Sexual and reproductive health among forcibly displaced persons in urban environments in low and middle-income countries: scoping review findings.

BACKGROUND: Most forcibly displaced persons are hosted in low- and middle-income countries (LMIC). There is a growing urbanization of forcibly displaced persons, whereby most refugees and nearly half of internally displaced persons live in urban areas. This scoping review assesses the sexual and reproductive health (SRH) needs, outcomes, and priorities among forcibly displaced persons living in urban LMIC. METHODS: Following The Joanna Briggs Institute scoping review methodology we searched eight databases for literature published between 1998 and 2023 on SRH needs among urban refugees in LMIC. SHR was operationalized as any dimension of sexual health (comprehensive sexuality education [CSE]; sexual and gender based violence [GBV]; HIV and STI prevention and control; sexual function and psychosexual counseling) and/or reproductive health (antental, intrapartum, and postnatal care; contraception; fertility care; safe abortion care). Searches included peer-reviewed and grey literature studies across quantitative, qualitative, or mixed-methods designs. FINDINGS: The review included 92 studies spanning 100 countries: 55 peer-reviewed publications and 37 grey literature reports. Most peer-reviewed articles (n = 38) discussed sexual health domains including: GBV (n = 23); HIV/STI (n = 19); and CSE (n = 12). Over one-third (n = 20) discussed reproductive health, including: antenatal, intrapartum and postnatal care (n = 13); contraception (n = 13); fertility (n = 1); and safe abortion (n = 1). Eight included both reproductive and sexual health. Most grey literature (n = 29) examined GBV vulnerabilities. Themes across studies revealed social-ecological barriers to realizing optimal SRH and accessing SRH services, including factors spanning structural (e.g., livelihood loss), health institution (e.g., lack of health insurance), community (e.g., reduced social support), interpersonal (e.g., gender inequitable relationships), and intrapersonal (e.g., low literacy) levels. CONCLUSIONS: This review identified displacement processes, resource insecurities, and multiple forms of stigma as factors contributing to poor SRH outcomes, as well as producing SRH access barriers for forcibly displaced individuals in urban LMIC. Findings have implications for mobilizing innovative approaches such as self-care strategies for SRH (e.g., HIV self-testing) to address these gaps. Regions such as Africa, Latin America, and the Caribbean are underrepresented in research in this review. Our findings can guide SRH providers, policymakers, and researchers to develop programming to address the diverse SRH needs of urban forcibly displaced persons in LMIC. Most forcibly displaced individuals live in low- and middle-income countries (LMICs), with a significant number residing in urban areas. This scoping review examines the sexual and reproductive health (SRH) outcomes of forcibly displaced individuals in urban LMICs. We searched eight databases for relevant literature published between 1998 and 2023. Inclusion criteria encompassed peer-reviewed articles and grey literature. SRH was defined to include various dimensions of sexual health (comprehensive sexuality education; sexual and gender-based violence; HIV/ STI prevention; sexual function, and psychosexual counseling) and reproductive health (antenatal, intrapartum, and postnatal care; contraception; fertility care; and safe abortion care). We included 90 documents (53 peer-reviewed articles, 37 grey literature reports) spanning 100 countries. Most peer-reviewed articles addressed sexual health and approximately one-third centered reproductive health. The grey literature primarily explored sexual and gender-based violence vulnerabilities. Identified SRH barriers encompassed challenges across structural (livelihood loss), health institution (lack of insurance), community (reduced social support), interpersonal (gender inequities), and individual (low literacy) levels. Findings underscore gaps in addressing SRH needs among urban refugees in LMICs specifically regarding sexual function, fertility care, and safe abortion, as well as regional knowledge gaps regarding urban refugees in Africa, Latin America, and the Caribbean. Self-care strategies for SRH (e.g., HIV self-testing, long-acting self-injectable contraception, abortion self-management) hold significant promise to address SRH barriers experienced by urban refugees and warrant further exploration with this population. Urgent research efforts are necessary to bridge these knowledge gaps and develop tailored interventions aimed at supporting urban refugees in LMICs.

HIV Infection Modifies the Role of Prior Treponema pallidum Infection in the Clinical Presentation of Early Syphilis among Adult Patients from STI Clinics in Peru.

BACKGROUND: We aim to compare the clinical presentations (symptomatic vs asymptomatic) with prior Treponema pallidum infection status (first infection vs reinfection) among people with early syphilis. METHODS: We used data from PICASSO, a cohort study in Peru, that enrolled people with active syphilis from May 2019 to August 2021. Study participants had early syphilis and a prior syphilis serologic test result within the prior 12 months to determine prior T. pallidum infection status. We calculated prevalence ratios of symptomatic clinical presentation (primary or secondary syphilis) by prior T. pallidum infection status, stratified by HIV infection status. Additionally, we explored the association of prior T. pallidum infection status and lesion presentation, stratified by primary and secondary syphilis cases, using the Fisher's exact test. RESULTS: We include 84 T. pallidum reinfection cases and 61 first infection cases. We found increased frequency of symptomatic clinical presentation among first-infection cases (39% vs 20%, PR = 1.94, p = 0.014). This association was stronger among persons living without HIV infection (38% vs 7%, aPR = 6.63, p = 0.001) in comparison to those living with HIV infection (45% vs 34%, aPR = 1.38, p = 0.458). Among secondary syphilis cases, more participants from the reinfection group reported that their lesions improved one week after treatment (100% vs 29%, p = 0.045) compared to those with a first infection. Among the primary syphilis cases, all participants reported that their lesions improved one week after treatment. CONCLUSION: Prior syphilis was associated with decreased prevalence of symptomatic reinfection, especially among persons not living with HIV infection.

Does genital herpes symptom history predict herpes simplex virus type 2 antibody positivity?

BACKGROUND: Sexually transmitted infections (STIs) associated with genital ulcer disease due to herpes simplex virus-2 (HSV-2) are a prominent cause of morbidity and mortality. Serologic screening for HSV-2 is recommended only for individuals with genital herpes symptom history. However, no validated symptom screening tool currently exists. METHODS: Currently asymptomatic adults presenting for routine care at STI clinics in Lima, Peru completed a survey of prior genital herpes symptoms and received HSV-2 serological testing with the Euroimmun Anti-HSV-2 (gG2) ELISA IgG (Lubeck, Germany). A sub-sample of indeterminate results were sent for Western blot confirmatory testing. We assessed associations between past symptoms and anti-HSV-2 positivity and corrected the HSV-2 prevalence by re-classifying indeterminates per Western Blot results. RESULTS: We enrolled 131 participants between July and October 2022. HSV-2 antibody test results found 21.4% positive, 41.2% indeterminate, and 37.4% negative. Excluding indeterminate results, 36.4% were positive. Of participants with no prior symptoms 31.2% tested positive, compared to 35.7% with one prior symptom, 50.0% with 2, and 50.0% with 3+ prior symptoms. Among the sub-sample of indeterminates, 92.6% were confirmed positive by Western Blot, bringing the total estimated proportion of participants with HSV-2 antibodies to 59.5%. Either based on the original classification of HSV-2 antibody status or after incorporation of confirmatory testing results, there was no significant association between symptom history and HSV-2 antibody positivity. CONCLUSIONS: With currently available tests, recommendations to screen individuals based on genital herpes symptom history may not be useful. More discriminatory symptom screening tools or HSV-2 antibody tests with better performance are needed.

Evaluation of a minimal array of Treponema pallidum antigens as biomarkers for syphilis diagnosis, infection staging, and response to treatment.

IMPORTANCE: This manuscript explores the host humoral response to selected antigens of the syphilis agent during infection to evaluate their potential use as diagnostic tests and markers for treatment.

Recent HIV infection and annualized HIV incidence rates among sexual and gender minorities in Brazil and Peru (ImPrEP seroincidence study): a cross-sectional, multicenter study.

Background: HIV incidence estimation is critical for monitoring the HIV epidemic dynamics and the effectiveness of public health prevention interventions. We aimed to identify sexual and gender minorities (SGM) with recent HIV infections, factors associated with recent HIV infection, and to estimate annualised HIV incidence rates. Methods: Cross-sectional multicentre study in HIV testing services in Brazil and Peru (15 cities). Inclusion criteria: 18+ years, SGM assigned male at birth, not using pre-/post-exposure prophylaxis. We identified recent HIV infection using the Maxim HIV-1 LAg-Avidity EIA assay as part of a recent infection testing algorithm (RITA). Annualized HIV incidence was calculated using the UNAIDS/WHO incidence estimator tool. Multivariable logistic regression models were used to estimate factors associated with recent HIV infection. Trial registration: NCT05674682. Findings: From 31-Jan-2021 to 29-May-2022, 6899 individuals participated [Brazil: 4586 (66.5%); Peru: 2313 (33.5%)]; 5946 (86.2%) cisgender men, 751 (10.9%) transgender women and 202 (2.9%) non-binary/gender diverse. Median age was 27 (IQR: 23-34) years. HIV prevalence was 11.4% (N = 784/6899); 137 (2.0%) SGM were identified with recent HIV infection. The overall annualized HIV incidence rate was 3.88% (95% CI: 2.86-4.87); Brazil: 2.62% (95% CI: 1.78-3.43); Peru: 6.69% (95% CI: 4.62-8.69). Participants aged 18-24 years had higher odds of recent HIV infection compared to those aged 30+ years in both countries. Interpretation: Our results highlight the significant burden of HIV epidemic among SGM in large urban centres of Brazil and Peru. Public health policies and interventions to increase access to effective HIV prevention methods such as PrEP are urgently needed in Latin America. Funding: Unitaid, WHO (Switzerland), Ministry of Health from Brazil and Peru.

Molecular Characterization of Genital and Extragenital Lesions With the PlexPCR VHS Assay in Patients Diagnosed With Syphilis.

Background: Syphilis diagnosis relies on immunologic markers and clinical protocols. However, syphilitic lesions can be confused with other genital ulcer diseases. Methods: Using a PlexPCR VHS assay, we analyzed lesion DNA samples from 87 individuals who were clinically diagnosed with early syphilis infection and had at least 1 positive serologic test result. DNA was detected by the PlexPCR VHS multiplex assay and ß-globin genes. Results: Among the participants, 99% (86/87) had a positive rapid treponemal test result. DNA was successfully detected in 91% (79/87) of the lesion samples. PlexPCR VHS identified 5 herpes simplex virus (HSV)/Treponema pallidum coinfections (2 HSV-1 and 3 HSV-2), only T pallidum DNA in 62% (49/79), and only HSV-2 in 12.7% (10/79). While 19% (15/79) were negative for all pathogens, none were varicella zoster virus positive. The PlexPCR VHS had 68.4% agreement with the clinical diagnosis. Conclusions: Since the PlexPCR VHS detects multiple organisms simultaneously, it can help to confirm actual syphilis and identify other pathogen coinfections or the pathogen causing the ulcer.

Contributing factors for self-reported HIV in male Peruvian inmates: results of the 2016 prison census.

Introduction: Worldwide, prisons are high-risk settings for the transmission of infectious diseases such as HIV. There is a need to understand the health conditions of prisoners to improve and implement timely strategies for HIV diagnosis and control. Hence, we aimed to identify factors associated with self-reported HIV (srHIV) among Peruvian inmates. Methods: This study is a secondary data analysis of the First Peruvian Prison Census conducted in 2016. We estimated the prevalence of srHIV in prisoners who were male at birth and the association of srHIV with other social conditions, criminal records, and prevalent health conditions. Nested models identified a multivariable parsimonious model for factors associated with srHIV and yielding prevalence ratios adjusted by the included parameters. Results: The census surveyed 71,087 male inmates of whom 0.4% reported srHIV (n = 305), and 82% of whom were receiving antiretroviral treatment (n = 220). In our final multivariable model, srHIV was independently associated with age between 36 and 55 years old vs. >55 years old [parsimonious prevalence ratio (pPR) = 1.98, 95% CI, 0.96-4.08], having a stable partner out of prison (pPR = 1.64, 95% CI, 1.24-2.19), being homosexual (pPR = 4.16, 95% CI, 2.50-6.90), self-report of prevalent tuberculosis co-infection (pPR = 2.55, 95% CI, 1.82-3.58), self-report of prevalent sexually transmitted infections (pPR = 34.49, 95% CI, 24.94-47.70), and self-report of prevalent illicit drug use 30 days before the survey (pPR = 1.91, 95% CI, 1.43-2.56). Conclusion: Self-reported HIV is associated with multiple social, health and prison risks among Peruvian inmates. Deeply understanding these factors would help to design HIV prevention and control strategies in Peruvian prisons.

Safety of Linezolid During Pregnancy.

ABSTRACT: With growing maternal and congenital syphilis epidemics and shortages of benzathine penicillin, alternative syphilis treatments are needed. Linezolid has shown efficacy against syphilis in animal models. This review found no teratogenic effects. Some adverse effects were seen in animals, but none were reported in a small number of human studies.

PrEP policy implementation gaps and opportunities in Latin America and the Caribbean: a scoping review.

Background: Pre-exposure prophylaxis (PrEP) is an important tool for HIV prevention in Latin America and the Caribbean (LAC). Yet, little is known about the PrEP policies landscape in the region. Addressing this gap, this scoping review assessed current PrEP policies throughout LAC to better understand existing PrEP implementation gaps and identify opportunities to improve access. Methods: We conducted a scoping review, using a modified PRISMA extension, through 28 July 2022, to identify country-level PrEP policies. Data were collected in English, Spanish, French, and Portuguese utilizing online platforms for screening and data extraction (Google Forms, Zotero, and Excel). Extracted data were divided by data source, including country-level government policies, gray literature, and peer-reviewed literature, with at least one full-text reviewer and data extractor per publication. An iterative summative content analysis was performed to compare and interpret themes across phases and data sources. Results: Of the 33 countries in LAC, 22 (67%) had policies approving daily oral PrEP for HIV prevention, which outlined specific key populations, including men who have sex with men, transgender women, sex workers, and serodiscordant couples. Generic tenofovir disoproxil fumarate/emtricitabine has been approved in 15 of the 33 countries, and 13 of the 33 countries have incorporated PrEP into their public health system. No countries were found to have approved cabotegravir. Costing data were reported by only one country, Ecuador, in its national health ministry guidelines. Findings also document a lag between the media/gray-literature announcement of PrEP and implementation of policies. Conclusion: Findings underscore significant advances in PrEP policies in the region and signal opportunities for greater PrEP implementation. Since 2017, an increasing number of countries have begun to provide PrEP to communities at heightened need, although significant gaps remain. Policy approval is a key step to further increasing access to PrEP in LAC, necessary to reduce the burden of HIV in LAC, specifically among marginalized populations.

Preferences for PrEP modalities among gay, bisexual, and other men who have sex with men from Brazil, Mexico, and Peru: a cross-sectional study.

Background: Pre-exposure prophylaxis (PrEP) scale-up is urgent to reduce new HIV cases among gay, bisexual, and other men who have sex with men (MSM) in Latin America. Different PrEP modalities may increase PrEP uptake and adherence, especially among young MSM. Objectives: To assess preferences for PrEP modalities among MSM from Brazil, Mexico, and Peru. Design: Cross-sectional web-based study (March-May 2018) targeting MSM through advertisements on Grindr, Hornet, and Facebook. We included MSM aged ⩾ 18 years and who reported HIV-negative status. Methods: We assessed preferences for PrEP modalities with the following question: 'Considering that all following PrEP modalities were available, which one would you prefer considering a scale from 1 to 3 (1 = most preferred): daily oral PrEP, event-driven PrEP (ED-PrEP), and long-acting injectable PrEP'. We assessed factors associated with each most preferred PrEP modality per country using multivariable logistic regression models. Results: A total of 19,457 MSM completed the questionnaire (Brazil: 58%; Mexico: 31%; Peru: 11%); median age was 28 years [interquartile range (IQR): 24-34]. Overall, injectable PrEP was the most preferred modality [42%; 95% confidence interval (CI): 41-43], followed by daily PrEP (35%; 95% CI: 34-35), and ED-PrEP (23%; 95% CI: 23-24). In multivariable models, preferring injectable PrEP was associated with PrEP awareness in all three countries, while PrEP eligibility only in Brazil. Preferring daily PrEP was associated with younger age and lower income in Brazil and Mexico, and lower education only in Brazil. The odds of preferring ED-PrEP were lower among MSM aware and eligible for PrEP in Brazil and Mexico. Conclusions: Long-acting injectable PrEP was the preferred PrEP modality among MSM in Brazil, Mexico, and Peru, especially those aware and eligible for PrEP. Public health interventions to increase PrEP modalities literacy and availability in Latin America are urgent especially among MSM of young age, lower income, and lower education.

Extra-genital Neisseria gonorrhoeae infections with genetic mutations conferring ciprofloxacin resistance among men who have sex with men and transgender women in Lima, Peru.

BACKGROUND: The increasing prevalence of drug-resistant Neisseria gonorrhoeae (NG) infections has caused great concern. Ciprofloxacin remains the empiric antimicrobial recommended to treat NG infections in Peru disregarding the susceptibility profile of circulating NG strains. We report the prevalence of individuals infected with NG strains presenting mutations in the gyrA gene that confers ciprofloxacin resistance. METHODS: We conducted a descriptive study assessing extragenital swab samples collected from a cohort of men who have sex with men and transgender women in Lima, Peru. Anal and pharyngeal NG positive swabs for Aptima Combo 2 assay (Hologic Inc., USA) were used for DNA extraction. We performed TaqMan real time PCR assays to detect a point mutation at codon Ser91 of the gyrase A (gyrA) gene. RESULTS: From 156 individuals who had at least one positive sample for NG reported by the Aptima assay, 80 individuals had at least one amplified DNA for the gyrA gene. We found that 67 of them (84.0%) were infected with a gyrA-mutated NG strain at the Ser91 codon. CONCLUSIONS: We report a high prevalence of gyrA mutation conferring ciprofloxacin resistance among individuals with extragenital NG infection. Empirical treatment of NG needs to be urgently updated in Peru in concordance with international guidelines.

HIV Risk Perception and Pre-Exposure Prophylaxis (PrEP) Awareness Among Transgender Women from Mexico.

This study aimed to identify factors associated with HIV risk perception among Mexican transgender women (TGW). This cross-sectional survey was conducted online and at a public HIV clinic in Mexico City. Participants were ≥ 18 years old, self-identified as TGW, and reported not living with HIV. They answered questions on sexual behavior, HIV risk perception, and pre-exposure prophylaxis (PrEP) awareness. We performed a multivariate logistic regression to accomplish the study's objective. One hundred ninety-one TGW completed the survey. High HIV risk perception was associated with > 5 sexual partners, condomless receptive anal sex, sex with a male partner(s) of unknown HIV status, and PrEP awareness. Although most TGW reported low HIV risk perception, over half had risk sexual behavior, reflecting inaccurate risk assessment. Future interventions to improve accurate risk perception among TGW should promote HIV transmission and prevention knowledge and increase PrEP awareness and uptake.

RESUMEN: Este estudio tuvo como objetivo identificar los factores asociados con la percepción de riesgo al VIH entre las mujeres trans (MT) mexicanas. El reclutamiento de esta encuesta transversal se realizó en línea y en una clínica pública de VIH en la Ciudad de México. Las participantes tenían ≥ 18 años, se autoidentificaron como MT y reportaron no vivir con VIH. Respondieron preguntas sobre su comportamiento sexual, percepción del riesgo al VIH y conocimiento de la profilaxis preexposición (PrEP). Se realizó un análisis de regresión logística multivariado para cumplir con el objetivo del estudio. Ciento noventa y uno participantes completaron la encuesta. La percepción de alto riesgo al VIH se asoció con > 5 parejas sexuales, sexo anal receptivo sin condón, sexo con una pareja masculina de estado serológico desconocido y conocimiento de la PrEP. Aunque la mayoría de las MT informaron baja percepción del riesgo al VIH, más de la mitad reportaron conductas sexuales de riesgo, lo que refleja una evaluación de riesgo inexacta. Futuras intervenciones para mejorar la percepción precisa del riesgo entre las MT deben centrarse en promover el conocimiento de transmisión y la prevención del VIH, así como aumentar el conocimiento y la aceptación de la PrEP.

Same-day initiation of oral pre-exposure prophylaxis among gay, bisexual, and other cisgender men who have sex with men and transgender women in Brazil, Mexico, and Peru (ImPrEP): a prospective, single-arm, open-label, multicentre implementation study.

BACKGROUND: Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru. METHODS: Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021. FINDINGS: From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18-24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20-2·14), participants aged 18-24 years (1·80, 1·49-2·18), and participants with primary education (2·18, 1·29-3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46-0·70), participants aged 18-24 years (0·52, 0·46-0·58), and those with primary education (0·60, 0·40-0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45-0·71), participants aged 18-24 years (0·56, 0·49-0·64), and those with secondary education (0·74, 0·68-0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70-1·03) and was higher for transgender women, participants from Peru, those aged 18-24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP. INTERPRETATION: Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP. FUNDING: Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny.

Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged ß-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.

Factors associated with long-term HIV pre-exposure prophylaxis engagement and adherence among transgender women in Brazil, Mexico and Peru: results from the ImPrEP study.

INTRODUCTION: The HIV epidemic continues to disproportionately impact Latin-American transgender women (TGW). We assessed factors associated with long-term pre-exposure prophylaxis (PrEP) engagement and adherence among TGW enrolled in the Implementation of PrEP (ImPrEP) study, the largest PrEP demonstration study in Latin America. METHODS: HIV-negative TGW aged ≥18 years reporting 1+eligibility criteria in the 6 months prior to enrolment (e.g. sex partner known to be living with HIV, condomless anal sex [CAS], transactional sex or having a sexually transmitted infection [STI]) who could safely take PrEP were enrolled. Follow-up visits were conducted at 4 weeks and then quarterly. We conducted logistic regression to identify factors associated with long-term PrEP engagement (3+ follow-up visits in 52 weeks) and complete self-reported adherence (no missed pills in the past 30 days) during follow-up. For both outcomes, we constructed multivariable models controlling for country, socio-demographics, sexual behaviour, substance use, STIs and self-reported adherence at 4 weeks (long-term engagement outcome only). RESULTS: From March 2018 to June 2021, ImPrEP screened 519 TGW, enrolled 494 (Brazil: 190, Mexico: 66 and Peru: 238) and followed them for 52 weeks. At baseline, 27.5% of TGW were aged 18-24 years, 67.8% were mixed-race and 31.6% had >secondary education. Most, 89.9% reported CAS, 61.9% had >10 sex partners and 71.9% reported transactional sex. HIV incidence was 1.82 cases per 100 person-years (95% confidence interval [CI]: 0.76-4.38). Almost half of TGW (48.6%) had long-term PrEP engagement, which was positively associated with reporting complete adherence at week 4 (aOR:2.94 [95%CI:1.88-4.63]) and was inversely associated with reporting CAS with unknown-HIV partner (aOR:0.52 [95%CI:0.34-0.81]), migration (aOR:0.54 [95%CI:0.34-0.84]), and being from Mexico (aOR:0.28 [95%CI:0.14-0.53]). Self-reported adherence was associated with TGW aged >34 (aOR:1.61 [95%CI:1.10-2.34]) compared to those aged 25-34 and those with >secondary education (aOR:1.55 [95%CI:1.10-2.19]) and was lower among TGW from Peru (aOR:0.29 [95%CI:0.21-0.41]) or reporting PrEP-related adverse effects (aOR:0.63 [95%CI:0.42-0.92]). CONCLUSIONS: Although TGW were willing to enrol in ImPrEP, long-term PrEP engagement and complete self-reported adherence were limited, and HIV incidence remained relatively high. A successful HIV prevention agenda should include trans-specific interventions supporting oral PrEP and exploring long-acting PrEP strategies for TGW.

Notes on syphilis vaccine development.

The quest for a syphilis vaccine to provide protection from infection or disease began not long after the isolation of the first Treponema pallidum subspecies pallidum (T. pallidum) strain in 1912. Yet, a practical and effective vaccine formulation continues to elude scientists. Over the last few years, however, efforts toward developing a syphilis vaccine have increased thanks to an improved understanding of the repertoire of T. pallidum outer membrane proteins (OMPs), which are the most likely syphilis vaccine candidates. More has been also learned about the molecular mechanisms behind pathogen persistence and immune evasion. Published vaccine formulations based on a subset of the pathogen's OMPs have conferred only partial protection upon challenge of immunized laboratory animals, primarily rabbits. Nonetheless, those experiments have improved our approach to the choice of immunization regimens, adjuvants, and vaccine target selection, although significant knowledge gaps remain. Herein, we provide a brief overview on current technologies and approaches employed in syphilis vaccinology, and possible future directions to develop a vaccine that could be pivotal to future syphilis control and elimination initiatives.

Laboratory Evaluation of the DPP Syphilis Screen & Confirm Assay.

Because syphilis is a public health concern, new strategies and tools for detecting active syphilis cases should be evaluated for future implementation. We assessed the laboratory performance of the DPP Syphilis Screen & Confirm rapid immunodiagnostic test (Chembio Diagnostics, Medford, NY, USA), using visual reading and the manufacturer's electronic test microreader, for detection of treponemal and nontreponemal antibodies in 383 fully characterized stored serum specimens. We used the Treponema pallidum particle agglutination (TPPA) test and rapid plasma reagin (RPR) test as reference tests for the DPP Syphilis Screen & Confirm assay treponemal and nontreponemal components, respectively. The sensitivity values for treponemal antibody detection by electronic reader and visual interpretation were 83.2% and 85.9%, respectively, with 100% specificity. For nontreponemal antibody detection, the sensitivity values were 65.7% and 69.0% and the specificity values were 88.7% and 89.4% for electronic reader and visual interpretation, respectively. There was excellent correlation between visual interpretation and the microreader for either component (kappa coefficient, 0.953). When restricting the analysis to RPR titers of ≥1:8, the sensitivity was 96.9% for either reading method; numerical microreader values showed good correlation with RPR titers (Spearman rho of 0.77). The DPP Syphilis Screen & Confirm assay showed good performance, compared to reference syphilis tests, using serum. Field evaluation studies should be done to validate its use for detection of active cases and for monitoring of treated syphilis patients. IMPORTANCE Syphilis remains a public health problem; therefore, health systems must incorporate screening tools that allow a rapid and accurate diagnosis to provide adequate treatment. The DPP Syphilis Screen & Confirm Assay simultaneously detects treponemal and nontreponemal antibodies, emerging as an alternative for identifying cases in situations in which there is no infrastructure to perform conventional syphilis testing, but it is necessary to generate evidence regarding the performance of this technology in various scenarios. We found that the test performs well, compared to TPPA and RPR tests, using stored samples from participants at high risk of acquiring syphilis. Additionally, when the Chembio microreader was incorporated, similar results are obtained by the device, compared to those reported by trained laboratory professionals, and correlated with the semiquantitative results of the RPR test. We think that the use of the DPP Syphilis Screen & Confirm Assay with the microreader might help in detecting active syphilis cases and perhaps in monitoring treatment responses in the field.

Awareness, knowledge, and attitudes related to HIV pre-exposure prophylaxis and other prevention strategies among physicians from Brazil and Mexico: cross-sectional web-based survey.

BACKGROUND: In order to end the HIV epidemic by 2030, combination HIV prevention including pre-exposure prophylaxis (PrEP) should be widely available, especially for the most vulnerable populations. In Latin America and the Caribbean (LAC), only 14 out of 46 countries have access to PrEP. In Brazil and Mexico, PrEP has been provided at no cost through the Public Health System since 2017 and 2021, respectively. Thus, HIV physicians' perspectives about PrEP and other prevention strategies may differ. This study aimed to compare awareness, knowledge, and attitudes related to PrEP and other prevention strategies among HIV physicians from Brazil and Mexico. METHODS: Cross-sectional, web-based survey targeting physicians who prescribe antiretrovirals from both countries. Participants answered questions on socio-demographic, medical experience, awareness, knowledge, and attitudes towards PrEP and other HIV prevention strategies. We stratified all variables per country and compared frequencies using Chi-square, Fisher exact, and Wilcoxon-Mann-Whitney tests, as appropriate. RESULTS: From January-October 2020, 481 HIV physicians were included: 339(70.5%) from Brazil, 276(57.4%) male, and median age was 43 years (IQR = 36-53). Awareness of PrEP did not differ between Brazil and Mexico (84.6%), while awareness of other prevention strategies, including post-exposure prophylaxis and new PrEP technologies, was higher in Brazil. More Brazilians perceived U=U as completely accurate compared to Mexicans (74.0% vs. 62.0%, P < .001). Willingness to prescribe PrEP was 74.2%, higher among Brazilians (78.2%, P = .01). Overall, participants had concerns about consistent access to PrEP medication and the risk of antiretroviral resistance in case of acute HIV infection or seroconversion. The main barriers reported were assumptions that users could have low PrEP knowledge (62.0%) or limited capacity for adherence (59.0%). Compared to Brazilians, Mexicans reported more concerns and barriers to PrEP prescription (all; P ≤ .05), except for consistent access to PrEP medication and the lack of professionals to prescribe PrEP (both; P ≤ .01). CONCLUSIONS: Although awareness of PrEP was similar in Brazil and Mexico, differences in knowledge and attitudes may reflect the availability and stage of PrEP implementation in these countries. Strengthening and increasing information on PrEP technologies and other HIV prevention strategies among HIV physicians could improve their comfort to prescribe these strategies and facilitate their scale-up in LAC.