HIV transmission networks among transgender women in Los Angeles County, CA, USA: a phylogenetic analysis of surveillance data

Abstract

Background: Transgender women are among the groups at highest risk for HIV infection, with a prevalence of 27·7% in the USA; and despite this known high risk, undiagnosed infection is common in this population. We set out to identify transgender women and their partners in a molecular transmission network to prioritise public health activities.

Methods: Since 2006, HIV protease and reverse transcriptase gene (pol) sequences from drug resistance testing have been reported to the Los Angeles County Department of Public Health and linked to demographic data, gender, and HIV transmission risk factor data for each case in the enhanced HIV/AIDS Reporting System. We reconstructed a molecular transmission network by use of HIV-TRAnsmission Cluster Engine (with a pairwise genetic distance threshold of 0·015 substitutions per site) from the earliest pol sequences from 22 398 unique individuals, including 412 (2%) self-identified transgender women. We examined the possible predictors of clustering with multivariate logistic regression. We characterised the genetically linked partners of transgender women and calculated assortativity (the tendency for people to link to other people with the same attributes) for each transmission risk group.

Findings: 8133 (36·3%) of 22 398 individuals clustered in the network across 1722 molecular transmission clusters. Transgender women who indicated a sexual risk factor clustered at the highest frequency in the network, with 147 (43%) of 345 being linked to at least one other person (adjusted odds ratio [aOR] 2·0, p=0·0002). Transgender women were assortative in the network (assortativity 0·06, p<0·001), indicating that they tended to link to other transgender women. Transgender women were more likely than expected to link to other transgender women (OR 4·65, p<0·001) and cisgender men who did not identify as men who have sex with men (MSM; OR 1·53, p<0·001). Transgender women were less likely than expected to link to MSM (OR 0·75, p<0·001), despite the high prevalence of HIV among MSM. Transgender women were distributed across 126 clusters, and cisgender individuals linked to one transgender woman were 9·2 times more likely to link to a second transgender woman than other individuals in the surveillance database. Reconstruction of the transmission network is limited by sample availability, but sequences were available for more than 40% of diagnoses.

Interpretation: Clustering of transgender women and the observed tendency for linkage with cisgender men who did not identify as MSM, shows the potential to use molecular epidemiology both to identify clusters that are likely to include undiagnosed transgender women with HIV and to improve the targeting of public health prevention and treatment services to transgender women.

Funding: California HIV and AIDS Research Program and National Institutes of Health-National Institute of Allergy and Infectious Diseases.

Figure 1:

Molecular transmission clusters in Los Angeles County with at least one transgender woman (TGW). Node shape denotes gender and color denotes transmission risk factor. Edges represent genetic distance of ≤0.015 substitutions/site. Sex, sexual risk; PWID, people who inject drugs; TGW, transgender women; MSM, men who have sex with men.

Figure 2:

Race/ethnicity of transgender women (TGW) and other individuals with sequence data available in the Los Angeles County dataset. There were 412 individuals in the TGW group compared to 21,986 non-TGW. AI/NA, American Indian/Native Alaskan; PI, Pacific Islander; AA, African American. TGW were less likely to be white than other cases in the dataset (Fisher’s test, p<0.001).

Figure 3:

Demographic breakdown of the persons reported with HIV-1 sequence data in LAC with adjusted odds ratio (AOR) for clustering. The “total” column indicates the number of individuals in the LAC surveillance population in that category and the “clustered” column indicates the number and percentage of individuals in that category who were clustered. The AOR for diagnosis date indicates that individuals diagnosed in each year were 1.18 times more likely to be clustered than individuals sampled in the previous year. Individuals classified as “Early” are those who tested negative for HIV within 6 months before diagnosis. F-PWID, cisgender female person who injects drugs; F-Sex, female with sexual risk; M-PWID, cisgender male person who injects drugs; M-Sex, cisgender male with sexual risk; MSM men who have sex with men; MSM/PWID men who have sex with men and inject drugs; TGM, transgender men; TGW-PWID, transgender women who inject drugs; TGW-Sex, transgender women with sexual risk. * indicates p<0.05, ** p<0.01, and *** p<0.001.

Figure 4:

Assortativity broken down by self-reported risk group. The null distribution of expected assortativity is shown in grey and the observed assortativity for each risk group is displayed in a different color. MSM, men who have sex with men; Sex, sexual risk; TGW-Sex, transgender women with sexual risk; PWID, people who inject drugs; TGW-PWID, transgender women who inject drugs. Significant assortativity is denoted by **p<0.01, ***p<0.001.