Disentangling the impact of within-host evolution and transmission dynamics on the tempo of HIV-1 evolution

Abstract

Background Although evidence exists for a selective component at transmission, it is clear that HIV-1 transmission is also to a large extent driven by drift. The variation in inoculum size among different risk groups therefore implies that the adaptation rate of HIV may vary between epidemics with different risk group compositions. Furthermore, factors that govern the rate of within-host evolution may also vary by risk group and therefore contribute to evolutionary differences at the epidemic level. Methods We adopted a population genetic approach to test whether the different proportions of multi-variant transmissions are reflected by varying proportions of transmitted diversity between men-having-sex-with-men (MSM), heterosexual (HET) and direct blood contact (BC) sub-populations. To this purpose, we collected all available transmission chain clonal sequence data sets (n = 70) available at the Los Alamos HIV website and through an extensive literature search. To assess evolutionary rate differences among different risk groups, we compiled risk group datasets for several subtypes and directly compared the absolute substitution rate and its synonymous and non-synonymous components. Results There was sufficient demographic signal to inform the transmission model in BEAST using env data to compare the transmission bottleneck size between the MSM and HET risk groups, i.e. the largest contributors to HIV spread. We find no indications for a different proportion of transmitted genetic diversity at the population level between these groups. In the direct rate comparisons between risk groups, however, we consistently recover a higher evolutionary rate in the male dominated risk group compared to the HET datasets. Conclusions We find that the risk group composition impacts the viral evolutionary rate and therefore potentially also the adaptation rate. In particular, risk group-specific sex ratios, and the variation in within-host evolutionary rates between males and females, imposes evolutionary rate differences at the epidemic level, but we cannot exclude a role of varying transmission rates.

Patterns and rates of viral evolution in HIV-1 subtype B infected females and males

“…Recent studies have investigated transmission dynamics and within-host virus evolution to explain risk group-associated ( i . e ., MSM, HET, or IDU) differences in HIV-1 evolution at the population level [ 18 , 23 , 111 ], as this may help to inform treatment and prevention strategies within certain demographics. For instance, Vrancken et al .…”

“…Vrancken et al . reported that evolutionary rates were lowest in heterosexual (HET) compared to MSM and intravenous drug users (IDU) [ 23 ], and the authors suggested that gender ratios within a given risk group may explain the associated evolutionary rate differences. Specifically, the incidence of multi-variant transmission is reported to be 2-fold higher in MSM [ 24 ] than in HET risk groups [ 7 , 25 , 26 ].…”

Phylodynamic and Phylogeographic Profiles of Subtype B HIV-1 Epidemics in South Spain

“…This rate tended to be higher for the lineages formed largely by MSMs and IVDUs, which suggests greater transmission efficiency and faster subtype B evolution in the groups at risk of HIV-1 infection [41]. …”

Size, Composition, and Evolution of HIV DNA Populations during Early Antiretroviral Therapy and Intensification with Maraviroc

“…To further assess the presence of viral evolution, we applied a Bayesian approach to our heterochronous data set. While these techniques have been used to estimate the evolutionary rate of HIV RNA populations (43,44), little is known about the efficacy of these methods to…”