Infection with Multiple Human Immunodeficiency Virus Type 1 Variants Is Associated with Faster Disease Progression

Abstract

Human immunodeficiency virus type 1 (HIV-1)-infected individuals develop a genetically diverse virus population over time, but often only a limited number of viral variants are transmitted from a chronic carrier to a newly infected person. Interestingly, many women but few men are infected by multiple HIV-1 variants from a single partner. To determine whether the complexity of the infecting virus population influences clinical outcome, we examined viral diversity in the HIV-1 envelope sequences present at primary infection in 156 women from Kenya for whom we had follow-up data on viral RNA levels and CD4 T-cell counts. Eighty-nine women had multiple viral genotypes, while 67 women had a single genotype at primary infection. Women who acquired multiple viral genotypes had a significantly higher viral load (median, 4.84 versus 4.64 log 10 copies/ ml, P ‫؍‬ 0.04) and a significantly lower CD4؉ -T-cell count (median, 416 versus 617 cells/mm 3 , P ‫؍‬ 0.01) 4 to 24 months after infection compared to women who were infected with a single viral genotype. These studies suggest that early HIV-1 genetic diversity is linked to faster disease progression.

Human Immunodeficiency Virus Type 1 V1-to-V5 Envelope Variants from the Chronic Phase of Infection Use CCR5 and Fuse More Efficiently than Those from Early after Infection

“…The median interval of time for the analyzed sequences was about 35 months (range, 18 to 46 months). In previous studies, we have shown that five (QA284, QA779, QB670, QC168, and QC449) of the nine subjects examined in this study had strictly homogenous envelope sequences early in infection (74,75). Thus, for these subjects, only one early-infection V1-V5 sequence was isolated, and for the remaining four subjects, multiple sequences (median, 3; range, 3 to 4) were isolated from early in infection (Table 1).…”

Recombination-mediated escape from primary CD8+ T cells in acute HIV-1 infection

“…Infection with multiple T/F viruses is linked to factors that are known to increase overall transmission rates, such as higher risk sex acts and other concurrent sexually transmitted infections [12,[15][16][17][18][19]. Several studies have associated infection with multiple HIV-1 T/F viruses, multiple subtypes, and/or a diverse virus population, with higher pVL setpoint, faster CD4+ T cell decline, earlier need for anti-retroviral therapy and a worse prognosis for the infected individual [14,[20][21][22][23][24].…”

Association between Latent Proviral Characteristics and Immune Activation in Antiretrovirus-Treated Human Immunodeficiency Virus Type 1-Infected Adults

“…For example, individuals initially infected with a more diverse viral population undergo more rapid HIV-1 disease progression (23,24). However, it is unclear whether these viral characteristics drive poor health outcomes by influencing levels of immune activation.…”

“…Viral characteristics such as the presence of drug resistance mutations, coreceptor tropism, and the diversity of the proviral population are associated with HIV-1 disease progression (23)(24)(25)(26)(27). For example, individuals initially infected with a more diverse viral population undergo more rapid HIV-1 disease progression (23,24).…”