HIV Risk Behaviors and the Use of Geosocial Networking Dating Apps among Men Who have Sex with Men and Transgender Women in Lima, Peru: a Cross-Sectional Study.

Geosocial networking dating apps (GSN apps) are an increasingly widespread technology used by populations throughout the world to facilitate sexual encounters. Studies from a variety of settings suggest a possible association between GSN app use and HIV risk behaviors, including among sexual and gender minority populations such as men who have sex with men (MSM) and transgender women (TW). However, it remains unclear to what extent GSN apps play a causal role. We explored the relationship between GSN app use and sexual risk behaviors among MSM and TW in Lima, Peru by analyzing data from a multi-site cross-sectional survey assessing both general and partner-specific sexual behaviors. We performed bivariate analysis to estimate the association of GSN app use with different individual and partner-specific factors, then fit multivariable regression models adjusting for age and education. Among 741 total participants (698 MSM, 43 TW), 64% met at least one sex partner in the prior three months using a GSN app. GSN app users were significantly more likely to report engaging in HIV risk behaviors in general, including condomless receptive anal sex, group sex, transactional sex, and sex under the influence of alcohol or drugs. Having condomless anal sex with a given partner was not associated with meeting that partner via GSN app. These findings highlight GSN app users as a particularly vulnerable subpopulation among MSM and TW in Lima. GSN apps could provide a useful vehicle for targeted HIV prevention efforts for priority populations in Peru.

RESUMEN: Las aplicaciones de citas de redes geosociales (aplicaciones GSN) son una tecnología con creciente alcance en todo el mundo usadas para facilitar encuentros sexuales. Diferentes estudios sugieren una posible relación entre uso de aplicaciones GSN y comportamientos de riesgo para VIH entre hombres que tienen sexo con hombres (HSH) y mujeres transgénero (MT). No es claro hasta qué punto aplicaciones GSN tendrían un papel causal directo. Exploramos la relación entre uso de aplicaciones GSN y comportamientos sexuales de riesgo entre HSH y MT en Lima, Perú, analizando datos de una encuesta transversal que evaluó comportamientos sexuales en general y en parejas específicas. Realizamos análisis bivariable para estimar la asociación del uso de aplicaciones GSN con diferentes factores individuales y específicos de la pareja. También aplicamos modelos de regresión multivariables ajustados por edad y educación. Entre 741 participantes totales (698 HSH, 43 MT), 64% conoció al menos a una pareja sexual en los últimos tres meses mediante una aplicación GSN. Los usuarios de aplicaciones GSN fueron significativamente más propensos a reportar comportamientos de riesgo de VIH en general, incluyendo sexo anal receptivo sin condón, y sexo grupal, transaccional y bajo influencia de alcohol o drogas. Tener sexo anal sin condón con una pareja determinada no se asoció con conocer a esa pareja mediante aplicación GSN. Estos hallazgos muestran a usuarios de aplicaciones GSN como una subpoblación particularmente vulnerable entre HSH y MT en Lima. Aplicaciones GSN podrían ser útiles para iniciativas de prevención del VIH en poblaciones prioritarias en Perú.

Acceptability of venue-based HIV testing and prevention interventions for men who have sex with transgender women and transgender women in Lima, Perú: a formative, qualitative study.

BACKGROUND: Despite being at elevated risk for HIV, men who have sex with transgender women (MSTW) are an overlooked population in the global HIV response. Venue-based HIV interventions have previously had success reaching other HIV priority populations, including transgender women (TW). Similar approaches could be applied for MSTW. OBJECTIVE: To evaluate the prospective acceptability of venue-based HIV testing and prevention interventions for MSTW and TW in Lima, Peru. METHODS: In this exploratory qualitative study, we conducted in-depth interviews (IDI) and focus group discussions (FGD) with three types of participants: MSTW (7 IDIs, 1 FGD), TW (1 FGD), and owners of social venues frequented by MSTW/TW in Lima (2 IDIs). We elicited participants' attitudes and perceptions related to the following four hypothetical interventions delivered at social venues in Lima: rapid HIV testing; HIV self-test distribution; condom/lubricant distribution; and enrolment in a mobile app supporting HIV prevention. We performed a mixed deductive-inductive thematic analysis using the framework method, then applied the Theoretical Framework of Acceptability to classify the overall acceptability of each intervention. RESULTS: Condom/lubricant distribution and app-based HIV prevention information were highly acceptable among all participant types. The two HIV testing interventions had relatively lower acceptability; however, participants suggested this could be overcome if such interventions focused on ensuring discretion, providing access to healthcare professionals, and offering appropriate incentives. CONCLUSIONS: Overall, MSTW and TW shared similar favourable attitudes towards venue-based HIV interventions. Venue-based outreach warrants further exploration as a strategy for engaging MSTW and TW in HIV prevention activities.

Viral Load Dynamics in Plasma and Semen When Antiretroviral Therapy Is Initiated During Early HIV-1 Infection.

We assessed human immunodeficiency virus (HIV) load in plasma and semen during primary HIV infection using serial samples of semen and plasma during the first 24 weeks after diagnosis in untreated participants and those who started antiretroviral therapy (ART) immediately at diagnosis. In the absence of treatment, semen viral load was >1000 copies/mL in almost all specimens (83%) collected 2-10 weeks after the estimated date of HIV acquisition and remained >1000 copies/mL in 35% of untreated participants at the last observed time point. Thus, in the absence of ART, semen viral load remained at a level consistent with transmissibility throughout primary infection.

Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence.

Understanding how HIV-1-infected cells proliferate and persist is key to HIV-1 eradication, but the heterogeneity and rarity of HIV-1-infected cells hamper mechanistic interrogations. Here, we used single-cell DOGMA-seq to simultaneously capture transcription factor accessibility, transcriptome, surface proteins, HIV-1 DNA, and HIV-1 RNA in memory CD4+ T cells from six people living with HIV-1 during viremia and after suppressive antiretroviral therapy. We identified increased transcription factor accessibility in latent HIV-1-infected cells (RORC) and transcriptionally active HIV-1-infected cells (interferon regulatory transcription factor [IRF] and activator protein 1 [AP-1]). A proliferation program (IKZF3, IL21, BIRC5, and MKI67 co-expression) promoted the survival of transcriptionally active HIV-1-infected cells. Both latent and transcriptionally active HIV-1-infected cells had increased IKZF3 (Aiolos) expression. Distinct epigenetic programs drove the heterogeneous cellular states of HIV-1-infected cells: IRF:activation, Eomes:cytotoxic effector differentiation, AP-1:migration, and cell death. Our study revealed the single-cell epigenetic, transcriptional, and protein states of latent and transcriptionally active HIV-1-infected cells and cellular programs promoting HIV-1 persistence.

Impact of youth lay health workers on HIV service delivery in South Africa: A pragmatic cluster randomized trial of the Youth Health Africa program.

BACKGROUND: Innovative approaches are needed to increase lay health workers in HIV programs. The Youth Health Africa (YHA) program is a novel approach that places young adults seeking work experience in one-year internships in health facilities to support HIV-related programming (e.g., HIV testing) or administration (e.g., filing). METHODS: We implemented a pragmatic, randomized trial among 20 facilities in Ngaka Modiri Molema district in North West province from October 2020-August 2021 to assess impact of YHA interns on HIV testing, treatment initiation, and retention in care. The primary outcome was proportion of patients tested for HIV. Secondary outcomes assessed HIV positivity, initiation in care, retention in care, and HIV testing among males and adolescents/young adults. We conducted an intention-to-treat analysis accounting for variations in baseline outcomes between control and intervention facilities using difference-in-difference and controlled time series approaches. We repeated this using as-treated groupings for sensitivity analyses. RESULTS: Fifty interns were placed in 20 facilities; thirty-four interns remained at 18 facilities through August 2021. Compared to control facilities, intervention facilities had a greater improvement in HIV testing (ΔΔ+5.7%, 95% Confidence Interval (CI): -3.7%-15.1%) and treatment initiation (ΔΔ+10.3%, 95% CI: -27.8-48.5%), but these differences were not statistically significant. There was an immediate increase in HIV testing in intervention facilities after program interns were placed, which was not observed in control facilities; this difference was significant (ΔΔ+8.4%, 95% CI: 0.5-16.4%, p = 0.036). There were no other differences in outcomes observed between intervention and control facilities. CONCLUSION: This was largely a null trial, but there were signals that program interns may have positive impact on HIV testing and treatment initiation. As implemented in this study, addition of YHA program interns had little impact on facility-based HIV service delivery. A higher number of interns placed per facility may be necessary to affect HIV services. TRIAL REGISTRATION: Registration: This trial was registered with the ISRCTN (Registration number: ISRCTN67031403) in October 2022.

Protocol for evaluating mechanistic pathways associated with HIV acquisition via nested Least Absolute Shrinkage and Selective Operator analysis.

Statistical analysis to evaluate mechanistic pathways can be limited by non-causal associations as well as co-linearity of high-dimensional data. Here, we present a protocol evaluating statistical associations between multiple exposure variables (sociodemographic and behavioral), immune biomarkers, and HIV acquisition. We describe steps for study setup, combining Least Absolute Shrinkage and Selective Operator with the standard regression approach, and building nested models. This approach can determine to what extent associations between risks for exposure contributes to HIV acquisition with or without associated changes in immune activation. For complete details on the use and execution of this protocol, please refer to Bender Ignacio et al.1.

A Quantitative Intersectionality Analysis of HIV/STI Prevention and Healthcare Access Among Transgender and Nonbinary People.

BACKGROUND: Transgender and nonbinary people experience substantial barriers to accessing healthcare, including prevention of HIV and other sexually transmitted infections (HIV/STI), due to structural inequities. We examined differences in insurance, HIV/STI prevalence, testing, and preexposure prophylaxis use among transgender and nonbinary people living in Washington State by race and ethnicity and gender. METHODS: We pooled data from five 2019-2021 Washington State HIV/STI surveillance data sources to obtain a large and diverse sample of 1648 transgender and nonbinary participants. We calculated the risk difference (RD) for each outcome and used Poisson regression to estimate a surrogate measure of additive interaction-attributable proportion (AP)-that measures the proportion of the excess prevalence of the outcome observed at the intersection of gendered and racialized experience, beyond that expected from gender or race and ethnicity alone. RESULTS: Participants reported overall high levels of poverty (29% incomes <$15,000 and 7% unstable housing). Certain groups, especially racial/ethnic minority transgender women, were disproportionately impacted by HIV/STIs (RDs from 20% to 43% and APs from 50% to 85%) and less likely to currently have insurance (RDs from 25% to 39% and APs from 74% to 93%) than that expected based on gendered or racialized experience alone. CONCLUSIONS: Our findings highlight the heterogeneity in insurance access, HIV/STI positivity, and prevention utilization within transgender communities. We observed that a large proportion of increased HIV/STI prevalence among racial/ethnic minority transgender women was attributable to the intersection of gender and race and ethnicity. Our findings highlight the importance of trans-inclusive models of HIV/STI prevention that address multilevel barriers rooted in cissexism and structural racism.

Observational study of effects of HIV Acquisition and Antiretroviral Treatment on Biomarkers of Systemic Immune Activation.

Objective: Assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women. Design: A retrospective study comparing inflammatory biomarkers in participants' specimens collected before and after ≥2 years of effective ART. Methods: Inflammatory biomarkers were measured in four longitudinally collected plasma specimens, including two plasma specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression. Biomarkers were quantified by enzyme-linked immuno-assay or Meso Scale Discovery. Statistical measures compared intra-participant and between-group changes in biomarkers. Results: Across 50 participants, the levels of C-reactive protein (CRP), monocyte chemo-attractant protein-1, tumor necrosis factor-α and interferon gamma-induced protein-10 significantly increased while leptin and lipopolysaccharide binding protein (LBP) significantly decreased following HIV infection. Randomization to deferred-ART initiation was associated with greater increases in CRP and no decreases in LBP. Multiple biomarkers varied significantly within participants' two pre-infection or two post-ART-suppression specimens. Conclusions: Acquisition of HIV appeared to induce systemic inflammation, with elevation of biomarkers previously associated with infections and cardiovascular disease. Initiation of ART during the early weeks of infection tempered the increase in pro-inflammatory biomarkers compared to those who delayed ART for ~24 weeks after HIV diagnosis, perhaps because immediate-ART limited the size of the HIV reservoir or limited immune dysregulation. Some but not all biomarkers appeared sufficiently stable to assess intraparticipant changes over time. Given that pro-inflammatory biomarkers predict multiple co-morbidities, our findings suggest that immediate-ART initiation may improve health outcomes.

Does a youth intern programme strengthen HIV service delivery in South Africa? An interrupted time-series analysis.

INTRODUCTION: Since 2018, Youth Health Africa (YHA) has placed unemployed young adults at health facilities across South Africa in 1-year non-clinical internships to support HIV services. While YHA is primarily designed to improve employment prospects for youth, it also strives to strengthen the health system. Hundreds of YHA interns have been placed in programme (e.g. HIV testing and counselling) or administrative (e.g. data and filing) roles, but their impact on HIV service delivery has not been evaluated. METHODS: Using routinely collected data from October 2017 to March 2020, we conducted an interrupted time-series analysis to explore the impact of YHA on HIV testing, treatment initiation and retention in care. We analysed data from facilities in Gauteng and North West where interns were placed between November 2018 and October 2019. We used linear regression, accounting for facility-level clustering and time correlation, to compare trends before and after interns were placed for seven HIV service indicators covering HIV testing, treatment initiation and retention in care. Outcomes were measured monthly at each facility. Time was measured as months since the first interns were placed at each facility. We conducted three secondary analyses per indicator, stratified by intern role, number of interns and region. RESULTS: Based on 207 facilities hosting 604 interns, YHA interns at facilities were associated with significant improvements in monthly trends for numbers of people tested for HIV, newly initiated on treatment and retained in care (i.e. loss to follow-up, tested for viral load [VL] and virally suppressed). We found no difference in trends for the number of people newly diagnosed with HIV or the number initiating treatment within 14 days of diagnosis. Changes in HIV testing, overall treatment initiation and VL testing/suppression were most pronounced where there were programme interns and a higher number of interns; change in loss to follow-up was greatest where there were administrative interns. CONCLUSIONS: Placing interns in facilities to support non-clinical tasks may improve HIV service delivery by contributing to improved HIV testing, treatment initiation and retention in care. Using youth interns as lay health workers may be an impactful strategy to strengthen the HIV response while supporting youth employment.

Heterogeneity in HIV/Sexually Transmitted Infection Prevalence and Prevention Among the Partners of Transgender and Nonbinary People.

BACKGROUND: Transgender and nonbinary (TNB) people are diverse in their sexual orientation and partnerships. We describe the epidemiology of HIV/sexually transmitted infection (STI) prevalence and prevention utilization among the partners of TNB people in Washington State. METHODS: We pooled data from five 2017 to 2021 cross-sectional HIV surveillance data sources to generate a large sample of TNB people and cisgender people who had a TNB partner in the past year. We described characteristics of recent partners of trans women, trans men, and nonbinary people and used Poisson regression to assess if having a TNB partner was associated with self-reported HIV/STIs prevalence, testing, and preexposure prophylaxis (PrEP) use. RESULTS: Our analysis included 360 trans women, 316 trans men, 963 nonbinary people, 2896 cis women, and 7540 cis men. Overall, 9% of sexual minority cis men, 13% of sexual minority cis women, and 36% of TNB participants reported having any TNB partners. There was significant heterogeneity in HIV/STI prevalence, testing, and PrEP use among the partners of TNB people by study participant gender and the gender of their sex partners. In regression models, having a TNB partner was associated with a higher likelihood of HIV/STI testing and PrEP use but was not associated with higher HIV prevalence. CONCLUSIONS: We observed significant heterogeneity in HIV/STI prevalence and preventative behaviors among the partners of TNB people. Given that TNB people are diverse in their sexual partnerships, there is a need to better understand individual-, dyad-, and structural-level factors that facilitate HIV/STI prevention across these diverse partnerships.

Acute retroviral syndrome is associated with lower CD4 + T cell nadir and delayed viral suppression, which are blunted by immediate antiretroviral therapy initiation.

OBJECTIVES: To describe the prevalence of acute retroviral syndrome (ARS) and associated findings during primary HIV, and explore the relationship of ARS to clinical, virological, and immunological outcomes within a longitudinal screen, retest and treat study that minimized ascertainment bias. DESIGN: We evaluated ARS symptoms and signs among 216 persons with acute and early incident HIV within the Sabes study of timing of antiretroviral therapy (ART) initiation during primary HIV in Peru. METHODS: We evaluated patient reported symptoms and signs during primary HIV and used logistic regression and generalized linear models to evaluate associations with CD4 + and CD8 + T cell counts, HIV viral load, and a panel of 23 soluble markers of immune activation. RESULTS: Sixty-one percent of participants had at least one ARS finding and 35% had at least 3. More ARS findings were reported in those enrolled within a month of estimated date of detectable infection (EDDI). Having more ARS signs/symptoms was associated with increased risk of CD4 + cell decrease below 350 cells/ml within the first 24 weeks, failure to suppress HIV viral load, and was most strongly associated with elevated IP-10. Immediate ART blunted effects on symptoms, CD4 + cell count and viral load, as associations were strongest in the arm that started ART after 24 weeks. Detrimental associations of ARS with CD4 + counts, and CD4 + /CD8 + ratio were not maintained at 2 or 4 years. CONCLUSIONS: ARS has marked associations with short-term immunologic function and virologic suppression, which were mitigated in participants randomized to initiate ART immediately during primary infection.

"They are gaining experience; we are gaining extra hands": a mixed methods study to assess healthcare worker perceptions of a novel strategy to strengthen human resources for HIV in South Africa.

BACKGROUND: Lay health workers (LHWs) can support the HIV response by bridging gaps in human resources for health. Innovative strategies are needed to expand LHW programs in many low- and middle-income countries. Youth Health Africa (YHA) is a novel LHW approach implemented in South Africa that places young adults needing work experience in one-year non-clinical internships at health facilities to support HIV programs (e.g., as HIV testers, data clerks). While research suggests YHA can increase HIV service delivery, we need to understand healthcare worker perceptions to know if this is an acceptable and appropriate approach to strengthen human resources for health and healthcare delivery. METHODS: We conducted a convergent mixed methods study to assess healthcare worker acceptance and perceived appropriateness of YHA as implemented in Gauteng and North West provinces, South Africa and identify issues promoting or hindering high acceptability and perceived appropriateness. To do this, we adapted the Johns Hopkins Measure of Acceptability and Appropriateness to survey healthcare workers who supervised interns, which we analyzed descriptively. In parallel, we interviewed frontline healthcare workers who worked alongside YHA interns and conducted an inductive, thematic analysis. We merged quantitative and qualitative results using the Theoretical Framework of Acceptability to understand what promotes or hinders high acceptance and appropriateness of YHA. RESULTS: Sixty intern supervisors responded to the survey (91% response rate), reporting an average score of 3.5 for acceptability and 3.6 for appropriateness, on a four-point scale. Almost all 33 frontline healthcare workers interviewed reported the program to be highly acceptable and appropriate. Perceptions that YHA was mutually beneficial, easy to integrate into facilities, and helped facilities be more successful promoted a strong sense of acceptability/appropriateness amongst healthcare workers, but this was tempered by the burden of training interns and limited program communication. Overall, healthcare workers were drawn to the altruistic nature of YHA. CONCLUSION: Healthcare workers in South Africa believed YHA was an acceptable and appropriate LHW program to support HIV service delivery because its benefits outweighed its costs. This may be an effective, innovative approach to strengthen human resources for HIV services and the broader health sector.

Facilitating Next-Generation Pre-Exposure Prophylaxis Clinical Trials Using HIV Recent Infection Assays: A Consensus Statement from the Forum HIV Prevention Trial Design Project.

Standard-of-care HIV pre-exposure prophylaxis (PrEP) is highly efficacious, but uptake of and persistence on a daily oral pill is low in many settings. Evaluation of alternate PrEP products will require innovation to avoid the unpractically large sample sizes in noninferiority trials. We propose estimating HIV incidence in people not on PrEP as an external counterfactual to which on-PrEP incidence in trial subjects can be compared. HIV recent infection testing algorithms (RITAs), such as the limiting antigen avidity assay plus viral load used on specimens from untreated HIV positive people identified during screening, is one possible approach. Its feasibility is partly dependent on the sample size needed to ensure adequate power, which is impacted by RITA performance, the number of recent infections identified, the expected efficacy of the intervention, and other factors. Screening sample sizes to support detection of an 80% reduction in incidence for 3 key populations are more modest, and comparable to the number of participants in recent phase III PrEP trials. Sample sizes would be significantly larger in populations with lower incidence, where the false recency rate is higher or if PrEP efficacy is expected to be lower. Our proposed counterfactual approach appears to be feasible, offers high statistical power, and is nearly contemporaneous with the on-PrEP population. It will be important to monitor the performance of this approach during new product development for HIV prevention. If successful, it could be a model for preventive HIV vaccines and prevention of other infectious diseases.

Correlates of condomless anal intercourse with different types of sexual partners among men who have sex with men and transgender women in Lima, Peru.

CLINICAL TRIAL REGISTRATION: The Sabes study was registered in March 2013 with the National Institutes of Health at ClinicalTrials.gov (identifier: NCT01815580).

Dynamic immune markers predict HIV acquisition and augment associations with sociobehavioral factors for HIV exposure.

Prior studies attempting to link biomarkers of immune activation with risk of acquiring HIV have relied on cross sectional samples, most without proximity to HIV acquisition. We created a nested case-control study within the Sabes study in Peru, and assessed a panel of plasma immune biomarkers at enrollment and longitudinally, including within a month of diagnosis of primary HIV or matched timepoint in controls. We used machine learning to select biomarkers and sociobehavioral covariates predictive of HIV acquisition. Most biomarkers were indistinguishable between cases and controls one month before HIV diagnosis. However, levels differed between cases and controls at study entry, months to years earlier. Dynamic changes in IL-2, IL-7, IL-10, IP-10 and IL-12, rather than absolute levels, jointly predicted HIV risk when added to traditional risk factors, and there was modest effect modification of biomarkers on association between sociobehavioral risk factors and HIV acquisition.

Continued attendance in a PrEP program despite low adherence and non-protective drug levels among adolescent girls and young women in Kenya: Results from a prospective cohort study.

BACKGROUND: In sub-Saharan Africa (SSA), adolescent girls and young women (AGYW) ages 15 to 24 years represent <10% of the population yet account for 1 in 5 new HIV infections. Although oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) can be highly effective, low persistence in PrEP programs and poor adherence have limited its ability to reduce HIV incidence among women. METHODS AND FINDINGS: A total of 336 AGYW participating in the PEPFAR-funded DREAMS PrEP program in western Kenya were enrolled into a study of PrEP use conducted between 6/2019 to 1/2020. AGYW, who used daily oral TDF/FTC, completed interviews and provided dried blood spots (DBS) for measurement of tenofovir-diphosphate (TFV-DP) concentrations at enrollment and 3 months later, and 176/302 (58.3%, 95% confidence interval [95% CI 52.3 to 63.8]) met our definition of PrEP persistence: having expressed intention to use PrEP and attended both the second interview and an interim refill visit. Among AGYW with DBS taken at the second interview, only 9/197 (4.6%, [95% CI 1.6 to 7.5]) had protective TFV-DP levels (≥700 fmol/punch) and 163/197 (82.7%, [95% CI 77.5 to 88]) had levels consistent with no recent PrEP use (<10 fmol/punch). Perception of being at moderate-to-high risk for HIV if not taking PrEP was associated with persistence (adjusted odds ratio, 10.17 [95% CI 5.14 to 20.13], p < 0.001) in a model accounting for county of residence and variables that had p-value <0.1 in unadjusted analysis (age, being in school, initiated PrEP 2 to 3 months before the first interview, still active in DREAMS, having children, having multiple sex partners, partner aware of PrEP use, partner very supportive of PrEP use, partner has other partners, AGYW believes that a partner puts her at risk, male condom use, injectable contraceptive use, and implant contraceptive use). Among AGYW who reported continuing PrEP, >90% indicated they were using PrEP to prevent HIV, although almost all had non-protective TFV-DP levels. Limitations included short study duration and inclusion of only DREAMS participants. CONCLUSIONS: Many AGYW persisted in the PrEP program without taking PrEP frequently enough to receive benefit. Notably, AGYW who persisted had a higher self-perceived risk of HIV infection. These AGYW may be optimal candidates for long-acting PrEP.

Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use.

Background: Primary human immunodeficiency virus (HIV) is characterized by dynamic changes in viral load and innate and adaptive immune responses; it is unclear the extent to which time from acquisition to antiretroviral therapy (ART) initiation and substance use impact these immunologic changes. Methods: We studied plasma immune activation biomarkers, viral load, and CD4+ and CD8+ cell counts in participants from the Sabes primary infection study in Peru, who had been randomized to begin ART immediately after diagnosis vs 24 weeks later. We modeled influence of substance use and duration of HIV infection on biomarkers at baseline and over 24 weeks. Results: Compared to participants enrolled >30 days after HIV acquisition, participants enrolled during acute infection (≤30 days) had higher mean interferon (IFN)-γ and IFN-α2a (1.7-fold and 3.8-fold interquartile range [IQR] higher, respectively). Participants enrolled >30 days after HIV acquisition had higher mean baseline CD8+ cell count (2.7 times the IQR). Alcohol use (positive phosphatidylethanol level) was associated with elevated IFN-γ, tumor necrosis factor alpha (TNF-α), and interleukin 12p70 (IL-12p70), and smoking was associated with higher macrophage inflammatory protein 1α, TNF-α, and IL-12p70. Most biomarkers declined more quickly in participants who initiated ART immediately; however, substance use and duration of HIV infection at enrollment had little influence on rate of decline. Conclusions: IFN-γ and other biomarkers are elevated during early primary infection, when exposure to HIV antigens is high. Immune activation decreased most quickly in those who started ART during acute/early primary infection. Higher CD8+ cell counts and a trend toward higher soluble CD163 levels during the 30 days after acquisition suggest the onset of compensatory responses and immune exhaustion.

Mycobacterium tuberculosis infection, immune activation, and risk of HIV acquisition.

BACKGROUND: Although immune activation is associated with HIV acquisition, the nature of inflammatory profiles that increase HIV risk, which may include responses to M. tuberculosis (Mtb) infection, are not well characterized. METHODS: We conducted a nested case-control study using cryopreserved samples from persons who did and did not acquire HIV during the multinational Step clinical trial of the MRKAd5 HIV-1 vaccine. PBMCs from the last HIV-negative sample from incident HIV cases and controls were stimulated with Mtb-specific antigens (ESAT-6/CFP-10) and analyzed by flow cytometry with intracellular cytokine staining and scored with COMPASS. We measured inflammatory profiles with five Correlates of TB Risk (CoR) transcriptomic signatures. Our primary analysis examined the association of latent Mtb infection (LTBI; IFNγ+CD4+ T cell frequency) or RISK6 CoR signature with HIV acquisition. Conditional logistic regression analyses, adjusted for known predictors of HIV acquisition, were employed to assess whether TB-associated immune markers were associated with HIV acquisition. RESULTS: Among 465 participants, LTBI prevalence (21.5% controls vs 19.1% cases, p = 0.51) and the RISK6 signature were not higher in those who acquired HIV. In exploratory analyses, Mtb antigen-specific polyfunctional CD4+ T cell COMPASS scores (aOR 0.96, 95% CI 0.77, 1.20) were not higher in those who acquired HIV. Two CoR signatures, Sweeney3 (aOR 1.38 (1.07, 1.78) per SD change) and RESPONSE5 (0.78 (0.61, 0.98)), were associated with HIV acquisition. The transcriptomic pattern used to differentiate active vs latent TB (Sweeney3) was most strongly associated with acquiring HIV. CONCLUSIONS: LTBI, Mtb polyfunctional antigen-specific CD4+ T cell activation, and RISK6 were not identified as risks for HIV acquisition. In exploratory transcriptomic analyses, two CoR signatures were associated with HIV risk after adjustment for known behavioral and clinical risk factors. We identified host gene expression signatures associated with HIV acquisition, but the observed effects are likely not mediated through Mtb infection.