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HIV-1 Genetic Diversity Higher in Vaginal Tract Than Blood

University of Western Ontario investigators have found that the genetic diversity of HIV-1 during early infection is greater in the vaginal tract than in the bloodstream.

University of Western Ontario investigators have conducted the first study to reveal that the HIV-1 variants found in the vaginal tract of recently infected women are more diverse than those found in blood. These findings may help guide the development of HIV vaccines and other infection prevention strategies.

Scientists have purported that when HIV-1 enters the vaginal tract, the population of the virus is genetically diverse; however, the population is then filtered as it penetrates and infects layers of the vagina to get into the bloodstream, resulting in a systemic infection with a single genetic HIV-1 variant in the blood.

To better understand this hypothesized “genetic bottleneck,” investigator, Katja Klein, PhD, and colleagues, “conducted the first study to compare HIV-1 genetic diversity between the vaginal tract and the blood in newly infected people,” according to a press release on the research.

For the study, samples of blood plasma (n = 67) and vaginal tract (n = 23) of 72 HIV-1-infected women from Uganda and Zimbabwe were analyzed using next-generation deep sequencing. The women were enrolled into a study entitled, “Hormonal Contraception and HIV-1 Genital Shedding and Disease Progression among Women with Primary HIV Infection (GS) Study” after they had been diagnosed with HIV-1 infection while they were already participating in the “Hormonal Contraception and Risk of HIV Acquisition Study.” The samples had been collected within 7 months of infection.

According to the study, “viral load assessment revealed a significantly (P<0.001) lower mean viral load of 5,057 RNA copies/ml in cervical samples compared to mean viral load of 112,733 RNA copies/ml in plasma samples at the time point of sample collection (0—7 months).”

After comparing the genetic diversity of the samples from the vaginal track with those from blood plasma, the investigators found a mean range of 5.7 genetic variants in the vaginal samples, while the blood plasma sample yielded a mean of 1.7 variants. The authors write that “HIV genetic diversity was calculated based on all sequence reads in the patient sample population rather than just unique reads.”

These findings were, “independent of HIV-1 subtype, hormonal contraceptive use, or the number of sex acts and partners,” the authors write.

Although the authors acknowledge that “genetic diversity in the vaginal tract may have arisen post-infection,” they feel that this is not likely as they would have seen a similar range of diversity in the bloodstream.

The authors put forth that their findings “provide novel in vivo evidence for the existence of an intra-patient genetic bottleneck restricting the HIV-1 from the vaginal tract to the blood during early heterosexual HIV-1 transmission.” They add that “Identifying and characterizing the diversity of HIV-1 in the donor and recipient compartments involved in transmission may provide better applications of HIV-1 preventative therapies. These studies will allow to more accurately and efficaciously target the virus at the most susceptible states. Furthermore, the existence of multiple viral clones with increased diversity in the mucosa will have a significant impact on the design of treatment and eradication/cure strategies.”