Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial – BCPP/Ya Tsie trial

Abstract

Background: Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence.Methods: To elucidate patterns of HIV spread in universal test-and-treat trials we quantified the contribution of geographic-location, gender, age and randomized-HIV-intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana. We sequenced HIV viral whole genomes from 5,114 trial participants among the 30 trial communities.Results: Deep-sequence phylogenetic analysis revealed that most inferred HIV transmissions within the trial occurred within the same or between neighboring communities, and between similarly-aged partners. Transmissions into intervention communities from control communities were more common than the reverse post-baseline (30% [12.2 - 56.7] versus 3% [0.1 - 27.3]) than at baseline (7% [1.5 - 25.3] versus 5% [0.9 - 22.9]) compatible with a benefit from treatment-as-prevention.Conclusion: Our findings suggest that population mobility patterns are fundamental to HIV transmission dynamics and to the impact of HIV control strategies.Funding: This study was supported by the National Institute of General Medical Sciences (U54GM088558); the Fogarty International Center (FIC) of the U.S. National Institutes of Health (D43 TW009610); and the President’s Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention (CDC) (Cooperative agreements U01 GH000447 and U2G GH001911).

Growing gender disparity in HIV infection in Africa: sources and policy implications

“…Empiric incidence data published over the last decade documents widespread declining incidence across the African continent 24 , and UNAIDS mathematic models from eastern and southern Africa have estimated a 43% reduction in incidence regionally since 2010 1 . Our findings are also compatible with genderstratified HIV incidence data from prospective African population-level studies that indicate greater differences in rates of new infections between men and women in the same cohort over calendar time 24 , data from population surveillance studies and HIV treatment and prevention trials showing lower levels of viral suppression among men compared to women with HIV 64,65 , and phylogenetic studies from Botswana 28 and Zambia 29 . Together, these observations suggest that the principal characteristics of the evolving HIV epidemic summarized in Table 1 likely apply more broadly in similar rural and semi-urban populations across Eastern and Southern Africa.…”

Population mobility and the development of Botswana’s generalized HIV epidemic: a network analysis

“…Botswana has recently achieved the 95-95-95 targets that UNAIDS specified needed to be reached by 2030 in order to eliminate HIV: 95% of people living with HIV to be diagnosed, 95% of the diagnosed to be on treatment, and 95% of those on treatment to be virally suppressed (Mine et al, 2022). However, transmission is continuing (Magosi et al, 2022), as is urbanization and large-scale population movements (Okano et al, 2021). The same processes that we have identified that may have contributed to the development of the generalized hyper-endemic HIV epidemic in Botswana may prevent the elimination of HIV.…”

“…A great deal is known about the epidemiology of HIV in Botswana in terms of the increase in prevalence and geographic variation in prevalence (Magosi et al, 2022; Novitsky et al, 2015; Novitsky et al, 2020; Okano et al, 2021). The first case of AIDS was reported in 1985 from the nickel mining town of Selebi Phikwe (African Natural Resources Center, 2016); in the late 1980s, additional cases were reported from two diamond mining towns (Jwaneng and Orapa) and the city, Francistown.…”

“…It found that, at that time, prevalence in the general population was ∼29% in women and ∼20% in men aged 15 to 49 years old. Notably, phylogenetic studies have shown that viral lineages have dispersed widely throughout Botswana suggesting large-scale population-level movements have occurred (Magosi et al, 2022; Novitsky et al, 2015; Novitsky et al, 2020).…”

Genomic population structures of microbial pathogens

“…Pybus summarized insights into the SARS-CoV-2 pandemic and other outbreaks from large scale phylogenetic analysis [ 18 ]; and Emma Hodcroft presented the CoVariants dashboard, which allows interactive exploration of SARS-COV-2 variants of concern. Finally, Christophe Fraser spoke about harnessing within- and between-host pathogen population genetics, using the approach implemented in P hyloscanner [ 19 ], to gain insights into the epidemiology, evolution and pathogenicity of diverse pathogens ranging from methicillin resistant Staphylococcus aureus (MRSA) [ 20 ] to SARS-COV-2 and HIV [ 21 ].…”