HIV-1 Subtype Distribution Trends and Evidence of Transmission Clusters Among Incident Cases in a Rural Clinical Cohort in Southwest Uganda, 2004–2010

Abstract

The high diversity of HIV-1 has been shown to affect disease progression, transmission, and response to antiretroviral therapy and may influence HIV vaccine design. We describe the distribution trends of HIV-1 subtypes over a 7-year period among incident cases in a rural clinical cohort in Southwest Uganda and identify transmission clusters. Viral RNA was extracted from cryopreserved plasma samples from 94 participants who seroconverted and enrolled between 2004 and 2010. Partial gag (p24) and env (gp41) genes were directly sequenced to identify subtypes and transmission clusters with more than 95% bootstrap values. Direct sequencing of the partial pol gene and use of individual participant sexual life histories were also used to confirm these transmission clusters. The overall gag/env subtype distribution was A 28% (n=26), C 1% (n=1), and D 45% (n=42) and 27% (n=25) were intergene unique recombinant forms. The proportions of subtype A, D, or recombinants showed no significant increasing or decreasing trend over this time period (p=0.51). Phylogenetic analysis of the three genes confirmed 13 transmission clusters of which seven clusters were confirmed sexual partners using individual participants' sexual life histories. Subtype D has remained the predominant subtype in this population. From 2004 to 2010, there was no change in the proportions of these subtypes. Phylogenetic analysis and participants' sexual life histories revealed several transmission clusters. The high proportion of transmission clusters observed suggests continued high-risk sexual behavior and mixing in some individuals and possibly super transmitters in this presumed low-risk cohort, but also indicates that many transmissions occur in early HIV infection. This calls for early and targeted effective prevention and treatment intervention in this population.

HIV-1 transmission networks in high risk fishing communities on the shores of Lake Victoria in Uganda: A phylogenetic and epidemiological approach

“…Among HIV incident cases, the Rakai study estimated clustering within households at 39%, similar to our study [17]. Another study in Uganda (albeit a low risk population) showed that 27% sequences from incident cases in the gag and env gene regions were clustered suggesting a substantial risk of transmission in early infections in this population [18]. Findings from Rakai in Uganda [34], and a Canadian study [32] showed that some new infections could be due to sexual contacts with recently infected individuals.…”

“…Combining phylogenetics and epidemiological data our study revealed 24% of individuals with sequences from the gag / env gene regions formed 34 transmission clusters. The level of clustering detected is within the 5–50% range previously estimated from several studies [16–18, 32]. …”

“…New approaches combining phylogenetic with epidemiological data have advanced our knowledge of sexual networks, and combined with statistical methods may provide insights into underlying risk factors for local HIV epidemics [14, 15]. Few studies incorporating phylogenetics have been conducted among populations with predominant HIV A/D subtype infections, which occur mainly in East Africa to understand complex HIV transmission dynamics at a population level [16–18]. A thorough understanding of drivers of individual epidemics is required to develop, implement and maintain effective HIV prevention programmes [15, 19, 20].…”

Concentrated HIV subepidemics in generalized epidemic settings

“…71 In the same country, another study suggested that the presence of super transmitters in early HIV infection contributed a disproportionate number of transmissions in a low-risk rural cohort. 72 These kinds of studies are currently being expanded to other large demographic sites in generalized epidemics in Africa, for example the Mochudi treatment as prevention (TasP) trial in Botswana and TasP trial at the Africa Centre in rural South Africa, 73 which has started to produce large molecular epidemiology datasets.…”

Impaired natural killer cell responses are associated with loss of the highly activated NKG2A+CD57+CD56dim subset in HIV-1 subtype D infection in Uganda

“…The Ugandan HIV-1 epidemic, with a prevalence of 7.3% [1], is predominantly composed of subtype A, D and recombinant viruses [2,3]. HIV-1 subtype affects the rate of disease progression [4], yet it is not clear why.…”