plasma in both pol and env genes, provide evidence for independent compartmental replication in genital secretions with a continuum of selection for CTL epitope evolution (immune escape) and viral tropism in each compartment. Frequent identification of X4-tropism in genital secretions and plasma of women who transmitted HIV suggests that further studies of tropism of genital secretions viruses are warranted as R5 inhibitors are developed for pre and post-exposure prevention.