HIV transmission dynamics: Infectivity, sexual partnership patterns, and the role of early infection

Although remarkable progress has been made in the diagnosis, treatment, and prevention of HIV, a cure is unavailable and many of the most promising prevention interventions have failed. At this critical juncture in the epidemic, there is a necessity for improved understanding of the fundamental drivers of the epidemic, as well as an urgent need for innovative interventions against HIV. This dissertation focuses on two of these fundamental drivers - the heterosexual infectivity of HIV-1 and the details of sexual partnership patterns - as well as the power of interventions initiated during the highly infectious period of early HIV infection (EHI). We conducted a systematic review and meta-analysis of the heterosexual infectivity of HIV-1, defined as the per-contact probability of HIV-1 transmission in a single heterosexual contact between an infected and a susceptible individual. Infectivity estimates were extremely heterogeneous, ranging from zero transmissions after more than 100 penile-vaginal contacts in some sero-discordant couples to one transmission for every 3.1 episodes of heterosexual anal intercourse. Several co-factors were associated with increased infectivity. Infectivity differences (95% confidence intervals), expressed as number of transmissions per 1000 contacts, were 8 (0-16) comparing uncircumcised to circumcised male susceptibles, 6 (3-9) comparing susceptible individuals with and without GUD, 2 (1-3) comparing late-stage to mid-stage index cases, and 3 (0-5) comparing early-stage to mid-stage index cases. We also analyzed recent sexual partnership patterns in a sexually transmitted infections (STI) clinic in Lilongwe, Malawi. We found that multiple sexual partnerships were uncommon (14%), and partnerships were long on average (mean=858 days). Among those reporting multiple recent partners, patterns ranged from long-term concurrency (mean overlap=246 days) to narrowly spaced consecutive partnerships (mean gap=21 days), presenting a substantial risk for efficient HIV transmission. Finally, we conducted a mathematical modeling study to determine the contribution of EHI to epidemic spread in Lilongwe, Malawi. Our analyses suggest that 38.4% (95% CI: 18.6%-57.5%) of ongoing HIV transmissions in Lilongwe can be attributed to EHI index cases, and that interventions targeting the entire duration of infection will be needed to have a significant, lasting effect on the epidemic.