Diversity, Divergence, and Evolution of Cell-Free Human Immunodeficiency Virus Type 1 in Vaginal Secretions and Blood of Chronically Infected Women: Associations with Immune Status

Abstract

Most human immunodeficiency virus type 1 (HIV-1) infections are believed to be the result of exposure to the virus in genital secretions. However, prevention and therapeutic strategies are usually based on characterizations of HIV-1 in blood. To understand better the dynamics between HIV-1 quasispecies in the genital tract and blood, we performed heteroduplex assays on amplified env products from cell-free viral RNA in paired vaginal secretion (VS) and blood plasma (BP) samples of 14 women followed for 1.5 to 3.5 years. Diversity and divergence were less in VS than in BP (P ‫؍‬ 0.03 and P < 0.01, respectively), and divergence at both sites was correlated with blood CD4 ؉ cell levels (VS, P ‫؍‬ 0.05; BP, P ‫؍‬ 0.01). Evolution of quasispecies was observed in 58% of the women; the loss or gain of quasispecies in VS or BP was always accompanied by such changes at the other site. In addition, sustained compartmentalization of quasispecies in VS was found for four women, even as CD4 ؉ cell levels decreased to low levels (<50 cells/l). Quasispecies changes over time were associated with fluctuations in CD4 ؉ cell levels; concordant increases or decreases in VS and BP divergence had greater CD4 ؉ cell level changes than intervals with discordant changes (P ‫؍‬ 0.05), and women with evolving quasispecies had greater decreases in CD4؉ cell levels compared to that for women who maintained the same quasispecies (P < 0.05). Thus, diversity, divergence, and evolution of cell-free HIV-1 in VS can be different from that in BP, and dynamics between their respective quasispecies are associated with changes in CD4 ؉ cell levels.

Genetic and Phenotypic Features of Blood and Genital Viral Populations of Clinically Asymptomatic and Antiretroviral-Treatment-Naive Clade A Human Immunodeficiency Virus Type 1-Infected Women

“…In the four selected women, the viral genetic diversity between the blood and the genital tract appeared to be significantly different, which was highly suggestive of a compartmentalized genetic evolution of the variant populations between the female genital tract and the systemic compartments at the time of the chronic phase of HIV-1 infection (Table 2). Taken together, these findings supported the hypothesis that the female genital tract is an independent viral anatomic compartment that could harbor genetic variant populations that are distinctly different from those found in the peripheral blood of women recently infected or at the chronic phase of HIV-1 infection (3,4,6,12,15).…”

“…Several genetic studies have predicted viral tropism in the female genital tract (4,6) and have suggested that women infected by subtype B virus may harbor distinct CCR5-tropic or CXCR4-tropic viral populations between blood and the genital tract, whereas those infected with other HIV subtypes do not (4,6). In a recent report, in which coreceptor usage was determined using a cell-cell fusion assay, R5-tropic variants were found in both systemic and genital compartments of five clade B HIV-1-infected women at the early stage of the disease (15). The usage of coreceptor CCR5 or CXCR4 by infectious variants present in the female genital tract are likely important determinants implicated in the mechanisms of heterosexual transmission from female to male (3).…”

Comparative Study of Methods for Detecting Sequence Compartmentalization in Human Immunodeficiency Virus Type 1

“…HIV type 1 (HIV-1) populations isolated from the genital tract in both men and women have been reported as compartmentalized (12,29,43,45,47,48,65,73) when compared to the viruses isolated from the blood or lymphoid tissue. Since the most common route of HIV transmission worldwide is genital exposure (52), the study of HIV populations replicating in the genital tract will help us develop strategies to prevent transmission.…”

Carga viral vaginal de HIV em mulheres brasileiras infectadas pelo HIV

“…Se tivéssemos utilizado o mesmo valor, em lugar de 50 cópias/mL, teriam sido identificados mais três casos. Também se sabe que a diversidade e evolução das cepas do HIV livre vaginal diferem daquelas encontradas no plasma, o que se associa aos níveis de linfócitos CD4 16 . O comportamento diferenciado do HIV no sangue e no meio cérvico-vaginal são aspectos da compartimentalização não estudados nesta casuística.…”