Dynamics of viremia in primary HIV-1 infection in Africans: insights from analyses of host and viral correlates

Abstract

In HIV-1 infection, plasma viral load (VL) has dual implications for pathogenesis and public health. Based on well-known patterns of HIV-1 evolution and immune escape, we hypothesized that VL is an evolving quantitative trait that depends heavily on duration of infection (DOI), demographic features, human leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data from 421 African seroconverters with at least four eligible visits did show relatively steady VL beyond 3 months of untreated infection, but host and viral factors independently associated with cross-sectional and longitudinal VL often varied by analytical approaches and sliding time windows. Specifically, the effects of age, HLA-B(⁎)53 and infecting HIV-1 subtypes (A1, C and others) on VL were either sporadic or highly sensitive to time windows. These observations were strengthened by the addition of 111 seroconverters with 2-3 eligible VL results, suggesting that DOI should be a critical parameter in epidemiological and clinical studies.

Keywords: Africa; HIV-1; HLA; Statistical models; Subtype; Viral load.

Figure 1. Contrasting dynamics of HIV-1 viremia in African seroconverters defined by host and viral genotypes

Prospective viral load measurements are compared between HLA-B*18-positive and HLA-B*18-negative subjects (top panel, 3,154 person-visits) and between two major HIV-1 subtypes, HIV-1C and HIV-1A (bottom panel, 2,306 person-visits). Thick and thin lines correspond to the expected mean (average) value and 95% confidence intervals for each stratum (see Table 3 for summary statistics based on mixed models). Arrows point to plasma viral load measurements that are <400 RNA copies/ml (transformed to 1.30 log₁₀).

Figure 2. Viremia in HIV-1 seroconverters stratified by geography and HLA-B*53

Prospective viral load measurements (3,154 person-visits) are compared between Eastern Africa (Kenya, Rwandan and Uganda) and Southern Africa (Zambia) (top panel) and between HLA-B*53-positive and negative subgroups (bottom panel). Thick and thin lines correspond to the expected average value and 95% confidence intervals for each stratum (overall unadjusted P = 0.056). Arrow points to plasma viral load measurements that are <400 RNA copies/ml (transformed to 1.30 log₁₀).