Infecting HIV-1 Subtype Predicts Disease Progression in Women of Sub-Saharan Africa

Abstract

IntroductionLong-term natural history cohorts of HIV-1 in the absence of treatment provide the best measure of virulence by different viral subtypes.MethodsNewly HIV infected Ugandan and Zimbabwean women (N = 303) were recruited and monitored for clinical, social, behavioral, immunological and viral parameters for 3 to 9.5 years.ResultsUgandan and Zimbabwean women infected with HIV-1 subtype C had 2.5-fold slower rates of CD4 T-cell declines and higher frequencies of long-term non-progression than those infected with subtype A or D (GEE model, P < 0.001), a difference not associated with any other clinical parameters. Relative replicative fitness and entry efficiency of HIV-1 variants directly correlated with virulence in the patients, subtype D > A > C (P < 0.001, ANOVA).DiscussionHIV-1 subtype C was less virulent than either A or D in humans; the latter being the most virulent. Longer periods of asymptomatic HIV-1 subtype C could explain the continued expansion and dominance of subtype C in the global epidemic.

Nef-mediated inhibition of NFAT following TCR stimulation differs between HIV-1 subtypes

“…There are conflicting reports of the rate of disease progression of subtype C relative to other M group subtypes (Ariën et al, 2007;Easterbrook et al, 2010;Neilson et al, 1999;Silveira et al, 2012;Vasan et al, 2006). However, a recent study controlling for clinical factors showed that subtype C infection was associated with slower rate of CD4 decline relative to subtype A or D infection (Venner et al, 2016). Subtypes A and C are the most prevalent subtypes (Buonaguro et al, 2007;Hemelaar, 2012;Tebit and Arts, 2011) which may also be expanding more rapidly than other subtypes, as evidenced by expansion of subtype C in Brazil, India and sub-Saharan Africa (Gräf and Pinto, 2013;Rodriguez et al, 2009;Venner et al, 2016) and increased prevalence of subtype A in Uganda (Conroy et al, 2010).…”

“…However, a recent study controlling for clinical factors showed that subtype C infection was associated with slower rate of CD4 decline relative to subtype A or D infection (Venner et al, 2016). Subtypes A and C are the most prevalent subtypes (Buonaguro et al, 2007;Hemelaar, 2012;Tebit and Arts, 2011) which may also be expanding more rapidly than other subtypes, as evidenced by expansion of subtype C in Brazil, India and sub-Saharan Africa (Gräf and Pinto, 2013;Rodriguez et al, 2009;Venner et al, 2016) and increased prevalence of subtype A in Uganda (Conroy et al, 2010). Overall, the most attenuated subtypes -A and Cwhich were the least functional in the present study of Nef function, display slower disease progression yet are the most prevalent and are expanding rapidly.…”

“…Overall, the most attenuated subtypes -A and Cwhich were the least functional in the present study of Nef function, display slower disease progression yet are the most prevalent and are expanding rapidly. The increased dominance of subtypes A and C may be due to longer asymptomatic periods (Venner et al, 2016) and/or the low replication capacity of these subtypes may favour transmission due to increased half-life of infected cells in genital fluids, although this hypothesis still requires experimental verification Fig. 5.…”

Specialized DNA structures act as genomic beacons for integration by evolutionarily diverse retroviruses

“…Details pertaining to the Uganda study population have been reported previously ( 46 – 49 ). Briefly, women who became HIV infected while participating in the Hormonal Contraception and Risk of HIV Acquisition Study in Uganda were enrolled upon primary infection with HIV-1 into a subsequent study, the Hormonal Contraception and HIV-1 Genital Shedding and Disease Progression among Women with Primary HIV Infection (GS) Study.…”

Why Are Some HIV-1 Subtypes More “Wimpy” at Causing Disease?

“…In this issue of EBioMedicine , Venner and co-authors [1] expand the observation that variant subtypes of HIV-1 are highly divergent in terms of biological phenotypes. This study goes further to link this diversity to disease course and outcome.…”