Although fishing communities (FCs) in Uganda are disproportionately affected by HIV-1 relative to the general population (GP), the transmission dynamics are not completely understood. We earlier found most HIV-1 transmissions to occur within FCs of Lake Victoria. Here, we test the hypothesis that HIV-1 transmission in FCs is isolated from networks in the GP. We used phylogeography to reconstruct the geospatial viral migration patterns in 8 FCs and 2 GP cohorts and a Bayesian phylogenetic inference in BEAST v1.8.4 to analyse the temporal dynamics of HIV-1 transmission. Subtype A1 (pol region) was most prevalent in the FCs (115, 45.1%) and GP (177, 50.4%). More recent HIV transmission pairs from FCs were found at a genetic distance (GD) <1.5% than in the GP (Fisher’s exact test, p = 0.001). The mean time depth for pairs was shorter in FCs (5 months) than in the GP (4 years). Phylogeographic analysis showed strong support for viral migration from the GP to FCs without evidence of substantial viral dissemination to the GP. This suggests that FCs are a sink for, not a source of, virus strains from the GP. Targeted interventions in FCs should be extended to include the neighbouring GP for effective epidemic control.

ObjectivesWe assessed the prevalence and risk factors associated with virological failure among female sex workers living with HIV on antiretroviral therapy (ART) in Kampala, Uganda.MethodsWe conducted a cross-sectional study between January 2015 and December 2016 using routinely collected data at a research clinic providing services to women at high risk of STIs including HIV. Plasma samples were tested for viral load from HIV-seropositive women aged ≥18 years who had been on ART for at least 6 months and had received adherence counselling. Samples from women with virological failure (≥1000 copies/mL) were tested for HIV drug resistance by population-based sequencing. We used logistic regression to identify factors associated with virological failure.ResultsOf 584 women, 432 (74%) with a mean age of 32 (SD 6.5) were assessed, and 38 (9%) were found to have virological failure. HIV resistance testing was available for 78% (28/38), of whom 82.1% (23/28) had at least one major drug resistance mutation (DRM), most frequently M184V (70%, 16/23) and K103N (65%, 15/23). In multivariable analysis, virological failure was associated with participant age 18–24 (adjusted OR (aOR)=5.3, 95% CI 1.6 to 17.9), self-reported ART non-adherence (aOR=2.6, 95% CI 1.2 to 5.8) and baseline CD4+ T-cell count ≤350 cells/mm3 (aOR=3.1, 95% CI 1.4 to 7.0).ConclusionsA relatively low prevalence of virological failure but high rate of DRM was found in this population at high risk of transmission. Younger age, self-reported ART non-adherence and low CD4+ T-cell count on ART initiation were associated with increased risk of virological failure.

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.

The prevalence of transmitted drug resistance was lower than recently reported by the WHO. With 92% of all patients virologically suppressed on ART, the prevalence of virological failure was low when a cutoff of 1000 copies per milliliter is applied, and is in line with the third of the 90-90-90 UNAIDS targets. However, most failing patients had developed multiclass drug resistance.

To investigate the prevalence of transmitted drug resistance (TDR) among individuals with recent HIV-1 infection between February 2004 and January 2010 in a rural clinical cohort, samples from 72 participants were analyzed. Results from the 72 participants showed no protease inhibitor and nucleoside reverse transcriptase inhibitor-associated mutations. One participant (1.4%, 95% CI: 0.04-7.5%) had two nonnucleoside reverse transcriptase inhibitor mutations (G190E and P225H). HIV-1 subtype frequencies were A 22 (30.6%), D 38 (52.8%), and C 1 (1.4%); 11 (15.3%) were A/D unique recombinant forms. Seven years after the scale up of antiretroviral therapy (ART) in a rural clinical cohort in Uganda, the prevalence of TDR among recently HIV-1-infected individuals was low at 1.4%. Since our findings from an HIV study cohort may not be generalizable to the general population, routine TDR surveys in specific populations may be necessary to inform policy on the magnitude and prevention strategies of TDR.