Demographics of sources of HIV-1 transmission in Zambia: a molecular epidemiology analysis in the HPTN 071 PopART study

Matthew Hall; Tanya Golubchik; David Bonsall; Lucie Abeler-Dörner; Mohammed Limbada; Barry Kosloff; Ab Schaap; Mariateresa de Cesare; George MacIntyre-Cockett; Newton Otecko; William Probert; Oliver Ratmann; Ana Bulas Cruz; Estelle Piwowar-Manning; David N Burns; Myron S Cohen; Deborah J Donnell; Susan H Eshleman; Musonda Simwinga; Sarah Fidler; Richard Hayes; Helen Ayles; Christophe Fraser; HPTN 071 (PopART) Phylogenetics protocol team; PANGEA consortium

doi:10.1016/S2666-5247(23)00220-3

Demographics of sources of HIV-1 transmission in Zambia: a molecular epidemiology analysis in the HPTN 071 PopART study

Lancet Microbe. 2024 Jan;5(1):e62-e71. doi: 10.1016/S2666-5247(23)00220-3. Epub 2023 Dec 8.

Authors

Matthew Hall¹, Tanya Golubchik², David Bonsall³, Lucie Abeler-Dörner¹, Mohammed Limbada⁴, Barry Kosloff⁵, Ab Schaap⁴, Mariateresa de Cesare³, George MacIntyre-Cockett³, Newton Otecko¹, William Probert¹, Oliver Ratmann⁶, Ana Bulas Cruz¹, Estelle Piwowar-Manning⁷, David N Burns⁸, Myron S Cohen⁹, Deborah J Donnell¹⁰, Susan H Eshleman⁷, Musonda Simwinga⁴, Sarah Fidler¹¹, Richard Hayes¹², Helen Ayles⁵, Christophe Fraser¹³; HPTN 071 (PopART) Phylogenetics protocol team; PANGEA consortium

Collaborators

Yaw Agyei, Nulda Beyers, Peter Bock, Virginia Bond, Justin Bwalya, Anne Cori, Anneen Deventer, Rory Dunbar, Wafaa El-Sadr, Lynda Emel, Sian Floyd, Sam Griffith, James Hargreaves, Katharina Hauck, Tanette Headen, Graeme Hoddinott, Anelet James, Karen Jennings, Sarah Kanema, Barry Kosloff, James Kruger, Ramya Kumar, David Macleod, Nozizwe Makola, Nomtha Mandla, Eric Miller, Ayana Moore, Lawrence Mwenge, Heather Noble, Mwelwa Phiri, Michael Pickles, Kalpana Sabapathy, Ephraim Sakala, Rafael Sauter, Kwame Shanaube, Andrew Silumesi, Nirupama Sista, Tim Skalland, Peter Smith, Ranjeeta Thomas, Sten Vermund, Rhonda White, Ethan Wilson, Blia Yang, Krista Yuhas, Rory Bowden, Vincent Calvez, Max Essex, Kate Grabowski, Ravindra Gupta, Joshua Herbeck, Joseph Kagaayi, Pontiano Kaleebu, Jairam Lingappa, Sikhulile Moyo, Vladimir Novitsky, Thumbi Ndung'u, Deenan Pillay, Thomas Quinn, Andrew Rambaut, Janet Seeley, Deogratius Ssemwanga, Frank Tanser, Maria Wawer

Affiliations

¹ Pandemic Sciences Institute and Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
² Pandemic Sciences Institute and Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Sydney Infectious Diseases Institute, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
³ Pandemic Sciences Institute and Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁴ Zambart, University of Zambia, Lusaka, Zambia.
⁵ Zambart, University of Zambia, Lusaka, Zambia; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.
⁶ Department of Mathematics, Imperial College London, London, UK.
⁷ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
⁹ Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁰ Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹¹ Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
¹² Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
¹³ Pandemic Sciences Institute and Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. Electronic address: christophe.fraser@bdi.ox.ac.uk.

Abstract

Background: In the last decade, universally available antiretroviral therapy (ART) has led to greatly improved health and survival of people living with HIV in sub-Saharan Africa, but new infections continue to appear. The design of effective prevention strategies requires the demographic characterisation of individuals acting as sources of infection, which is the aim of this study.

Methods: Between 2014 and 2018, the HPTN 071 PopART study was conducted to quantify the public health benefits of ART. Viral samples from 7124 study participants in Zambia were deep-sequenced as part of HPTN 071-02 PopART Phylogenetics, an ancillary study. We used these sequences to identify likely transmission pairs. After demographic weighting of the recipients in these pairs to match the overall HIV-positive population, we analysed the demographic characteristics of the sources to better understand transmission in the general population.

Findings: We identified a total of 300 likely transmission pairs. 178 (59·4%) were male to female, with 130 (95% CI 110-150; 43·3%) from males aged 25-40 years. Overall, men transmitted 2·09-fold (2·06-2·29) more infections per capita than women, a ratio peaking at 5·87 (2·78-15·8) in the 35-39 years source age group. 40 (26-57; 13·2%) transmissions linked individuals from different communities in the trial. Of 288 sources with recorded information on drug resistance mutations, 52 (38-69; 18·1%) carried viruses resistant to first-line ART.

Interpretation: HIV-1 transmission in the HPTN 071 study communities comes from a wide range of age and sex groups, and there is no outsized contribution to new infections from importation or drug resistance mutations. Men aged 25-39 years, underserved by current treatment and prevention services, should be prioritised for HIV testing and ART.

Funding: National Institute of Allergy and Infectious Diseases, US President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation, National Institute on Drug Abuse, and National Institute of Mental Health.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult
Demography
Female
HIV Infections* / drug therapy
HIV Infections* / epidemiology
HIV Seropositivity*
HIV-1* / genetics
Humans
Male
Molecular Epidemiology
United States
Zambia / epidemiology

Abstract

Publication types

MeSH terms

Grants and funding