Prevalence of Sexually Transmitted Infections Among Transgender Women With and Without HIV in the Eastern and Southern United States.

BACKGROUND: Data on the epidemiology of sexually transmitted infections (STIs) among transgender women (TGW) with and without human immunodeficiency virus (HIV) are limited. METHODS: We analyzed baseline data collected from a cohort of adult TGW across 6 eastern and southern US cities between March 2018 and August 2020 (n = 1018). Participants completed oral HIV screening, provided self-collected rectal and urogenital specimens for chlamydia and gonorrhea testing, and provided sera specimens for syphilis testing. We assessed associations with ≥1 prevalent bacterial STI using modified Poisson regression. RESULTS: Bacterial STI prevalence was high and differed by HIV status: 32% among TGW with HIV and 11% among those without HIV (demographic-adjusted prevalence ratio = 1.91; 95% confidence interval = 1.39-2.62). Among TGW without HIV, bacterial STI prevalence differed by geographic region, race and ethnicity, and gender identity, and was positively associated with reporting >1 sexual partner, hazardous alcohol use, homelessness, having safety concerns regarding transit to health care, and no prior receipt of gender-affirming health services. Among TGW with HIV, older age was inversely associated with bacterial STI. CONCLUSIONS: TGW had a high prevalence of bacterial STIs. The prevalence and correlates of bacterial STI differed by HIV status, highlighting the unique needs and risks of TGW with and without HIV. Tailored interventions may reduce sexual health-related inequities.

An enhanced cross-sectional HIV incidence estimator that incorporates prior HIV test results.

Incidence estimation of HIV infection can be performed using recent infection testing algorithm (RITA) results from a cross-sectional sample. This allows practitioners to understand population trends in the HIV epidemic without having to perform longitudinal follow-up on a cohort of individuals. The utility of the approach is limited by its precision, driven by the (low) sensitivity of the RITA at identifying recent infection. By utilizing results of previous HIV tests that individuals may have taken, we consider an enhanced RITA with increased sensitivity (and specificity). We use it to propose an enhanced estimator for incidence estimation. We prove the theoretical properties of the enhanced estimator and illustrate its numerical performance in simulation studies. We apply the estimator to data from a cluster-randomized trial to study the effect of community-level HIV interventions on HIV incidence. We demonstrate that the enhanced estimator provides a more precise estimate of HIV incidence compared to the standard estimator.

Incidence and prevalence of hepatitis C and B infections among men who have sex with men and transgender women enrolled in a United States HIV vaccine trial.

Background: Rising hepatitis C and B virus (HCV and HBV) rates have been reported in men who have sex with men (MSM) and transgender women (TGW). This study characterizes HCV and HBV infections longitudinally among 2,496 MSM/TGW aged 18-50 years and at risk for HIV acquisition enrolled in an HIV-1 vaccine trial in 18 U.S. cities between 2009-2013. Methods: Participants completed behavioral surveys, HIV testing, and blood collection over 24 months. Of the 2,397 participants who consented for future testing, 1,792 (74.8%) had available paired stored blood samples at baseline and a later timepoint (Month 24 [N = 999]; if unavailable, M12 [N = 775] or M15 [N = 18]). Results: Among 1,792 participants, 98.1% were MSM, 0.8% were TGW, and the median age was 30 years (IQR 24, 40). Participants reported a median number of 3 male sex partners (IQR 1,5) within the past 3 months. Condomless insertive anal sex was reported by 55.8% and condomless receptive anal sex by 46.7%.1.3% reported injection drug use. During follow-up, 1.4% reported pre-exposure prophylaxis (PrEP) use. At baseline 11/1792 (0.61%) participants had HCV infection (HCV AB positive, RNA detectable), with all having persistent detectable RNA and chronic HCV infection at follow-up. Phylogenetic analysis showed no clusters of HCV infection. 8 participants had HCV AB positive, RNA undetectable at baseline and follow-up, representing past HCV infection with clearance; only 2 acquired HCV, which cleared over 12-24 months. At baseline, 2 participants (2/1792 = 0.11%) had positive HBsAg, indicating chronic HBV infection. Over 12-24 months, 4 (4/1790, 0.22%) developed HBsAg positivity; these participants had HBcAB positivity at baseline, thereby likely representing reactivation. There were no new HBV infections during follow-up. Conclusion: Among 1,792 men who have sex with men and transgender women aged 18-50 years and at risk for HIV acquisition enrolled in a U.S. HIV-1 vaccine trial, incident hepatitis C infection rates were extremely low, with no cases of incident hepatitis B infection. These rates of incident HCV infection and HBSAg positivity are lower than previously reported among MSM/TGW.

A Potential Screening Strategy to Identify Probable Syphilis Infections in the Urban Emergency Department Setting.

Background: Syphilis diagnosis in the emergency department (ED) setting is often missed due to the lack of ED-specific testing strategies. We characterized ED patients with high-titer syphilis infections (HTSIs) with the goal of defining a screening strategy that most parsimoniously identifies undiagnosed, untreated syphilis infections. Methods: Unlinked, de-identified remnant serum samples from patients attending an urban ED, between 10 January and 9 February 2022, were tested using a three-tier testing algorithm, and sociodemographic variables were extracted from ED administrative database prior to testing. Patients who tested positive for treponemal antibodies in the first tier and positive at high titer (≥1:8) for nontreponemal antibodies in the second tier were classified as HTSI. Human immunodeficiency virus (HIV) status was determined with Bio-Rad enzyme-linked immunosorbent assay and confirmatory assays. Exact logistic regression and classification and regression tree (CART) analyses were performed to determine factors associated with HTSI and derive screening strategies. Results: Among 1951 unique patients tested, 23 (1.2% [95% confidence interval, .8%-1.8%]) had HTSI. Of those, 18 (78%) lacked a primary care physician, 5 (22%) were HIV positive, and 8 (35%) were women of reproductive age (18-49 years). CART analysis (area under the curve of 0.67) showed that using a screening strategy that measured syphilis antibodies in patients with HIV, without a primary care physician, and women of reproductive age would have identified most patients with HTSI (21/23 [91%]). Conclusions: We show a high prevalence of HTSI in an urban ED and propose a feasible, novel screening strategy to curtail community transmission and prevent long-term complications.

Bivalent mRNA COVID vaccines elicit predominantly cross-reactive CD4+ T cell clonotypes.

Bivalent COVID vaccines containing mRNA for ancestral and Omicron BA.5 spike proteins do not induce stronger T cell responses to Omicron BA.5 spike proteins than monovalent vaccines that contain only ancestral spike mRNA. The reasons for this finding have not been elucidated. Here, we show that healthy donors (HDs) and people living with HIV (PLWH) on antiretroviral therapy mostly target T cell epitopes that are not affected by BA.5 mutations. We use the functional expansion of specific T cells (FEST) assay to determine the percentage of CD4+ T cells that cross-recognize both spike proteins and those that are monoreactive for each protein. We show a predominance of cross-reactive CD4+ T cells; less than 10% percent of spike-specific CD4+ T cell receptors were BA.5 monoreactive in most HDs and PLWH. Our data suggest that the current bivalent vaccines do not induce robust BA.5-monoreactive T cell responses.

Hospital readmissions among adults living with and without HIV in the US: findings from the Nationwide Readmissions Database.

Background: Thirty-day hospital readmission measures quality of care, but there are limited data among people with HIV (PWH) and people without HIV (PWoH) in the era of universal recommendation for antiretroviral therapy. We descriptively compared 30-day all-cause, unplanned readmission risk between PWH and PWoH. Methods: A retrospective cohort study was conducted using the 2019 Nationwide Readmissions Database (2019/01/01-2019/12/31), an all-payer database that represents all US hospitalizations. Index (initial) admissions and readmissions were determined using US Centers for Medicare & Medicaid Services definitions. Crude and age-adjusted risk ratios (aRR) comparing the 30-day all-cause, unplanned readmission risk between PWH to PWoH were estimated using random effect logistic regressions and predicted marginal estimates. Survey weights were applied to all analyses. Findings: We included 24,338,782 index admissions from 18,240,176 individuals. The median age was 52(IQR = 40-60) years for PWH and 61(IQR = 38-74) years for PWoH. The readmission risk was 20.9% for PWH and 12.2% for PWoH (age-adjusted-RR:1.88 [95%CI = 1.84-1.92]). Stratified by age and sex, young female (age 18-29 and 30-39 years) PWH had a higher readmission risk than young female PWoH (aRR = 3.50 [95%CI = 3.11-3.88] and aRR = 4.00 [95%CI = 3.67-4.32], respectively). While the readmission risk increased with age among PWoH, the readmission risk was persistently high across all age groups among PWH. The readmission risk exceeded 30% for PWH admitted for hypertensive heart disease, heart failure, and chronic kidney disease. Interpretation: PWH have a disproportionately higher risk of readmission than PWoH, which is concerning given the aging profile of PWH. More efforts are needed to address readmissions among PWH. Funding: US National Institutes of Health.

Increasing intra- and inter-subtype HIV diversity despite declining HIV incidence in Uganda.

HIV incidence has been declining in Africa with scale-up of HIV interventions. However, there is limited data on HIV evolutionary trends in African populations with waning epidemics. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-five-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from persons living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994 to 2018) and four hyperendemic Lake Victoria fishing communities (2011 to 2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was estimated using the Shannon diversity index and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Evolutionary dynamics were assessed among demographic and behavioral sub-groups, including by migration status. 9,931 HIV sequences were available from 4,999 PLHIV, including 3,060 and 1,939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (p<0.001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (p<0.001). The proportion of viruses classified as recombinants significantly increased by more than four-fold. Inter-subtype HIV diversity has generally increased. While p24 intra-subtype genetic diversity and divergence leveled off after 2014, diversity and divergence of gp41 increased through 2017. Inter- and intra-subtype viral diversity increased across all population sub-groups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics in declining African HIV epidemics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.

Age and gender profiles of HIV infection burden and viraemia: novel metrics for HIV epidemic control in African populations with high antiretroviral therapy coverage.

Introduction: To prioritize and tailor interventions for ending AIDS by 2030 in Africa, it is important to characterize the population groups in which HIV viraemia is concentrating. Methods: We analysed HIV testing and viral load data collected between 2013-2019 from the open, population-based Rakai Community Cohort Study (RCCS) in Uganda, to estimate HIV seroprevalence and population viral suppression over time by gender, one-year age bands and residence in inland and fishing communities. All estimates were standardized to the underlying source population using census data. We then assessed 95-95-95 targets in their ability to identify the populations in which viraemia concentrates. Results: Following the implementation of Universal Test and Treat, the proportion of individuals with viraemia decreased from 4.9% (4.6%-5.3%) in 2013 to 1.9% (1.7%-2.2%) in 2019 in inland communities and from 19.1% (18.0%-20.4%) in 2013 to 4.7% (4.0%-5.5%) in 2019 in fishing communities. Viraemia did not concentrate in the age and gender groups furthest from achieving 95-95-95 targets. Instead, in both inland and fishing communities, women aged 25-29 and men aged 30-34 were the 5-year age groups that contributed most to population-level viraemia in 2019, despite these groups being close to or had already achieved 95-95-95 targets. Conclusions: The 95-95-95 targets provide a useful benchmark for monitoring progress towards HIV epidemic control, but do not contextualize underlying population structures and so may direct interventions towards groups that represent a marginal fraction of the population with viraemia.

Longitudinal patterns in indeterminate HIV rapid antibody test results: a population-based, prospective cohort study.

Rapid HIV tests are critical to HIV surveillance and universal testing and treatment programs. We assessed longitudinal patterns in indeterminate HIV rapid test results in an African population-based cohort. Prospective HIV rapid antibody test results, defined by two parallel rapid tests, among participants aged 15-49 years from three survey rounds of the Rakai Community Cohort Study, Uganda, from 2013 to 2018, were assessed. An indeterminate result was defined as any weak positive result or when one test was negative and the other was positive. A total of 31,405 participants contributed 54,459 person-visits, with 15,713 participants contributing multiple visits and 7,351 participants contributing 3 visits. The prevalence of indeterminate results was 2.7% (1,490/54,469). Of the participants with multiple visits who initially tested indeterminate (n = 591), 40.4% were negative, 18.6% were positive, and 41.0% were indeterminate at the subsequent visit. Of the participants with two consecutive indeterminate results who had a third visit (n = 67), 20.9% were negative, 9.0% were positive, and 70.2% remained indeterminate. Compared to a prior negative result, a prior indeterminate result was strongly associated with a subsequent indeterminate result [adjusted prevalence ratio, 23.0 (95% CI = 20.0-26.5)]. Compared to men, women were more likely to test indeterminate than negative [adjusted odds ratio, 2.3 (95% CI = 2.0-2.6)]. Indeterminate rapid HIV test results are highly correlated within an individual and 0.6% of the population persistently tested indeterminate over the study period. A substantial fraction of people with an indeterminate result subsequently tested HIV positive at the next visit, underscoring the importance of follow-up HIV testing protocols.IMPORTANCERapid HIV tests are a critical tool for expanding HIV testing and treatment to end the HIV epidemic. The interpretation and management of indeterminate rapid HIV test results pose a unique challenge for connecting all people living with HIV to the necessary care and treatment. Indeterminate rapid HIV test results are characterized by any weak positive result or discordant results (when one test is negative and the other is positive). We systematically tested all participants of a Ugandan population-based, longitudinal cohort study regardless of prior test results or HIV status to quantify longitudinal patterns in rapid HIV test results. We found that a substantial fraction (>15%) of participants with indeterminate rapid test results subsequently tested positive upon follow-up testing at the next visit. Our findings demonstrate the importance of follow-up HIV testing protocols for indeterminate rapid HIV test results.

Discordant performance of mpox serological assays.

BACKGROUND: Since July 23, 2022, global mpox cases reached 92,546, with over 31,000 in the United States. Asymptomatic carriage is a critical mechanism influencing the global dissemination of mpox. Seroprevalence studies are crucial for determining the epidemic's true burden, but uncertainties persist in serologic assay performance and how smallpox vaccination may influence assay interpretation. OBJECTIVES: Our study aimed to assess the performance of several diagnostic assays among mpox-positive, vaccinated, and pre-outbreak negative control samples. This investigation sought to enhance our understanding and management of future mpox outbreaks. STUDY DESIGN: Serum samples from 10 mpox-positive, five vaccinated uninfected, and 137 pre-outbreak controls were obtained for serological testing. The mpox-positive samples were obtained around 100 days post symptom onset, and vaccinated patients were sampled approximately 90 days post-vaccination. Multiple diagnostic assays were employed, including four commercial ELISAs (Abbexa, RayBioTech, FineTest, ProteoGenix) and a multiplex assay (MesoScale Diagnostics (MSD)) measuring five mpox and five smallpox antigens. RESULTS: Three commercial ELISA kits had low specificity (<50 %). The Proteogenix ELISA targeting the E8L antigen had a 94 % sensitivity and 87 % specificity. The E8L antigen on the MSD assay exhibited the greatest distinction between exposure groups, with 98 % sensitivity and 93 % specificity. CONCLUSIONS: None of the assays could distinguish between mpox-positive and vaccinated samples. The MSD assay targeting the MPXV E8L antigen demonstrated the greatest differentiation between mpox-positive and pre-outbreak negative samples. Our findings underscore the imperative to identify sensitive and specific assays to monitor population-level mpox exposure and infection.