title: Phylodynamic analysis of HIV sub-epidemics in Mochudi, Botswana.
abstract: Southern Africa continues to be the epicenter of the HIV/AIDS epidemic. This HIV-1 subtype C epidemic has a predominantly heterosexual mode of virus transmission and high (>15%) HIV prevalence among adults. The epidemiological dynamics of the HIV-1C epidemic in southern Africa are still poorly understood. Here, we aim at a better understanding of HIV transmission dynamics by analyzing HIV-1 subtype C sequences from Mochudi, a peri-urban village in Botswana. HIV-1C env gene sequences (gp120 V1C5) were obtained through enhanced household-based HIV testing and counseling in Mochudi. More than 1200 sequences were generated and phylogenetically distinct sub-epidemics within Mochudi identified. The Bayesian birth-death skyline plot was used to estimate the effective reproductive number, R, and the timing of virus transmission, to classify sub-epidemics as "acute" (those with recent viral transmissions) or "historic" (those without recent viral transmissions). We identified two of the 15 sub-epidemics as "acute." The median estimates of R among the clusters ranged from 0.72 to 1.77. The majority of HIV lineages, 11 out of 15 clusters with 5+ members, appear to have been introduced to Mochudi between 1996 and 2002. The median peak duration of viral transmissions was 7.1 years (range 2.9-9.7 years). The median life span of identified HIV sub-epidemics, i.e., the time between the inferred epidemic origin and its most recent sample, was 13.1 years (range 10.2-22.1 years). Most viral transmissions within the sub-epidemics occurred between 1997 and 2007. The time period during which infected people are infectious appears to have decreased since the introduction of the national ART program in Botswana. Real-time HIV genotyping and breaking down local HIV epidemics into phylogenetically distinct sub-epidemics may help to reveal the structure and dynamics of HIV transmission networks in communities, and aid in the design of targeted interventions for members of the acute sub-epidemics that likely fuel local HIV/AIDS epidemics.
authors.affiliation: Harvard School of Public Health, Boston, MA, USA.
authors.forename: Vlad
authors.initials: V
authors.lastname: Novitsky
authors.affiliation: Institute of Integrative Biology, ETH Zürich, Zürich, Switzerland.
authors.forename: Denise
authors.initials: D
authors.lastname: Kühnert
authors.affiliation: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
authors.forename: Sikhulile
authors.initials: S
authors.lastname: Moyo
authors.affiliation: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
authors.forename: Erik
authors.initials: E
authors.lastname: Widenfelt
authors.affiliation: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
authors.forename: Lillian
authors.initials: L
authors.lastname: Okui
authors.affiliation: Harvard School of Public Health, Boston, MA, USA; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. Electronic address: messex@hsph.harvard.edu.
authors.forename: M
authors.initials: M
authors.lastname: Essex
mesh_terms: D000293:Adolescent; D000328:Adult; D001499:Bayes Theorem; D001902:Botswana / Q000453:epidemiology; D058872:Epidemics; D005260:Female; D015658:HIV Infections / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D010802:Phylogeny; D015995:Prevalence; D055815:Young Adult
keywords: Botswana; Effective reproductive number R; HIV sub-epidemics; HIV-1 subtype C; V1C5 sequences