Risk Of HIV Acquisition Research Articles

Network determinants of relationship influence on HIV prevention decision-making among people in the social networks of women who have experienced incarceration in the US.

Many cisgender women in the US who have experienced incarceration are at substantial risk for HIV acquisition after they return to the community. Various network interventions have been leveraged for HIV prevention in this population. The objective of this study was to identify network and relationship determinants of influence on HIV prevention decisions, including PrEP. We conducted interviews with a network mapping exercise with participants recruited from the social and sexual networks of women who had experienced incarceration. Participants enumerated important individuals in their lives from the past six months and provided demographic and relationship data as well as whether each relationship influenced their HIV prevention decisions. We abstracted network data from the interview transcripts and described the data set using descriptive statistics and network density graphs. To measure associations between characteristics at each level and whether a relationship was considered influential regarding PrEP decision-making, we use multiple logistic regression with random intercepts for each respondent. We interviewed 32 participants, average age 33.5 years (SD = 8.98), majority female (n = 28, 87.5%), white (n = 23, 71.8%), heterosexual/straight (n = 25, 78.1%), and with a personal history of incarceration (n = 29, 90%). They reported 253 relationships (119 family, 116 friend, 18 sexual relationships). Most adult network members had used drugs or alcohol (n = 182, 80.9%), and of those, 30.8% had used them with the participant (n = 53). The mean network size was 7 (SD = 4) and network density was 52.2%. In the full model, significant positive predictors of an influential relationship included participant non-heterosexual identity (OR 27.8), older average age in the network (OR 3.9 per standard deviation), and being a current or prior sexual partner (OR 10.1). Significant negative predictors included relationships with individuals who use or had used drugs (OR 0.28), longer average relationship duration in the network (OR 0.09) and being in a network with at least one sexual partner (OR 0.2). There are significant positive and negative determinants of relationship influence related to PrEP at individual-, dyad-, relationship-, and network-levels. These support using nuanced network approaches to behavior change that respect and leverage the diversity of relationships that comprise the social networks of women who have experienced incarceration.

HIV risks and transactional sex among Swedish-born MSM and foreign-born MSM in Sweden

Abstract Background Transactional sex, which includes exchanging sex for material goods, services, or money, is a key HIV risk factor. Risk patterns associated with transactional sex among men who have sex with men (MSM) in Sweden, where buying sexual services is illegal, have not been examined earlier. This study aims to assess whether transactional sex (both buying and selling), country of birth, and migration-related factors (described by country of origin) are associated with self-reported HIV status among MSM in Sweden. Methods We analyzed secondary data from the 2017 European MSM Internet Survey (EMIS-2017), including participants reporting to live in Sweden (n = 4443). Using multivariate logistic regression analysis, we aimed to understand factors related to involvement in transactional sex and risk of HIV acquisition. Results Among the respondents, 5.4% reported living with HIV, with 8.8% of foreign-born MSM and 4.8% of Swedish-born MSM. The multivariable analysis showed that both selling and buying sex in the past five years increased the odds of reporting a positive HIV serostatus among all participants. Stratifying by transactional sex exposure and country of birth showed an HIV prevalence increase for all groups. Foreign-born selling or buying sex ever in the last five years had the highest prevalence of all groups (ranging from 17.8 to 19.1%). Other factors associated with a positive HIV status were age, outness, sex with a woman in the past twelve months, and condom use. Conclusions The relatively high reported HIV prevalence supports the need for HIV prevention, including the scale-up of access to pre-exposure prophylaxis to foreign-born MSM. A transparent discussion about risk factors and socioeconomic structures contributing to risk behaviors, including transactional sex, is needed. Key messages • Engaging in transactional sex increases the HIV risk among MSM in Sweden, particularly among foreign-born MSM. • HIV prevention needs to address the socioeconomic factors contributing to risky behaviors, such as transactional sex.

Extragenital self-collection testing for gonorrhea and chlamydia: A feasibility study for expanding STI screening in the Veterans Health Administration.

Rectal and pharyngeal infections with gonorrhea and chlamydia are of concern because they are associated with higher risk of HIV acquisition. Extragenital screening in asymptomatic persons at high risk may have the potential to reduce the incidence of these sexually transmitted infections (STIs). Several testing platforms are available for the testing of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using nucleic acid amplification tests (NAATs). Self-collected extragenital samples are currently not approved by the US Food and Drug Administration in any NAAT platform. This study compares the analytical performance of self-collected extragenital specimens to that of clinician-collected specimens. We performed a multicenter/multiplatform validation study as a National Veterans Health Administration Pathology and Laboratory Medicine quality improvement project, with 9 different participating sites. Self-collected specimens were obtained at the same time as clinician-collected specimens. Clinician-collected specimens were used as the gold standard to evaluate the sensitivity and specificity of self-collection. A total of 2324 individual tests were analyzed (501 rectal and 661 oropharyngeal). The sensitivity was 94.44% for CT and 100% for NG for rectal specimens, whereas it was 100% for CT and 97.22% for NG for oral specimens. Specificity for oral specimens was 99.85% for CT and 99.36% for NG, whereas for rectal specimens, it was 99% for CT and NG. Self-collected specimens for extragenital CT/NG testing are highly sensitive and specific, with negative predictive values of 100%. Self-collection has the potential to overcome a major barrier for STI screening by providing an accessible, convenient, and patient-centered alternative.

Addressing barriers to implementing and scaling PrEP in carceral settings: Applying insights from implementation science.

Within the United States, individuals experiencing incarceration are at higher risk for HIV acquisition compared to the general population, yet may face additional difficulty engaging in HIV prevention clinical services. HIV pre-exposure prophylaxis (PrEP) is an effective approach to preventing HIV transmission, and the Centers for Disease Control (CDC) recommends that PrEP be offered in carceral settings, particularly during the vulnerable community re-entry period. However, there have been few efforts to scale PrEP in this setting. Based on our experience implementing PrEP in Rhode Island's state carceral system, we have identified potential approaches to overcoming barriers to PrEP use in this unique practice environment by utilizing the implementation research logic model (IRLM). We then evaluated specific implementation determinants and barriers as well as strategies used to overcome those barriers to effectively scale PrEP in this setting. We developed a "toolkit," or 14-step guide, for others in the field to use for implementing PrEP in carceral settings including the development and use of clinical protocols as well as community linkage strategies. Our experiences with barriers in the carceral setting, identifying and leveraging implementation strategies, allowed us to develop a "toolkit" to guide other PrEP implementation projects in carceral settings. We encourage others to scale-out our work to other carceral settings to better reach and engage a group of individuals both at elevated risk for HIV and currently underserved by HIV prevention strategies, including PrEP.

A-284 Development of a Low Positive Molecular Control for Mycoplasma genitalium and Trichomonas vaginalis Screening

Abstract Background Mycoplasma genitalium (MG) is a sexually transmitted gram -negative bacteria that infects the urinary and genital tracts. Trichomonas vaginalis (TV) is a protozoan parasite and is the most common curable sexually transmitted infection (STI) worldwide. TV/ MG infections often go unrecognized because infected individuals are either asymptomatic or have symptoms similar to other infections of the urogenital tract (cervicitis in females and urethritis in males). Left untreated, TV/MG can lead to severe health complications including pelvic inflammatory disease, adverse pregnancy outcomes such as preterm delivery and miscarriage, increased risk of HIV acquisition, sexually acquired reactive arthritis, and infertility. The rates of STIs are increasing and differentiating among different STIs is critical to ensure patients receive effective treatment. Amplified nucleic acid based tests (NAATs) have emerged as the gold standard for diagnosis of TV/MG infections due to their high sensitivity and high throughput using a variety of clinical samples including male and female urine. This study describes work to develop a low positive quality control material in human urine for TV/MG amplified nucleic acids tests. Methods A method was developed to eliminate residual enzymatic activity from raw, pooled human urine from both genders to create a homogeneous diluent that supports analyte stability. The urine diluent was tested for viral pathogens (HIV-1, HCV, HBV) and ensure urine proteins and chemistry analytes were within acceptable limits. TaqMan® assays for TV (targeting RNA polymerase Rpb1 gene) and MG (targeting SMC Chromosome segregation gene) were developed and qualified for digital PCR quantitation of these organisms using the BioRad QX200 system. Cultured Trichomonas vaginalis strain C-1:NIH and Mycoplasma genitalium strain G37 were spiked into the urine diluent along with 0.09% sodium azide as a preservative. The concentration of TV and MG was guided by digital PCR quantitation throughout formulation and the final product was tested on Abbott Alinity m STI Panel, Hologic Aptima® Mycoplasma genitalium Assay, and Hologic Aptima® Trichomonas vaginalis Assay. Results Three independent lots were produced that were each detected for both TV and MG on the Abbott Alinity m STI panel. The concentration of the controls targeted a cycle number (CN) of ∼27 for TV and ∼32 for MG and were within acceptable limits. The lots were also positive for TV and MG when tested on the Hologic Aptima TV and MG assays. Accelerated stability studies showed that the product is stable throughout 2 years of shelf life when stored frozen at -20 °C, but is also stable for up to 30 days at 2-8 °C refrigerated storage. Conclusions LGC Clinical Diagnostics is developing a stable, whole organism molecular control material for use with in vitro diagnostic test methods that detect TV and MG. The product will fulfill an unmet need for molecular quality controls for STI testing that are formulated in a true patient-like matrix like urine. This study helps ensure the molecular control will be a low positive on leading diagnostic assays, be consistent batch to batch, and have the needed stability to meet the needs of clinical testing labs.

Associations of HIV pre-exposure prophylaxis (PrEP) indication, HIV risk perception and unwillingness to use PrEP among people who inject drugs in Baltimore, MD

BackgroundPerceived HIV risk may impact willingness to initiate PrEP among people who inject drugs (PWID). MethodsWe analyzed baseline data from PrEP eligible PWID in Baltimore, MD. Risk perception was assessed by PWID relative to the average risk of their age group categorized as: higher-than, lower-than, or about average. Participants were informed of PrEP for HIV prevention and asked about their willingness to use daily PrEP. Associations of PrEP indication (categorized as injection risk only vs any sexual risk), perceived HIV risk and non-willingness to use PrEP was assessed using generalized linear models. ResultsAmong 489 participants, 61 % were male, 66 % were Black and mean age was 46 years. One-third (35 %) of the participants were aware of PrEP and <1 % had used PrEP in the prior 30 days. Overall, 30 % of PWID reported lower-than-average perceived HIV risk and 18 % reported non-willingness to use PrEP. Participants with injection risk only were more likely (aOR: 2.75; 95 %CI: 1.60 – 4.73) to report having lower-than-average perceived HIV risk compared to those with any sexual risk. Participants with lower-than-average perceived risk were more likely to report non-willingness to use PrEP compared to those with higher perceived risk (adjusted PR: 1.91; 95 %CI: 1.18 – 3.10). ConclusionA considerable proportion of PWID eligible for PrEP reported having low risk of HIV acquisition despite being eligible for PrEP. Consistent and tailored PrEP messaging that addresses drug use HIV risk perception may be critical to increasing PrEP uptake among PWID.

Trajectories of Adherence to Oral Pre-exposure Prophylaxis and Risks of HIV and Sexually Transmitted Infections.

Pre-exposure prophylaxis (PrEP) effectiveness is highly dependent on medication adherence, which is associated with differential HIV risks and possibly sexually transmitted infection (STI). This retrospective cohort study of PrEP users (01/01/2012-12/31/2021) used the MarketScan database of commercially insured enrollees to examine PrEP adherence trajectory groups' associations with HIV and STI acquisition risks. Distinct PrEP adherence trajectories were identified by group-based trajectory modeling among individuals who used oral PrEP. The primary outcome was HIV acquisition incidence, and secondary was STI rate, compared among trajectory groups. Inverse probability treatment weighting time-varying Cox proportional hazards models assessed HIV acquisition, and Poisson regression models assessed STI. Among 23 258 oral PrEP users, 4 distinct PrEP adherence patterns were identified: minimal use (10.5% of the cohort), rapidly declining (25.4%), gradually declining (24.3%), and consistently high (39.8%). Compared with the minimal use group, the gradually declining (adjusted hazard ratio [AHR], 0.53; 95% CI, 0.31-0.90) and consistently high (AHR, 0.50; 95% CI, 0.30-0.84) PrEP adherence groups showed decreased HIV incidence risks. Compared with the minimal use group, the rapidly declining (adjusted incidence rate ratio [AIRR], 1.35; 95% CI, 1.07-1.72), gradually declining (AIRR, 1.73; 95% CI, 1.38-2.18), and consistently high (AIRR, 2.06; 95% CI, 1.64-2.58) groups were associated with increased STI risk. These findings underscore the benefits of continuing and remaining adherent to PrEP and may also inform public health strategies, clinical guidelines, and interventions aimed at maximizing the effectiveness of PrEP in reducing new HIV infections while developing targeted strategies to prevent STIs with PrEP use.

Correlation of APOE polymorphism, expression, and plasma levels with cardiac comorbidities among lipodystrophy in HIV-infected patients

Lipodystrophy in HIV-infected patients (LDHIV) includes morphological and metabolic abnormalities, including lipid and glucose metabolism. ApoE plays a role in the transport and clearance of lipoprotein. In the general population, ApoE 112 (rs429358) and 158 (rs7412) polymorphisms were linked to severe dyslipidemia. Therefore, we investigated ApoE polymorphism using PCR-RFLP in 200 HIV patients (100 with HIV-associated lipodystrophy (HIVLD), 100 without HIVLD), as well as 100 healthy controls. We also assessed ApoE expression using qRT-PCR and measured its level using ELISA. The APOE 4/4, 3/4, and 2/4 genotypes have been associated with a decreased risk of HIV-1 infection. (P = 0.0001, OR = 0.18; P = 0.006, OR = 0.87; P = 0.006, OR = 0.09) when compared between HIV-positive individuals and healthy controls. Conversely, APOE allele 2 was linked to a higher risk of acquiring HIV-1 (P = 0.03, OR = 3.02). APOE allele 2 was linked to a higher likelihood of HIVLD severity when compared between patients with and without HIVLD (P = 0.05, OR = 2.82). When comparing patients with HIVLD to healthy controls, the APOE 4/4 and 2/4 genotypes as well as allele 4 were linked with the reduced risk of LDHIV (P = 0.0006, OR = 0.21; P = 0.01, OR = 0.18; P = 0.0002, OR = 0.40). When compared to patients without HIVLD from healthy controls, the ApoE 4/4 genotype, 2 and 4 alleles, were linked to a reduced risk of developing HIVLD (P = 0.0009, OR = 0.14; P = 0.0001, OR = 0.17; P = 0.00001, OR = 0.39). When comparing impaired to normal cholesterol levels in patients without HIVLD, the ApoE 3/4 genotype was linked with the increased risk of impaired cholesterol levels (P = 0.02, OR = 3.37). When comparing impaired and normal glucose levels in patients without HIVLD, the ApoE 4/4 genotype was associated to an elevated risk of impaired glucose levels (P = 0.03, OR = 8.27). In multivariate analysis, independent impaired cholesterol, LDL, and glucose levels were associated with a higher risk of lipodystrophy severity (P = 0.04, OR = 2.33; P = 0.001, OR = 4.05; P = 0.05, OR = 2.63). ApoE expression was up-regulated in LDHIV with a fold change value of 4.02 compared to those without HIVLD. ApoE protein level was found to be higher in patients of the HIVLD group (3.01 mg/dL) compared to those without HIVLD group (2.83 mg/dL). In conclusion, individuals with ApoE allele 2 were at higher risk for HIV-1 acquisition and severity of HIVLD, whereas those with ApoE allele 4 were at reduced HIVLD severity and development risk. It’s possible that ApoE’s increased level and its overexpression are related to the ApoE allele 2 in HIVLD patients. The development of LDHIV may be facilitated by the APOE 3/4 and 4/4 genotypes as well as abnormal glucose and cholesterol levels.

The impact of sex on HIV immunopathogenesis and therapeutic interventions.

Globally, the majority of people living with HIV are women or girls, but they have been a minority of participants in clinical trials and observational studies of HIV. Despite this underrepresentation, differences in the pathogenesis of HIV have been observed between men and women, with contributions from both gender- and sex-based factors. These include differences in the risk of HIV acquisition, in viral load set point and immune activation in responses to viremia, and differences in HIV reservoir maintenance. These differences obligate adequate study in both males and females in order to optimize treatments, but also provide a powerful leverage point for delineating the mechanisms of HIV pathogenesis. The shifts in exposure to sex steroid hormones across a lifespan introduce additional complexity, which again can be used to focus on either genetic or hormonal influences as the driver of an outcome. In this Review, we discuss consistent and reproducible differences by sex across the spectrum of HIV, from acquisition through pathogenesis, treatment, and cure, and explore potential mechanisms and gaps in knowledge.

Site-based and Digital Cohort Participation Among Transgender Women in the Eastern and Southern USA: Findings from the LITE Study.

Transgender women (TW) are highly burdened by HIV. There is increasing interest in digital (i.e., through internet-based interfaces) HIV research; yet few studies have assessed potential biases of digital compared to site-based data collection. This study examined differences in characteristics between TW participating via site-based versus digital-only modes in an HIV incidence cohort. Between March 2018-Aug 2020, a multisite cohort of 1,312 adult TW in the eastern and southern USA was enrolled in site-based and exclusively digital modes. We evaluated differences in baseline demographics, socio-structural vulnerabilities, healthcare access, gender affirmation, mental health, stigma, social support, and HIV acquisition risk comparing site-based vs digital modes using chi square tests and Poisson regression modeling with robust standard errors. The overall median age was 28 (interquartile range=23-35) years and over half identified as people of color (15% Black, 13% Multiracial, 12% Another Race, 18% Latina/e/x). A higher proportion of site-based (vs. digital mode) participants resided in the Northeast, were younger, identified as people of color, experienced socio-structural vulnerabilities, had a regular healthcare provider, received medical gender affirmation, endorsed mental health symptoms and stigma, reported HIV acquisition risk but also greater experience with biomedical HIV prevention (pre-exposure and post-exposure prophylaxis), and had larger social networks (all p<0.05). Site-based and digital approaches enrolled TW with different demographics, life experiences, and HIV acquisition risks. A hybrid cohort model may achieve a more diverse and potentially representative sample of TW than either site-based or online cohorts alone for HIV research.

Development and calibration of a mathematical model of HIV outcomes among Rwandan adults: informing equitable achievement of targets in Rwanda.

We developed and calibrated the Central Africa-International epidemiology Databases to Evaluate AIDS (CA-IeDEA) HIV policy model to inform equitable achievement of global goals, overall and across sub-populations, in Rwanda. We created a deterministic dynamic model to project adult HIV epidemic and care continuum outcomes, overall and for 25 subpopulations (age group, sex, HIV acquisition risk, urbanicity). Data came from the Rwanda cohort of CA-IeDEA, 2004-2020; Rwanda Demographic and Health Surveys, 2005, 2010, 2015; Rwanda Population-based HIV Impact Assessment, 2019; and the literature and reports. We calibrated the model to 47 targets by selecting the 50 best-fitting parameter sets among 20,000 simulations. Calibration targets reflected epidemic (HIV prevalence, incidence), global goals (percentage on antiretroviral therapy (ART) among diagnosed, percentage virally suppressed among on ART) and other (number on ART, percentage virally suppressed) indicators, overall and by sex. Best-fitting sets minimized the summed absolute value of the percentage deviation (AVPD) between model projections and calibration targets. Good model performance was mean AVPD ≤5% across the 50 best-fitting sets and/or projections within the target confidence intervals; acceptable was mean AVPD >5% and ≤15%. Across indicators, 1,841 of 2,350 (78.3%) model projections were a good or acceptable fit to calibration targets. For HIV epidemic indicators, 256 of 300 (85.3%) projections were a good fit to targets, with the model performing better for women (83.3% a good fit) than for men (71.7% a good fit). For global goals indicators, 96 of 100 (96.0%) projections were a good fit; model performance was similar for women and men. For other indicators, 653 of 950 (68.7%) projections were a good or acceptable fit. Fit was better for women than for men (percentage virally suppressed only) and when restricting targets for number on ART to 2013 and beyond. The CA-IeDEA HIV policy model fits historical data and can inform policy solutions for equitably achieving global goals to end the HIV epidemic in Rwanda. High-quality, unbiased population-based data, as well as novel approaches that account for calibration target quality, are critical to ongoing use of mathematical models for programmatic planning.

Sexually transmitted infections and bacterial vaginosis among adolescent girls and young women in the early postpartum period: a cross-sectional study

BackgroundUniversal antiretroviral treatment (ART) for pregnant women has reduced mother-to-child transmission risk significantly. However, not all women on ART are virally suppressed during pregnancy and lactation. In addition to poor adherence to ART, co-infections particularly other sexually transmitted infections (STIs) are known to increase the risk of HIV acquisition and HIV transmission. While the prevalence of STIs during pregnancy has been well studied, the prevalence of STIs in the postpartum period and its association with HIV viral suppression are underreported.MethodsIn this cross-sectional study, we determined the prevalence of STIs among adolescent girls and young women (AGYW) living with HIV (WLHIV) and without HIV (WNLHIV) at their 6–14 week postnatal clinic visit in a high HIV prevalence district in South Africa. All women were examined for STI-related symptoms and had vaginal swabs collected and stored for later STI testing. Vaginal swabs were tested for Trichomonas vaginalis (T.vaginalis), Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoea) and herpes simplex virus-2 (HSV-2) using PCR. All women were tested for bacterial vaginosis (BV) using the Nugent scoring criteria. WLHIV had a blood sample collected for HIV viral load, Hepatitis B and syphilis.ResultsIncluded in this analysis were 82 WLHIV and 102 WNLHIV. Between 6 and 14 weeks postpartum, 40 (21.7%) AGYW tested positive for any STI and among these 15 (37.5%) were symptomatic and received empirical treatment. C. trachomatis was most commonly detected (10.9%), followed by HSV-2 (7.7%), T. vaginalis (3.8%) and N. gonorrhoea (1.6%). WLHIV were more likely to test positive for an STI (OR 2.0; 0.96–3.96) and BV (OR 4.2; 95%CI 2.1–8.1) compared to WNLHIV. Among WLHIV on ART, 70.5% had an undetectable plasma viral load (PVL) and 20.5% had a PVL > 1000 copies/ml. Testing positive for any STI or BV at the postpartum visit was not associated with PVL > 1000 copies/ml (OR 1.33; 95%CI 0.38–4.64).ConclusionWe report a high prevalence of largely asymptomatic STIs and BV in the early postpartum period and STIs in WLHIV were not associated with unsuppressed PVL.The high STI positivity rate among WNLHIV has implications for HIV risk during the postpartum period, and subsequently breastfeeding transmission.

A risk-differentiated, community-led intervention to strengthen uptake and engagement with HIV prevention and care cascades among female sex workers in Zimbabwe (AMETHIST): a cluster randomised trial

Female sex workers remain disproportionately affected by HIV. The aim of this study was to determine the effect of risk-differentiated, peer-led support for female sex workers in Zimbabwe on the risk of HIV acquisition and HIV transmission from sex among female sex workers. In this cluster randomised, open-label, controlled study, 22 clinics dedicated to female sex workers co-located in government health facilities throughout Zimbabwe were allocated (1:1, through restricted randomisation) to usual care or AMETHIST intervention. Usual care comprised HIV testing, pre-exposure prophylaxis (PrEP), referral to government antiretroviral therapy (ART) services, contraception, condoms, syndromic management of sexually transmitted infections, health education, legal advice, and peer support. AMETHIST added peer-led microplanning tailored to individuals' risk and participatory self-help groups. All cisgender women (aged >18 years) who had sold sex within the past 30 days and lived or worked within trial cluster areas were eligible. Intervention status was not masked to programme implementers but was masked to survey teams and laboratory staff. After 28 months, a respondent-driven sampling (RDS) survey was done in the female sex worker population around each clinic, which measured the primary outcome, the combined proportion of female sex workers in the surveyed population at risk of transmitting HIV (ie, were HIV positive, not virally suppressed, and not consistently using condoms) or at risk of acquiring HIV (ie, were HIV negative and not consistently using condoms or PrEP). We report prespecified analyses of the disaggregated proportions of female sex workers in the surveyed population at risk of either transmission or acquisition of HIV. Analyses were prespecified, RDS-weighted, and age-adjusted. This trial is registered with the Pan African Clinical Trials Registry, PACTR202007818077777. The AMETHIST intervention was started on May 15, 2019, and data were collected from June 1, 2019, until Dec 13, 2021. The RDS survey was done from Oct 18 to Dec 13, 2021, with 2137 women included in the usual care group (11 clusters) and 2131 in the AMETHIST intervention group (11 clusters) after excluding survey seeds (n=132) and women with missing key data (n=44). 1973 (46·2%) of the 4268 female sex workers surveyed were living with HIV; of these, 863 (93·5%; RDS-adjusted) of 931 women in the intervention group and 927 (88·8%) of 1042 in the usual care group were virologically suppressed. 287 (22·4%) of 1200 HIV-negative women in the intervention group and 194 (15·7%) of 1096 in the usual care group reported currently taking PrEP, of whom only two (0·4%) of 569 had protective tenofovir diphosphate concentrations in dried blood spots (>700 fmol/dried blood punch). There was no effect of the intervention on the primary endpoint of risk of both HIV transmission and acquisition (intervention group n=1156/2131, RDS-adjusted proportion 55·3%; usual care group n=1104/2137, RDS-adjusted proportion 52·7%; age-adjusted risk difference -0·9%, 95% CI -5·7% to 3·9%, p=0·70). For the secondary outcomes, the proportion of women living with HIV at risk of transmission was low and significantly reduced in the intervention group (n=63/931, RDS-adjusted proportion 5·8%) compared with the usual care group (103/1041, 10·4%), with an age-adjusted risk difference of -5·5% (95% CI -8·2% to -2·9%, p=0·0003). Risk of acquisition among HIV-negative women was similar in the intervention (n=1093/1200, RDS-adjusted proportion 92·1%) and the usual care group (1001/1096, 92·2%), with an age-adjusted risk difference of -0·6% (95% CI -4·6 to 3·4, p=0·74). There was no overall benefit of the intervention on combined risk of transmission or acquisition. Viral load suppression in women living with HIV was high and appeared to be further improved by AMETHIST, suggesting potential for impressive uptake and adherence to ART in vulnerable and mobile populations. Sustaining treatment and reinvigorating prevention remain crucial. The Wellcome Trust and the Bill & Melinda Gates Foundation. For the Shona and Ndebele translations of the abstract see Supplementary Materials section.

Land-Based Retreats as a Method for Building Enabling Environments for HIV Prevention with Northern and Indigenous Adolescents in the Northwest Territories, Canada: Mixed-Methods Findings.

The Northwest Territories (NWT), Canada has high rates of sexually transmitted infections (STI) that elevate HIV acquisition risks. We conducted a mixed-methods study to explore the potential of land-based peer leader retreats (PLR) in building HIV prevention enabling environments among Northern and Indigenous youth in the NWT. PLRs are grounded in Indigenous principles and ways of knowing, acknowledging the land as a physical, spiritual, emotional, and intellectual being with the potential to facilitate (re)connection to culture, community, and self. We conducted one-week PLRs between 2016 and 2021 with adolescents aged 13-17 in the NWT. PLRs addressed HIV/STIs, safer sex, and gender equity. We conducted post-retreat focus groups (FGs) and pre/post-retreat surveys with youth participants (n = 353), and post-retreat FGs with PLR facilitators (n = 252). We applied thematic analysis to FGs and assessed pre/post-retreat changes in HIV/STI knowledge and safer sex efficacy (SSE) using paired sample t-tests. We assessed factors associated with post-test SSE and HIV/STI knowledge using multivariable linear regression. Youth participants (n = 353; mean age: 14.5, standard deviation [SD]: 1.3) were mostly Indigenous (71%) and women (66%). Participant narratives revealed PLRs enhanced technical communication (e.g., correct condom use). There were significant post-retreat HIV/STI knowledge increases; change score increases were lower for Indigenous participants. Qualitative narratives described how PLRs fostered transformative communication (e.g., sexual consent). There were significant post-retreat increases in SSE, and these were lower among men and sexually diverse (vs. heterosexual) participants. Land-based PLRs offer the potential to build technical and transformative communication to facilitate HIV prevention with youth in Canada's North.

Are violence, harmful alcohol/substance use and poor mental health associated with increased genital inflammation?: A longitudinal cohort study with HIV-negative female sex workers in Nairobi, Kenya.

Violence, alcohol use, substance use and poor mental health have been linked with increased HIV acquisition risk, and genital inflammation enhances HIV susceptibility. We examined whether past 6 month experience of these exposures was associated with increased genital inflammation, thereby providing a biological link between these exposures and HIV acquisition risk. The Maisha Fiti study was a longitudinal mixed-methods study of female sex workers in Nairobi, Kenya. Behavioural-biological surveys were conducted at baseline (June-December 2019) and endline (June 2020-March 2021). Analyses were restricted to HIV-negative women (n = 746). Women with raised levels of at least 5 of 9 genital inflammatory cytokines were defined as having genital inflammation. Multivariable logistic regression models were used to estimate (i) baseline associations between genital inflammation and violence, harmful alcohol/substance use, and poor mental health, and (ii) longitudinal associations between these exposures at different survey rounds, and genital inflammation at follow-up. Inflammation data was available for 711 of 746 (95.3%) women at baseline; 351 (50.1%) had genital inflammation, as did 247 (46.7%) at follow-up. At baseline, 67.8% of women had experienced physical and/or sexual violence in the past 6 months, 33.9% had harmful alcohol use, 26.4% had harmful substance use, 25.5% had moderate/severe depression/anxiety, and 13.9% had post-traumatic stress disorder. In adjusted analyses, there was no evidence that these exposures were associated cross-sectionally or longitudinally with genital inflammation. We report no associations between past 6 month experience of violence, harmful alcohol/substance use, or poor mental health, and immune parameters previously associated with HIV risk. This suggests that the well-described epidemiological associations between these exposures and HIV acquisition do not appear to be mediated by genital immune changes, or that any such changes are relatively short-lived. High prevalences of these exposures suggest an urgent need for sex-worker specific violence, alcohol/substance use and mental health interventions.

Non-HIV Vaccine-Induced Immune Responses as Potential Baseline Immunogenicity Predictors of ALVAC-HIV and AIDSVAX B/E-Induced Immune Responses.

Identifying correlations between immune responses elicited via HIV and non-HIV vaccines could aid the search for correlates of HIV protection and increase statistical power in HIV vaccine-efficacy trial designs. An exploratory objective of the HVTN 097 phase 1b trial was to assess whether immune responses [focusing on those supported as correlates of risk (CoR) of HIV acquisition] induced via the RV144 pox-prime HIV vaccine regimen correlated with those induced via tetanus toxoid (TT) and/or hepatitis B virus (HBV) vaccines. We measured TT-specific and HBV-specific IgG-binding antibody responses and TT-specific and HBV-specific CD4+ T-cell responses at multiple time points in HVTN 097 participants, and we assessed their correlations at peak time points with HIV vaccine (ALVAC-HIV and AIDSVAX B/E)-induced responses. Four correlations were significant [false discovery rate-adjusted p-value (FDR) ≤ 0.2]. Three of these four were with IgG-binding antibody responses to TT measured one month after TT receipt, with the strongest and most significant correlation [rho = 0.368 (95% CI: 0.096, 0.588; p = 0.008; FDR = 0.137)] being with IgG-binding antibody responses to MN gp120 gDneg (B protein boost) measured two weeks after the second ALVAC-HIV and AIDSVAX B/E boost. The fourth significant correlation [(rho = 0.361; 95% CI: 0.049, 0.609; p = 0.021; FDR = 0.137)] was between CD4+ T-cell responses to a hepatitis B surface antigen peptide pool, measured 2 weeks after the third HBV vaccination, and IgG-binding antibody responses to gp70BCaseAV1V2 (B V1V2 immune correlate), measured two weeks after the second ALVAC-HIV and AIDSVAX B/E boost. These moderate correlations imply that either vaccine, TT or HBV, could potentially provide a moderately useful immunogenicity predictor for the ALVAC-HIV and AIDSVAX B/E HIV vaccine regimen.

Coinfections increase the risk of HIV acquisition, AIDS progression, and therapy and prophylaxis failure: a review

Coinfections increase the risk of HIV acquisition, AIDS progression, and therapy and prophylaxis failure: a review

Intersecting Stigma and the HIV Care Cascade: Qualitative Insights from Sex Workers, Men who have Sex with Men, and Transgender Women Living with HIV in Jamaica.

In Jamaica, stigma experiences of sex workers (SW), gay men and other men who have sex with men (MSM), and transgender women living with HIV remain understudied. To address this gap, we explored experiences of stigma and linkages with the HIV care cascade among key populations living with HIV in Jamaica, including cisgender women SW, MSM, and transgender women. This qualitative study involved n = 9 focus groups (FG), n = 1 FG per population living with HIV (SW, MSM, transgender women) in each of three sites (Kingston, St. Ann, Montego Bay). We also conducted key informant (KI) interviews. We applied thematic analysis informed by the Health Stigma and Discrimination (HSD) Framework. FG participants (n = 67) included SW (n = 18), MSM (n = 28), and trans women (n = 21); we interviewed n = 10 KI (n = 5 cisgender women, n = 5 cisgender men). Participant discussions revealed that stigma drivers included low HIV treatment literacy, notably misinformation about antiretroviral therapy (ART) benefits and HIV acquisition risks, and a lack of legal protection from discrimination. Stigma targets health (HIV) and intersecting social identities (sex work, LGBTQ identities, gender non-conformity, low socio-economic status). Stigma manifestations included enacted stigma in communities and families, and internalized stigma-including lateral violence. HIV care cascade impacts included reduced and/or delayed HIV care engagement and ART adherence challenges/disruptions. Participants discussed strategies to live positively with HIV, including ART adherence as stigma resistance; social support and solidarity; and accessing affirming institutional support. In addition to addressing intersecting stigma, future research and programing should bolster multi-level stigma-resistance strategies to live positively with HIV.

Willingness to Use Long-acting Injectable Pre-exposure Prophylaxis Among Key Populations at a Large Hiv Prevention Clinic in Kampala, Uganda: a Cross-sectional Study.

Long-acting injectable (LAI)-PrEP provides better protection against HIV compared to oral PrEP, which requires taking a daily pill. Our study aimed to assess knowledge about oral and LAI-PrEP and identify factors associated with willingness to use LAI-PrEP among key populations (KP) in Uganda. We conducted a cross-sectional study at the Most at Risk Populations Initiative (MARPI) clinic between November and December 2021. Participants were recruited through convenience sampling and interviewed using a structured questionnaire by trained interviewers. Participants were categorised into three groups based on their oral PrEP use: those who had not yet initiated PrEP, those who had discontinued oral PrEP, and those currently on oral PrEP. Modified Poisson regression analysis was performed to determine factors associated with the participant's willingness to use LAI-PrEP. Data was analysed using STATA 14 software. Of the 234 participants, 135 (56.7%) were female, 82.5% knew about LAI-PrEP, and 67.5% were willing to use it. The mean age was 28.7 years (standard deviation [SD] 5.8). Willingness to use LAI-PrEP was less likely among divorced, widowed, or separated individuals than those in relationships (adjusted prevalence ratio [aPR] 0.65, 95% CI: 0.43-0.98). Relative to current oral PrEP users, willingness to use LAI-PrEP was similar among those who discontinued oral PrEP (aPR 1.39, 95% CI: 0.92-2.11) and those who had not yet initiated PrEP but were at risk for HIV (aPR 1.26, 95% CI: 0.83-1.89). In this cross-sectional analysis of diverse members of key populations in Uganda, previous or non-use of oral PrEP was not associated with willingness to use LAI-PrEP relative to current users. Future studies should investigate effective methods for promoting the uptake of long-acting PrEP formulations among populations at high risk of HIV acquisition.

Evaluation of person-centered interventions to eliminate perinatal HIV transmission in Kisumu County, Kenya: A repeated cross-sectional study using aggregated registry data.

Following a decline in perinatal HIV transmission from 20% to 10% between 2010 and 2017 in Kenya, rates have since plateaued with an estimated 8% transmission rate in 2021. Between October 2016 and September 2021, Family AIDS Care & Education Services (FACES) supported HIV care and treatment services across 61 facilities in Kisumu County, Kenya with an emphasis on service strengthening for pregnant and postpartum women living with HIV to reduce perinatal HIV transmission. This included rigorous implementation of national HIV guidelines and implementation of 3 locally adapted evidence-based interventions targeted to the unique needs of women and their infants. We examined whether these person-centered program enhancements were associated with changes in perinatal HIV transmission at FACES-supported sites over time. We conducted a repeated cross-sectional study of annually aggregated routinely collected documentation of perinatal HIV transmission risk through the end of breastfeeding at FACES-supported facilities between October 2016 and September 2021. Data included 12,599 women living with HIV with baseline antenatal care metrics, and, a separate data set of 11,879 mother-infant pairs who were followed from birth through the end of breastfeeding (overlapping with those in antenatal care 2 years prior). FACES implemented 3 interventions for pregnant and postpartum women living with HIV in 2019: (1) high-risk clinics; (2) case management; and (3) a mobile app to support treatment engagement. Our primary outcome was infant HIV acquisition by the end of breastfeeding (18 to 24 months). We compared infant HIV acquisition risk in the final year of the FACES program (2021) to the year before intervention scale-up and following implementation of the "Treat All" policy (2018). Mother-infant pair loss to follow-up was a secondary outcome. Program data were aggregated by year and site, thus in multivariable regression, we adjusted for site-level characteristics, including facility type, urban versus rural, number of women with HIV in antenatal care each year, and the proportion among them under 25 years of age. Between October 2016 and September 2021, 81,172 pregnant women received HIV testing at the initiation of antenatal care, among whom 12,599 (15.5%) were living with HIV, with little variation in HIV prevalence over time. The risk of infant HIV acquisition by 24 months of age declined from 4.9% (101/2,072) in 2018 to 2.2% (48/2,156) in 2021 (adjusted risk difference -2.6% [95% confidence interval (CI): -3.7, -1.6]; p < 0.001). Loss to follow-up declined from 9.9% (253/2,556) in 2018 to 2.5% (59/2,393) in 2021 (risk difference -7.5% [95% CI: -8.8, -6.2]; p < 0.001). During the same period, UNAIDS estimated rates of perinatal transmission in the broader Nyanza region and in Kenya as a whole did not decline. The main limitation of this study is that we lacked a comparable control group. These findings suggest that implementation of person-centered interventions was associated with significant declines in perinatal HIV transmission and loss to follow-up of pregnant and postpartum women.