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

Background Fishing communities around Lake Victoria in sub-Saharan Africa have been characterised as a population at high risk of HIV-infection. Methods Using data from a cohort of HIV-positive individuals aged 13–49 years, enrolled from 5 fishing communities on Lake Victoria between 2009–2011, we sought to identify factors contributing to the epidemic and to understand the underlying structure of HIV transmission networks. Clinical and socio-demographic data were combined with HIV-1 phylogenetic analyses. HIV-1 gag-p24 and env-gp-41 sub-genomic fragments were amplified and sequenced from 283 HIV-1-infected participants. Phylogenetic clusters with ≥2 highly related sequences were defined as transmission clusters. Logistic regression models were used to determine factors associated with clustering. Results Altogether, 24% (n = 67/283) of HIV positive individuals with sequences fell within 34 phylogenetically distinct clusters in at least one gene region (either gag or env). Of these, 83% occurred either within households or within community; 8/34 (24%) occurred within household partnerships, and 20/34 (59%) within community. 7/12 couples (58%) within households clustered together. Individuals in clusters with potential recent transmission (11/34) were more likely to be younger 71% (15/21) versus 46% (21/46) in un-clustered individuals and had recently become resident in the community 67% (14/21) vs 48% (22/46). Four of 11 (36%) potential transmission clusters included incident-incident transmissions. Independently, clustering was less likely in HIV subtype D (adjusted Odds Ratio, aOR = 0.51 [95% CI 0.26–1.00]) than A and more likely in those living with an HIV-infected individual in the household (aOR = 6.30 [95% CI 3.40–11.68]). Conclusions A large proportion of HIV sexual transmissions occur within house-holds and within communities even in this key mobile population. The findings suggest localized HIV transmissions and hence a potential benefit for the test and treat approach even at a community level, coupled with intensified HIV counselling to identify early infections.

[1]  A. Smolak A meta-analysis and systematic review of HIV risk behavior among fishermen , 2014, AIDS care.

[2]  Rui Wang,et al.  Linkage of Viral Sequences among HIV-Infected Village Residents in Botswana: Estimation of Linkage Rates in the Presence of Missing Data , 2014, PLoS Comput. Biol..

[3]  A. Kamali,et al.  HIV and syphilis prevalence and associated risk factors among fishing communities of Lake Victoria, Uganda , 2011, Sexually Transmitted Infections.

[4]  Rodrigo Lopez,et al.  Clustal W and Clustal X version 2.0 , 2007, Bioinform..

[5]  P. Harrigan,et al.  The impact of clinical, demographic and risk factors on rates of HIV transmission: a population-based phylogenetic analysis in British Columbia, Canada. , 2015, The Journal of infectious diseases.

[6]  David C. Nickle,et al.  ViroBLAST: a stand-alone BLAST web server for flexible queries of multiple databases and user's datasets , 2007, Bioinform..

[7]  David Dunn,et al.  Molecular Phylodynamics of the Heterosexual HIV Epidemic in the United Kingdom , 2009, PLoS pathogens.

[8]  J. Seeley,et al.  HIV type 1 subtype distribution, multiple infections, sexual networks, and partnership histories in female sex workers in Kampala, Uganda. , 2012, AIDS research and human retroviruses.

[9]  D. Gotte,et al.  Evolution and probable transmission of intersubtype recombinant human immunodeficiency virus type 1 in a Zambian couple , 1997, Journal of virology.

[10]  Katy Robinson,et al.  How the Dynamics and Structure of Sexual Contact Networks Shape Pathogen Phylogenies , 2013, PLoS Comput. Biol..

[11]  J. Felsenstein CONFIDENCE LIMITS ON PHYLOGENIES: AN APPROACH USING THE BOOTSTRAP , 1985, Evolution; international journal of organic evolution.

[12]  O. Laeyendecker,et al.  Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. , 2005, The Journal of infectious diseases.

[13]  D. Pillay,et al.  Understanding Drivers of Phylogenetic Clustering in Molecular Epidemiological Studies of HIV , 2014, The Journal of infectious diseases.

[14]  Ann M. Dennis,et al.  Phylogenetic Studies of Transmission Dynamics in Generalized HIV Epidemics: An Essential Tool Where the Burden is Greatest? , 2014, Journal of acquired immune deficiency syndromes.

[15]  A. Kamali,et al.  High HIV Incidence and Socio-Behavioral Risk Patterns in Fishing Communities on the Shores of Lake Victoria, Uganda , 2012, Sexually transmitted diseases.

[16]  R. Nsubuga,et al.  Heterogeneity of HIV incidence: a comparative analysis between fishing communities and in a neighbouring rural general population, Uganda, and implications for HIV control , 2016, Sexually Transmitted Infections.

[17]  J. Seeley,et al.  HIV/AIDS in fishing communities: Challenges to delivering antiretroviral therapy to vulnerable groups , 2005, AIDS care.

[18]  Glenn Lawyer,et al.  COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification , 2014, Nucleic acids research.

[19]  O. Laeyendecker,et al.  Identifying Transmission Clusters with Cluster Picker and HIV-TRACE. , 2016, AIDS research and human retroviruses.

[20]  M. Zazzi,et al.  HIV-1 Subtype F1 Epidemiological Networks among Italian Heterosexual Males Are Associated with Introduction Events from South America , 2012, PloS one.

[21]  Michel Roger,et al.  High rates of forward transmission events after acute/early HIV-1 infection. , 2007, The Journal of infectious diseases.

[22]  A. Rambaut,et al.  Episodic Sexual Transmission of HIV Revealed by Molecular Phylodynamics , 2008, PLoS medicine.

[23]  Trevor Bedford,et al.  Viral Phylodynamics , 2013, PLoS Comput. Biol..

[24]  T. Bärnighausen,et al.  Localized spatial clustering of HIV infections in a widely disseminated rural South African epidemic. , 2009, International journal of epidemiology.

[25]  J. Seeley,et al.  Fisherfolk are among groups most at risk of HIV: cross-country analysis of prevalence and numbers infected , 2005, AIDS.

[26]  Andrew D. Redd,et al.  Molecular tools for studying HIV transmission in sexual networks , 2014, Current opinion in HIV and AIDS.

[27]  Samantha Lycett,et al.  Automated analysis of phylogenetic clusters , 2013, BMC Bioinformatics.

[28]  A. Kamali,et al.  Voluntary medical male circumcision for HIV prevention in fishing communities in Uganda: the influence of local beliefs and practice , 2016, African journal of AIDS research : AJAR.

[29]  H. Rees,et al.  Transformation of HIV from pandemic to low-endemic levels: a public health approach to combination prevention , 2014, The Lancet.

[30]  Ann M. Dennis,et al.  Using nearly full-genome HIV sequence data improves phylogeny reconstruction in a simulated epidemic , 2016, Scientific Reports.

[31]  Victor De Gruttola,et al.  Extended high viremics: a substantial fraction of individuals maintain high plasma viral RNA levels after acute HIV-1 subtype C infection , 2011, AIDS.

[32]  S. Moore,et al.  Heterogeneity of the HIV epidemic in agrarian, trading, and fishing communities in Rakai, Uganda: an observational epidemiological study. , 2016, The lancet. HIV.

[33]  N. Sewankambo,et al.  Population attributable fraction of incident HIV infections associated with alcohol consumption in fishing communities around Lake Victoria, Uganda , 2017, PloS one.

[34]  F. Gao,et al.  Detection of Phylogenetically Diverse Human Immunodeficiency Virus Type 1 Groups M and O from Plasma by Using Highly Sensitive and Specific Generic Primers , 1999, Journal of Clinical Microbiology.

[35]  P. Kaleebu,et al.  HIV-1 subtype distribution trends and evidence of transmission clusters among incident cases in a rural clinical cohort in southwest Uganda, 2004-2010. , 2013, AIDS research and human retroviruses.

[36]  A. Phillips,et al.  Antiretroviral therapy for prevention of HIV transmission: implications for Europe. , 2013, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[37]  O. Gascuel,et al.  New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. , 2010, Systematic biology.

[38]  H Hui,et al.  The heterosexual human immunodeficiency virus type 1 epidemic in Thailand is caused by an intersubtype (A/E) recombinant of African origin , 1996, Journal of virology.

[39]  Anne-Mieke Vandamme,et al.  Automated subtyping of HIV-1 genetic sequences for clinical and surveillance , 2013 .

[40]  S. Collins,et al.  Community perspective on the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial , 2015, HIV medicine.

[41]  N. Sewankambo,et al.  High Incidence of HIV-1 Infection in a General Population of Fishing Communities around Lake Victoria, Uganda , 2014, PloS one.

[42]  S. Coppens,et al.  Simplified strategy for detection of recombinant human immunodeficiency virus type 1 group M isolates by gag/env heteroduplex mobility assay. Study Group on Heterogeneity of HIV Epidemics in African Cities. , 2000, Journal of virology.

[43]  T. F. Rinke de Wit,et al.  HIV Type 1 transmission networks among men having sex with men and heterosexuals in Kenya. , 2014, AIDS research and human retroviruses.

[44]  Michel Roger,et al.  Phylogenetic inferences on HIV-1 transmission: implications for the design of prevention and treatment interventions. , 2013, AIDS.

[45]  Sikhulile Moyo,et al.  Impact of sampling density on the extent of HIV clustering. , 2014, AIDS research and human retroviruses.

[46]  Andrew J. Tatem,et al.  Spatial accessibility and the spread of HIV-1 subtypes and recombinants , 2012, AIDS.

[47]  D. Cummings,et al.  The Role of Viral Introductions in Sustaining Community-Based HIV Epidemics in Rural Uganda: Evidence from Spatial Clustering, Phylogenetics, and Egocentric Transmission Models , 2014, PLoS medicine.

[48]  T. Quinn,et al.  Association of Medical Male Circumcision and Antiretroviral Therapy Scale-up With Community HIV Incidence in Rakai, Uganda. , 2016, JAMA.

[49]  Ben Murrell,et al.  Social and Genetic Networks of HIV-1 Transmission in New York City , 2017, PLoS pathogens.

[50]  A. Kamali,et al.  Comparison of HIV incidence estimated in clinical trial and observational cohort settings in a high risk fishing population in Uganda: Implications for sample size estimates. , 2016, Vaccine.