Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis

Abstract

The natural course of HIV-1 infection is characterized by a high degree of heterogeneity in viral load, not just within patients over time, but also between patients, especially during the asymptomatic stage of infection. Asymptomatic, or set-point, viral load has been shown to correlate with both decreased time to AIDS and increased infectiousness. The aim of this study is to characterize the epidemiological impact of heterogeneity in set-point viral load. By analyzing two cohorts of untreated patients, we quantify the relationships between both viral load and infectiousness and the duration of the asymptomatic infectious period. We find that, because both the duration of infection and infectiousness determine the opportunities for the virus to be transmitted, this suggests a trade-off between these contributions to the overall transmission potential. Some public health implications of variation in set-point viral load are discussed. We observe that set-point viral loads are clustered around those that maximize the transmission potential, and this leads us to hypothesize that HIV-1 could have evolved to optimize its transmissibility, a form of adaptation to the human host population. We discuss how this evolutionary hypothesis can be tested, review the evidence available to date, and highlight directions for future research.cohort studies ͉ life-history ͉ mathematical model ͉ trade-off ͉ virulence

Phylogenetically resolving epidemiologic linkage

“…The number of lineages with A or B labels that merge in the source population is therefore a random variable determined by the sample size, sampling time, and within-host dynamics. In general, this quantity will be smaller than the HIV-1 within-host population size (35)(36)(37), or effective population size (38)(39)(40), and consequently sampling plays an important role in the ability of genetic data to resolve an epidemiologic linkage. Furthermore, first principles predict that as the time between transmission and sampling increases, eventually old lineages will be lost in the derived populations, leading to loss of the paraphyletic signal (Fig.…”

Crossing the scale from within-host infection dynamics to between-host transmission fitness: a discussion of current assumptions and knowledge

“…Possibly, one of the best studied pathogens in this regard is HIV. Data for HIV correlating the viral load in serum with probability of infection in a partner suggest a sigmoid relationship (figure 2; [42][43][44]). However, higher viral load also leads to more rapid progression to the terminal AIDS stage [43,45], therefore reducing the time during which transmission can occur (figure 2).…”

From within-host interactions to epidemiological competition: a general model for multiple infections

“…However, earlier models have shown that further assumptions would then be needed because if both virulence and transmission rates are linear functions of parasite load, natural selection will always favour the strains with the highest possible level of virulence [51]. One possibility could be to focus on a biological system where these relationships have been parametrized, such as HIV in humans [52], myxomatosis in rabbits [53], Ophryocystis elektroscirrha in monarch butterflies [54] or the cauliflower mosaic virus in turnips [55].…”