Zipime-Weka-Schista study protocol: a longitudinal cohort study and economic evaluation of an integrated home-based approach for genital multipathogen screening in women, including female genital schistosomiasis, human papillomavirus, Trichomonas and HIV in Zambia.

INTRODUCTION: Multiplathogen home-based self-sampling offers an opportunity to increase access to screening and treatment in endemic settings with high coinfection prevalence of sexually transmitted (HIV, Trichomonas vaginalis (Tv), human papillomavirus (HPV)) and non-sexually transmitted pathogens (Schistosoma haematobium (Sh)). Chronic coinfections may lead to disability (female genital schistosomiasis) and death (cervical cancer). The Zipime-Weka-Schista (Do self-testing sister!) study aims to evaluate the validity, acceptability, uptake, impact and cost-effectiveness of multipathogen self-sampling for genital infections among women in Zambia. METHODS AND ANALYSIS: This is a longitudinal cohort study aiming to enrol 2500 non-pregnant, sexually active and non-menstruating women aged 15-50 years from two districts in Zambia with 2-year follow-up. During home visits, community health workers offer HIV and Tv self-testing and cervicovaginal self-swabs for (1) HPV by GeneXpert and, (2) Sh DNA detection by conventional (PCR)and isothermal (recombinase polymerase assay) molecular methods. Schistosoma ova and circulating anodic antigen are detected in urine. At a clinic follow-up, midwives perform the same procedures and obtain hand-held colposcopic images. High-risk HPV positive women are referred for a two-quadrant cervical biopsy according to age and HIV status. A cost-effectiveness analysis is conducted in parallel. ETHICS AND DISSEMINATION: The University of Zambia Biomedical Research Ethics Committee (UNZABREC) (reference: 1858-2021), the London School of Hygiene and Tropical Medicine (reference: 25258), Ministry of Health and local superintendents approved the study in September 2021.Written informed consent was obtained from all participants prior to enrolment. Identifiable data collected are stored securely and their confidentiality is protected in accordance with the Data Protection Act 1998.

Social norms that sustain transactional sex and associations with sexual health outcomes: A mixed-methods study in the Comarca Ngäbe-Buglé, a rural-Indigenous region of Panama.

The Comarca Ngäbe-Buglé (CNB), home to >200,000 Indigenous people, is one of the poorest regions in Panama. We describe transactional sex (TS) behaviours, normative beliefs and factors associated with TS among Indigenous adolescents(14-19years) in the CNB. We conducted a mixed-methods study in the CNB between January and November 2018, which included a qualitative study with participant observation and semi-structured interviews that focused on descriptive norms related to TS; and a cross-sectional study among public-school-going adolescents using self-administered questionnaire to report sexual behaviour and injunctive norms related to TS. Participants in the epidemiological study were also asked to submit samples for HIV, syphilis, chlamydia, and gonorrhoea testing. Qualitative thematic analysis was used to organise and analyse field notes and semi-structured interviews. Quantitative analysis included four models: TS experience and acceptance of a TS offer and the associations of these outcome variables with demographic and behavioural variables and HIV/STI infections. In the qualitative study among 20 adolescents, we found that people offering TS were reported to be from within and outside of the community, and included older men and women, and disturbingly, teachers. Participants reported feeling individual and collective agency in the decision to engage in TS and described little social sanctions for participation. In the quantitative study among 700 adolescents(309 girls[45.1%],379 boys[54.9%]), we found that girls(18.8%;58/309) and boys(15.5%;58/379) reported similar levels of having been offered TS, and of acceptance among those offered(girls 81.4% [35/43]; boys 77.8% [35/45]). TS was found to be associated with the reported forced sex and HIV/syphilis seropositivity. Due to widespread acceptance and feelings of agency, interventions would not be effective if they focused on eliminating the transactional component of sexual encounters. Instead, interventions should focus on individual and household economic stability, increasing violence reporting, bringing perpetrators to justice, and adopting condom use during all sexual encounters.

Acceptability and Usability of Self-Sampling for the Detection of Sexually Transmitted Infections Among Transgender Women: The TransOdara Multicentric Study in Brazil.

BACKGROUND: The effective testing of sexually transmitted infections (STIs) requires sampling from potential infection sites. This study aimed to assess the choice, satisfaction, and performance of self-collected samples (SCS) from potential infection sites for STI testing among transgender women in Brazil. METHODS: TransOdara was a multicentric, cross-sectional STI prevalence study conducted in 5 Brazilian cities. Using respondent-driven sampling, 1317 transgender women 18 years or older were recruited. Participants completed interviewer-led questionnaires and provided swab samples from multiple sites (anorectal, oropharyngeal, genital) for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and human papillomavirus (HPV) testing. Participants were given a choice of SCS or provider-collected samples (PCS) at each site. RESULTS: Most participants selected SCS for anorectal (74.9%; 95% confidence interval [CI], 72.4-77.3) and genital (72.7%; 95% CI, 70.2-75.1) sites, whereas fewer chose for oropharyngeal samples (49.8%; 95% CI, 47.0-52.6). For future testing, most participants expressed a preference for SCS for genital (72.2%; 95% CI, 69.5-74.7) and anorectal (70.2%; 95% CI, 67.6-72.7) sites. There was no significant difference in the positive test results for CT and NG between SCS and PCS at anorectal and oropharyngeal sites, or for HPV at anorectal and genital (penile or neovaginal) sites. CONCLUSIONS: This study demonstrated a high level of acceptability and usability of self-sampling for STI testing among transgender women. A preference for SCS was evident at the anorectal and genital sites, and the results of SCS were comparable to those of PCS. The findings suggest that multisite STI testing utilizing self-collection methods as a provided option can be effectively integrated into sexual health services for transgender women.

Ignored and undervalued in public health: a systematic review of health state utility values associated with syphilis infection.

BACKGROUND: Syphilis is a sexually transmitted infection causing significant global morbidity and mortality. To inform policymaking and economic evaluation studies for syphilis, we summarised utility and disability weights for health states associated with syphilis. METHODS: We conducted a systematic review, searching six databases for economic evaluations and primary valuation studies related to syphilis from January 2000 to February 2022. We extracted health state utility values or disability weights, including identification of how these were derived. The study was registered in the international prospective register of systematic reviews (PROSPERO, CRD42021230035). FINDINGS: Of 3401 studies screened, 22 economic evaluations, two primary studies providing condition-specific measures, and 13 burden of disease studies were included. Fifteen economic evaluations reported outcomes as disability-adjusted life years (DALYs) and seven reported quality-adjusted life years (QALYs). Fourteen of 15 economic evaluations that used DALYS based their values on the original Global Burden of Disease (GBD) study from 1990 (published in 1996). For the seven QALY-related economic evaluations, the methodology varied between studies, with some studies using assumptions and others creating utility weights or converting them from disability weights. INTERPRETATION: We found a limited evidence base for the valuation of health states for syphilis, a lack of transparency for the development of existing health state utility values, and inconsistencies in the application of these values to estimate DALYs and QALYs. Further research is required to expand the evidence base so that policymakers can access accurate and well-informed economic evaluations to allocate resources to address syphilis and implement syphilis programs that are cost-effective.

Anorectal gonorrhoea and chlamydia among transgender women in Brazil: prevalence and assessment of performance and cost of anorectal infection detection and management approaches.

OBJECTIVES: We aimed to determine the prevalence of anorectal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) among transgender women in Brazil, and to assess the performance and costs of various approaches for the diagnosis and management of anorectal NG/CT. METHODS: TransOdara was a multicentric, cross-sectional STI prevalence study among 1317 transgender women conducted in five capital cities representing all Brazilian regions. Participants aged >18 years were recruited using respondent-driven sampling (RDS), completed an interviewer-led questionnaire, offered an optional physical examination and given choice between self-collected or provider-collected samples for NG/CT testing. Performance and cost indicators of predetermined management algorithms based on the WHO recommendations for anorectal symptoms were calculated. RESULTS: Screening uptake was high (94.3%) and the estimated prevalence of anorectal NG, CT and NG and/or CT was 9.1%, 8.9% and 15.2%, respectively. Most detected anorectal NG/CT infections were asymptomatic (NG: 87.6%, CT: 88.9%), with a limited number of participants reporting any anorectal symptoms (9.1%). Of those who permitted anal examination, few had clinical signs of infection (13.6%). Sensitivity of the tested algorithms ranged from 1.4% to 5.1% (highest for treatment based on the reported anorectal discharge or ulcer and receptive anal intercourse (RAI) in the past 6 months) and specificity from 98.0% to 99.3% (highest for treatment based on the reported anorectal discharge with clinical confirmation or report of RAI). The estimated cost-per-true case of anorectal NG/CT infection treated varied from lowest providing treatment for anorectal discharge syndrome based on the reported RAI ($2.70-4.28), with algorithms including clinical examinations decreasing cost-effectiveness. CONCLUSIONS: High prevalence of mostly asymptomatic anorectal NG and CT was observed among Brazilian transgender women. Multi-site NG/CT screening should be offered to transgender women. Where diagnostic testing capacity is limited, syndromic management for those presenting with anorectal symptoms is recommended.

Sexual health challenges in migrant, immigrant, and displaced populations 2022-2023.

PURPOSE OF REVIEW: This article reviews recently published research on sexual health challenges and HIV and sexually transmitted infections (STIs) among migrant, immigrant and displaced people (MIDP) worldwide. We aimed to identify current evidence gaps regarding HIV/STI epidemiology, sexual health needs and interventions. RECENT FINDINGS: Incidence and prevalence of HIV, hepatitis B virus, hepatitis C virus and syphilis were higher among MIDP compared to host populations. However, research studies are limited in geographical distribution and few routine surveillance data are collected. Barriers to sexual health services use and participation in preventive interventions include low HIV/STI symptom knowledge and risk awareness, and intersectional experiences of stigma/discrimination. Better targeted promotion messages are needed to increase utilization of preventive sexual health interventions. SUMMARY: Access to, and use of, sexual health services and interventions are evident needs among MIDP. These needs are intertwined with social determinants of health, including cultural/language barriers and stigma. Effective interventions require involvement of multiple stakeholder groups, encouraging engagement and providing social protection. Promising directions for interventions and further research include developing sexual health supportive environments through peer-strategies and provider training in trauma-informed care.

Association of naturally acquired type-specific HPV antibodies and subsequent HPV re-detection: systematic review and meta-analysis.

BACKGROUND: Understanding the role of naturally acquired (i.e., infection-induced) human papillomavirus (HPV) antibodies against reinfection is important given the high incidence of this sexually transmitted infection. However, the protective effect of naturally acquired antibodies in terms of the level of protection, duration, and differential effect by sex remains incompletely understood. We conducted a systematic review and a meta-analysis to (1) strengthen the evidence on the association between HPV antibodies acquired through past infection and subsequent type-specific HPV detection, (2) investigate the potential influence of type-specific HPV antibody levels, and (3) assess differential effects by HIV status. METHODS: We searched Embase and Medline databases to identify studies which prospectively assessed the risk of type-specific HPV detection by baseline homologous HPV serostatus among unvaccinated individuals. Random-effect models were used to pool the measures of association of naturally acquired HPV antibodies against subsequent incident detection and persistent HPV positivity. Sources of heterogeneity for each type were assessed through subgroup analyses stratified by sex, anatomical site of infection, male sexual orientation, age group, and length of follow-up period. Evidence of a dose-response relationship of the association between levels of baseline HPV antibodies and type-specific HPV detection was assessed. Finally, we pooled estimates from publications reporting associations between HPV serostatus and type-specific HPV detection by baseline HIV status. RESULTS: We identified 26 publications (16 independent studies, with 62,363 participants) reporting associations between baseline HPV serostatus and incident HPV detection, mainly for HPV-16 and HPV-18, the most detected HPV type. We found evidence of protective effects of baseline HPV seropositivity and subsequent detection of HPV DNA (0.70, 95% CI 0.61-0.80, NE = 11) and persistent HPV positivity (0.65, 95% CI 0.42-1.01, NE = 5) mainly for HPV-16 among females, but not among males, nor for HPV-18. Estimates from 8 studies suggested a negative dose-response relationship between HPV antibody level and subsequent detection among females. Finally, we did not observe any differential effect by baseline HIV status due to the limited number of studies available. CONCLUSION: We did not find evidence that naturally acquired HPV antibodies protect against subsequent HPV positivity in males and provide only modest protection among females for HPV-16. One potential limitation to the interpretation of these findings is potential misclassification biases due to different causes.

"You are the first person to ask me how I'm doing sexually": sexual and reproductive health needs and sexual behaviours among migrant people in transit through Panama.

Background: Unprecedented numbers of migrant people transiting through the Darién Gap at the Panama-Colombia border were recorded in 2021 and 2022. Data on sexual and reproductive health (SRH) needs and service provision among migrant people in transit is generally extremely sparse. This study aimed to collect personal accounts of sexual behaviours and SRH needs and access to services among migrant people in transit through Panama. Methods: We conducted a rapid-assessment qualitative study using semi-structured interviews during June-July 2022. Participants were migrant people in transit at three locations across Panama: (i) at the Migrant Reception Station (MRS) in Darién province at the Panama-Colombia border, (ii) in the city of David near the Costa Rica-Panama border, and (iii) at the Costa Rica-Panama border. Migrant peoples (>18 years) were invited to participate using purposive sampling. Results: Overall, 26 adult migrant people (16 men, 10 women) across the three sites participated in the study. We identified three overarching themes from the interviews: (1) increased need for SRH service provision, (2) experiences of sex, relationships, and transactional sex, and (3) vulnerability to exploitation and sexual violence. All accounts reported that no formal SRH care was present during the journey through the Gap and described as inconsistent at the MRS in Darién. Provision of gynaecological or genital examinations, laboratory testing for urinary tract or STI, and prenatal care were mentioned to be the most pressing needs. Participants reported a change in their sexual behaviour while travelling, whether a decline in sexual libido or preference towards short-term partners. Most female participants recounted constantly fearing sexual violence during the journey through the Gap and several respondents reported witnessing incidents of sexual and other forms of violence. Conclusion: There are significant unmet needs regarding SRH care during the journey of migrant people transiting through the Darién Gap, at the MRS in the Darién province, and across Panama. Provision of antenatal care, rapid testing for HIV/STI, condom distribution, and care for victims of sexual violence would significantly reduce adverse SRH outcomes and improve the well-being of migrant people, even when in transit.

Effect of the "universal test and treat" policy on the characteristics of persons registering for HIV care and initiating antiretroviral therapy in Uganda.

We examined the effect of the Universal Test and Treat (UTT) policy on the characteristics of people living with HIV (PLHIV) at enrolment in HIV care and initiation of antiretroviral therapy (ART) in Uganda using data from 11 nationally representative clinics of The AIDS Support Organisation (TASO). We created two retrospective PLHIV cohorts: pre-UTT (2004-2016), where ART initiation was conditional on CD4 cell count and UTT (2017-2022), where ART was initiated regardless of World Health Organisation (WHO) clinical stage or CD4 cell count. We used a two-sample test of proportions and Wilcoxon rank-sum test to compare proportions and medians, respectively, between the cohorts. A total of 244,693 PLHIV were enrolled at the clinics [pre-UTT, 210,251 (85.9%); UTT, 34,442 (14.1%)]. Compared to the pre-UTT cohort, the UTT cohort had higher proportions of PLHIV that were male (p < 0.001), aged 18-29 years (p < 0.001), aged >69 years, never married (p < 0.001), and educated to primary (p < 0.001) and post-primary (p < 0.001) school level at enrolment in HIV care and ART initiation. Overall, 97.9% of UTT PLHIV initiated ART compared to 45.2% under pre-UTT. The median time from enrolment in HIV care to ART initiation decreased from 301 [interquartile range (IQR): 58-878] pre-UTT to 0 (IQR: 0-0) under UTT. The median CD4 count at ART initiation increased from 254 cells/µL pre-UTT to 482 cells/µL under UTT (p < 0.001). Compared to the pre-UTT cohort, the UTT cohort had higher proportions of PLHIV with a CD4 count >500 cells/µL (47.3% vs. 13.2%, p < 0.001) and WHO stage 1 (31.7% vs. 4.5%, p < 0.001) at ART initiation. Adoption of the UTT policy in Uganda was successful in enrolling previously unreached individuals, such as men and younger and older adults, as well as those with less advanced HIV disease. Future research will investigate the effect of UTT on long-term outcomes such as retention in care, HIV viral suppression, morbidity, and mortality.

The population impact of herpes simplex virus type 2 (HSV-2) vaccination on the incidence of HSV-2, HIV and genital ulcer disease in South Africa: a mathematical modelling study.

BACKGROUND: Evidence suggests HSV-2 infection increases HIV acquisition risk and HIV/HSV-2 coinfection increases transmission risk of both infections. We analysed the potential impact of HSV-2 vaccination in South Africa, a high HIV/HSV-2 prevalence setting. METHODS: We adapted a dynamic HIV transmission model for South Africa to incorporate HSV-2, including synergistic effects with HIV, to evaluate the impact of: (i) cohort vaccination of 9-year-olds with a prophylactic vaccine that reduces HSV-2 susceptibility; (ii) vaccination of symptomatically HSV-2-infected individuals with a therapeutic vaccine that reduces HSV shedding. FINDINGS: An 80% efficacious prophylactic vaccine offering lifetime protection with 80% uptake could reduce HSV-2 and HIV incidence by 84.1% (95% Credibility Interval: 81.2-86.0) and 65.4% (56.5-71.6) after 40 years, respectively. This reduces to 57.4% (53.6-60.7) and 42.1% (34.1-48.1) if efficacy is 50%, 56.1% (53.4-58.3) and 41.5% (34.2-46.9) if uptake is 40%, and 29.4% (26.0-31.9) and 24.4% (19.0-28.7) if protection lasts 10 years. An 80% efficacious therapeutic vaccine offering lifetime protection with 40% coverage among symptomatic individuals could reduce HSV-2 and HIV incidence by 29.6% (21.8-40.9) and 26.4% (18.5-23.2) after 40 years, respectively. This reduces to 18.8% (13.7-26.4) and 16.9% (11.7-25.3) if efficacy is 50%, 9.7% (7.0-14.0) and 8.6% (5.8-13.4) if coverage is 20%, and 5.4% (3.8-8.0) and 5.5% (3.7-8.6) if protection lasts 2 years. INTERPRETATION: Prophylactic and therapeutic vaccines offer promising approaches for reducing HSV-2 burden and could have important impact on HIV in South Africa and other high prevalence settings. FUNDING: WHO, NIAID.

Regional and country-level trends in cervical cancer screening coverage in sub-Saharan Africa: A systematic analysis of population-based surveys (2000-2020).

BACKGROUND: Sub-Saharan Africa (SSA) has the highest cervical cancer (CC) burden globally-worsened by its HIV epidemics. In 2020, the World Health Organization (WHO) introduced a CC elimination strategy with goals for vaccination, screening, and treatment. To benchmark progress, we examined temporal trends in screening coverage, percent screened at least twice by the age of 45, screening coverage among women living with HIV (WLHIV), and pre-cancer treatment coverage in SSA. METHODS AND FINDINGS: We conducted a systematic analysis of cross-sectional population-based surveys. It included 52 surveys from 28 countries (2000 to 2020) with information on CC screening among women aged 25 to 49 years (N = 151,338 women). We estimated lifetime and past 3-year screening coverage by age, year, country, and HIV serostatus using a Bayesian multilevel model. Post-stratification and imputations were done to obtain aggregate national, regional, and SSA-level estimates. To measure re-screening by age 45, a life table model was developed. Finally, self-reported pre-cancer treatment coverage was pooled across surveys using a Bayesian meta-analysis. Overall, an estimated 14% (95% credible intervals [95% CrI]: 11% to 21%) of women aged 30 to 49 years had ever been screened for CC in 2020, with important regional and country-level differences. In Eastern and Western/Central Africa, regional screening coverages remained constant from 2000 to 2020 and WLHIV had greater odds of being screened compared to women without HIV. In Southern Africa, however, screening coverages increased and WLHIV had equal odds of screening. Notably this region was found to have higher screening coverage in comparison to other African regions. Rescreening rates were high among women who have already been screened; however, it was estimated that only 12% (95% CrI: 10% to 18%) of women had been screened twice or more by age 45 in 2020. Finally, treatment coverage among 4 countries with data was 84% (95% CrI: 70% to 95%). Limitations of our analyses include the paucity of data on screening modality and the few countries that had multiple surveys. CONCLUSION: Overall, CC screening coverage remains sub-optimal and did not improve much over the last 2 decades, outside of Southern Africa. Action is needed to increase screening coverage if CC elimination is to be achieved.

Monitoring SARS-CoV-2 seroprevalence over time among pregnant women admitted to delivery units: Suitability for surveillance.

OBJECTIVES: To determine SARS-CoV-2 seroprevalence over time and risk factors among pregnant women at delivery in São Paulo, Brazil; and to evaluate the suitability of pregnant women as a sentinel population for SARS-CoV-2 serosurveillance. METHODS: Unselected consecutive pregnant women presenting at the labor ward of a single large hospital between July 20th 2020 to February 21st 2021 were enrolled and tested for SARS-CoV-2 serology using two assays: the rapid chromatic Wondfo One Step (for total IgA and IgG detection) and Roche Elecsys assay (detecting anti-nucleoprotein [N] IgG). SARS-CoV-2 seroprevalence was computed as smooth spline function over time with 95% confidence intervals (CI). Risk factors were evaluated for positivity by each assay. We compared timepoint seroprevalence by the two assays with four concomitant community household surveys (HHS), in which the Roche assay was used, to determine the sensitivity and relevance of the pregnant women population as sentinel population. RESULTS: Overall SARS-CoV-2 seroprevalence was 28.9% (221/763) by Roche and 17.9% (137/763) by Wondfo. Reported symptoms experienced during pregnancy were all significantly correlated with being SARS-CoV-2 seropositive at delivery with any assay (with odds-ratios ranging from 3.0 [95% CI: 2.1-4.3] for coryza to 22.8 [95% CI: 12.3-46.6] for ageusia). Seropositivity by either assay was high in women at delivery in the early period of the pandemic (June 2020), compared with seropositivity in women from the concomitant HHS: 44.1% (95% CI: 21.8-66.4) for Roche, 54.1% (30.9-78.5) for Wondfo, versus 11.4% (95% CI: 9.2-13.6) for HHS. For later periods (October 2020 and January 2021), the seropositivity in women at delivery measured by Roche corresponded well with the prevalence found among women in the HHS using the same assay, whilst prevalence measured by Wondfo dropped. CONCLUSIONS: Women at delivery represent a highly exposed and readily accessible population for sentinel surveillance of emerging infections such as SARS-CoV-2.

Post-Viral Fatigue Following SARS-CoV-2 Infection during Pregnancy: A Longitudinal Comparative Study.

Studies reported post-COVID-19 fatigue in the general population, but not among pregnant women. Our objectives were to determine prevalence, duration, and risk factors of post-viral fatigue among pregnant women with SARS-CoV-2. This study involved 588 pregnant women with SARS-CoV-2 during pregnancy or delivery in Brazil. Three groups were investigated: G1 (n = 259, symptomatic infection during pregnancy); G2 (n = 131, positive serology at delivery); G3 (n = 198, negative serology at delivery). We applied questionnaires investigating fatigue at determined timepoints after infection for G1, and after delivery for all groups; fatigue prevalence was then determined. Cox regression was used to estimate hazard ratio (HR) and 95% CI of the risk of remaining with fatigue in G1. Overall fatigue prevalence in G1 at six weeks, three months and six months were 40.6%, 33.6%, and 27.8%, respectively. Cumulative risk of remaining with fatigue increased over time, with HR of 1.69 (95% CI: 0.89-3.20) and 2.43 (95% CI: 1.49-3.95) for women with moderate and severe symptoms, respectively. Multivariate analysis showed cough and myalgia as independent risk factors in G1. Fatigue prevalence was significantly higher in G1 compared to G2 and G3. Post-viral fatigue prevalence is higher in women infected during pregnancy; fatigue's risk and duration increased with the severity of infection.

Diagnostic accuracy of cervical cancer screening strategies for high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) among women living with HIV: A systematic review and meta-analysis.

Background: We systematically reviewed the diagnostic accuracy of cervical cancer screening and triage strategies in women living with HIV (WLHIV). Methods: Cochrane Library, Embase, Global Health and Medline were searched for randomised controlled trials, prospective or cross-sectional studies published from database inception to 15 July 2022 reporting diagnostic accuracy of tests in cervical cancer screening and triage of screen-positive WLHIV. Studies were included if they reported the diagnostic accuracy of any cervical cancer screening or triage strategies for the detection of histologically-confirmed high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) among WLHIV. Summary data were extracted from published reports. Authors were contacted for missing data where applicable. Sensitivity and specificity estimates for CIN2/3+ were pooled using models for meta-analysis of diagnostic accuracy data. Study quality was assessed using the QUADAS-2 tool for the quality assessment of diagnostic accuracy studies. PROSPERO registration:CRD42020189031. Findings: In 38 studies among 18,737 WLHIV, the majority (n=19) were conducted in sub-Saharan Africa. The pooled prevalence was 12.0% (95%CI:9.8-14.1) for CIN2+ and 6.7% (95%CI:5.0-8.4) for CIN3+. The proportion of screen-positive ranged from 3-31% (visual inspection using acetic acid[VIA]); 2-46% (high-grade squamous intraepithelial lesions, and greater [HSIL+] cytology); 20-64% (high-risk[HR]-HPV DNA). In 14 studies, sensitivity and specificity of VIA were variable limiting the reliability of pooled estimates. In 5 studies where majority had histology-confirmed CIN2+, pooled sensitivity was 56.0% (95%CI:45.4-66.1; I2=65%) for CIN2+ and 65.0% (95%CI:52.9-75.4; I2 =42%) for CIN3+; specificity for

Immunogenicity and safety of one-dose human papillomavirus vaccine compared with two or three doses in Tanzanian girls (DoRIS): an open-label, randomised, non-inferiority trial.

BACKGROUND: An estimated 15% of girls aged 9-14 years worldwide have been vaccinated against human papillomavirus (HPV) with the recommended two-dose or three-dose schedules. A one-dose HPV vaccine schedule would be simpler and cheaper to deliver. We report immunogenicity and safety results of different doses of two different HPV vaccines in Tanzanian girls. METHODS: In this open-label, randomised, phase 3, non-inferiority trial, we enrolled healthy schoolgirls aged 9-14 years from Government schools in Mwanza, Tanzania. Eligible participants were randomly assigned to receive one, two, or three doses of either the 2-valent vaccine (Cervarix, GSK Biologicals, Rixensart) or the 9-valent vaccine (Gardasil-9, Sanofi Pasteur MSD, Lyon). The primary outcome was HPV 16 specific or HPV 18 specific seropositivity following one dose compared with two or three doses of the same HPV vaccine 24 months after vaccination. Safety was assessed as solicited adverse events up to 30 days after each dose and unsolicited adverse events up to 24 months after vaccination or to last study visit. The primary outcome was done in the per-protocol population, and safety was analysed in the total vaccinated population. This study was registered in ClinicalTrials.gov, NCT02834637. FINDINGS: Between Feb 23, 2017, and Jan 6, 2018, we screened 1002 girls for eligibility. 72 girls were excluded. 930 girls were enrolled and randomly assigned to receive one dose of Cervarix (155 participants), two doses of Cervarix (155 participants), three doses of Cervarix (155 participants), one dose of Gardasil-9 (155 participants), two doses of Gardasil-9 (155 participants), or three doses of Gardasil-9 (155 participants). 922 participants received all scheduled doses within the defined window (three withdrew, one was lost to follow-up, and one died before completion; two received their 6-month doses early, and one received the wrong valent vaccine in error; all 930 participants were included in the total vaccinated cohort). Retention at 24 months was 918 (99%) of 930 participants. In the according-to-protocol cohort, at 24 months, 99% of participants who received one dose of either HPV vaccine were seropositive for HPV 16 IgG antibodies, compared with 100% of participants who received two doses, and 100% of participants who received three doses. This met the prespecified non-inferiority criteria. Anti-HPV 18 seropositivity at 24 months did not meet non-inferiority criteria for one dose compared to two doses or three doses for either vaccine, although more than 98% of girls in all groups had HPV 18 antibodies. 53 serious adverse events (SAEs) were experienced by 42 (4·5%) of 930 girls, the most common of which was hospital admission for malaria. One girl died of malaria. Number of events was similar between groups and no SAEs were considered related to vaccination. INTERPRETATION: A single dose of the 2-valent or 9-valent HPV vaccine in girls aged 9-14 years induced robust immune responses up to 24 months, suggesting that this reduced dose regimen could be suitable for prevention of HPV infection among girls in the target age group for vaccination. FUNDING: UK Department for International Development/UK Medical Research Council/Wellcome Trust Joint Global Health Trials Scheme, The Bill & Melinda Gates Foundation, and the US National Cancer Institute. TRANSLATION: For the KiSwahili translation of the abstract see Supplementary Materials section.

Immunogenicity, safety, and efficacy of the HPV vaccines among people living with HIV: A systematic review and meta-analysis.

Background: Vaccines have been demonstrated to protect against high-risk human papillomavirus infection (HPV), including HPV-16/18, and cervical lesions among HIV negative women. However, their efficacy remains uncertain for people living with HIV (PLHIV).We systematically reviewed available evidence on HPV vaccine on immunological, virological, or other biological outcomes in PLHIV. Methods: We searched five electronic databases (PubMed, Medline and Embase, clinicaltrials.gov and the WHO clinical trial database) for longitudinal prospective studies reporting immunogenicity, virological, cytological, histological, clinical or safety endpoints following prophylactic HPV vaccination among PLHIV. We included studies published by February 11th, 2021. We summarized results, assessed study quality, and conducted meta-analysis and subgroup analyses, where possible. Findings: We identified 43 publications stemming from 18 independent studies (Ns =18), evaluating the quadrivalent (Ns =15), bivalent (Ns =4) and nonavalent (Ns =1) vaccines. A high proportion seroconverted for the HPV vaccine types. Pooled proportion seropositive by 28 weeks following 3 doses with the bivalent, quadrivalent, and nonavalent vaccines were 0.99 (95% confidence interval: 0.95-1.00, Ns =1), 0.99 (0.98-1.00, Ns =9), and 1.00 (0.99-1.00, Ns =1) for HPV-16 and 0.99 (0.96-1.00, Ns =1), 0.94 (0.91-0.96, Ns =9), and 1.00 (0.99-1.00, Ns =1) for HPV-18, respectively. Seropositivity remained high among people who received 3 doses despite some declines in antibody titers and lower seropositivity over time, especially for HPV-18, for the quadrivalent than the bivalent vaccine, and for HIV positive than negative individuals. Seropositivity for HPV-18 at 29-99 weeks among PLHIV was 0.72 (0.66-0.79, Ns =8) and 0.96 (0.92-0.99, Ns =2) after 3 doses of the quadrivalent and bivalent vaccine, respectively and 0.94 (0.90-0.98, Ns =3) among HIV-negative historical controls. Evidence suggests that the seropositivity after vaccination declines over time but it can lasts at least 2-4 years. The vaccines were deemed safe among PLHIV with few serious adverse events. Evidence of HPV vaccine efficacy against acquisition of HPV infection and/or associated disease from the eight trials available was inconclusive due to the low quality. Interpretation: PLHIV have a robust and safe immune response to HPV vaccination. Antibody titers and seropositivity rates decline over time but remain high. The lack of a formal correlate of protection and efficacy results preclude definitive conclusions on the clinical benefits. Nevertheless, given the burden of HPV disease in PLHIV, although the protection may be shorter or less robust against HPV-18, the robust immune response suggests that PLHIV may benefit from receiving HPV vaccination after acquiring HIV. Better quality studies are needed to demonstrate the clinical efficacy among PLHIV. Funding: World Health Organization. MRC Centre for Global Infectious Disease Analysis, Canadian Institutes of Health Research, UK Medical Research Council (MRC).

Impact of SARS-CoV-2 on pregnancy and neonatal outcomes: An open prospective study of pregnant women in Brazil.

OBJECTIVES: To determine the incidence and risk of adverse obstetric and neonatal outcomes according to SARS-CoV-2 infection severity in pregnant women. METHOD: Open prospective study of pregnant women tested for SARS-CoV-2 by serological and molecular assays during pregnancy or delivery in two hospitals in Sao Paulo, Brazil from April 12, 2020, to February 28, 2021. Five groups were considered for analysis: C0, negative COVID-19 results and no COVID-19 symptoms; C1, positive COVID-19 results, and no symptoms; C2, positive COVID-19 results with mild symptoms; C3, positive COVID-19 results with moderate symptoms; and C4, positive COVID-19 results with severe symptoms. The association between obstetric and neonatal outcomes and COVID-19 severity was determined using multivariate analysis. RESULTS: 734 eligible pregnant women were enrolled as follows: C0 (n = 357), C1 (n = 127), C2 (n = 174), C3 (n = 37), and C4 (n = 39). The following pregnancy and neonatal outcomes were associated with severe COVID-19: oligohydramnios (adjusted Odds Ratio [aOR] = 6.18; 95% CI 1.87‒20.39), fetal distress (aOR = 4.01; 95% Confidence Interval [CI] 1.84‒8.75), preterm birth (aOR = 5.51; 95% CI 1.47‒20.61), longer hospital stay (aOR = 1.66; 95% CI 1.36‒2.02), and admission to the neonatal intensive care unit (aOR = 19.36; 95% CI, 5.86‒63.99). All maternal (n = 6, 15.4%, p < 0.001) and neonatal (n = 5, 12.5%, p < 0.001) deaths and most fetal deaths (n = 4, 9.8%, p < 0.001) occurred in C4 group. Moderate COVID-19 was associated with oligohydramnios (aOR = 6.23; 95% CI 1.93‒20.13) and preterm birth (aOR = 3.60; 95% CI 1.45‒9.27). Mild COVID-19 was associated with oligohydramnios (aOR = 3.77; 95% CI 1.56‒9.07). CONCLUSION: Adverse pregnancy and neonatal outcomes were associated with maternal symptomatic COVID-19 status, and risk increased with disease severity.

Barriers and facilitators to antiretroviral adherence and retention in HIV care among people living with HIV in the Comarca Ngäbe-Buglé, Panama.

INTRODUCTION: Panama's HIV epidemic is far from under control. One of the populations with the fastest-growing epidemic among the Indigenous peoples of the Comarca Ngäbe-Buglé (CNB). The CNB is an administratively autonomous Indigenous region in Western Panama that is home to over 200,000 individuals of Ngäbe and Buglé ethnicities. This population is unique and, in several ways, represents the early stages of the AIDS epidemics in high-income countries. The CNB is the most impoverished region in Panama and is relatively isolated from outside influences, with limited roads, electricity, and an internet connection, including medical assistance. Around 1.5% of all rapid HIV tests are positive, compared to a national prevalence of 0.9%; in CNB, diagnosis tends to be late. In CNB, 56.3% of individuals had an initial CD4 count of <350 cells/mm3. Antiretroviral treatment (ART) dropout in this region is five times higher than the national average; there is high early mortality due to opportunistic infections. Using the Social-Ecological Theory for Health as a framework, this study aims to describe the facilitators and barriers associated with ART adherence and retention in HIV care among people living with HIV (PLHIV) in the CNB. A better understanding of factors that obstruct adherence could lead to more effective HIV care and prevention in CNB. METHODS: We conducted 21 semi-structured interviews with PLHIV who reside across all three regions of the CNB and have attended an antiretroviral (ART) clinic at least once. Deductive thematic analysis was used to uncover themes related ART adherence and retention in HIV care at the individual, social and structural levels. DISCUSSION: This unique, isolated population of rural Indigenous peoples has high infection rates, late diagnosis, poor ART adherence, and high AIDS-related death rates. The CNB is an important region to examen ART adherence and retention in care. We determined that psychological health, social support, and discrimination acted as individual-level facilitators and barriers to adherence and retention. Notably, structural barriers included difficult access to ART care due to travel costs, ART shortages, and uncooperative Western/Traditional medical systems. Recommended interventions used in other Low- and Middle-Income settings include increasing peer and family-level support and community knowledge and understanding of HIV infection. Additionally, our study suggests structural interventions, including decreasing the cost and distance of traveling to the ART clinic, by decentralizing services, decreasing food scarcity, and increasing collaboration between Western and Traditional providers.

Determinants of human papillomavirus (HPV) vaccine uptake among girls in France: A population-based telephone survey.

INTRODUCTION: The uptake of human papillomavirus (HPV) vaccination in France remains low. The aim of this study was to identify factors associated with the uptake of the HPV vaccine in girls aged 11-14 years in France. METHODS: We conducted a telephone survey among a quota sample of 1102 mothers of 11-14-year-old daughters residing in mainland France, using the French Survey Questionnaire for the Determinants of HPV Vaccine Hesitancy (FSQD-HPVH). The dependent variable was the uptake of at least one dose of the HPV vaccine in the daughter. The independent variables included the FSQD-HPVH item variables, the Global Vaccine Confidence Index item variables, the daughter's age, and the mother's socioeconomic status. RESULTS: Overall, 38.6% of the mothers indicated that their daughter received at least one dose of the HPV vaccine. The multivariate analysis revealed that agreeing with the statement that doctors/health care providers believe vaccinating girls against HPV was a good idea, and having asked questions to the attending doctor about HPV vaccines were associated with a higher HPV vaccine uptake (OR = 4.99 , 95% CI [2.09-11.89]; and OR = 3.44, 95% CI [2.40-4.92]). Mother's belief that her daughter was too young to be vaccinated against HPV (OR = 0.16 , 95% CI [0. 09-0.29]) and lower daughter's age (OR = 0.17 , 95% CI [0.10-0.28] for girls aged 11 compared to those aged 14) were found strongly inversely associated with HPV vaccination, followed by agreeing with the statement that the HPV vaccine was unsafe (OR = 0.42 , 95% CI [0.26-0.67]), identifying as true the statement that HPV was very rare (OR = 0.49 , 95% CI [0.31-0.77]), and the mother's refusal of own vaccination (OR = 0.57 , 95% CI [0.40-0.80]). CONCLUSION: We have identified important determinants associated with HPV vaccine uptake in France. Interventions designed to improve HPV vaccine uptake should be tailored to address these determinants.

Acceptability of self-sampling for etiological diagnosis of mucosal sexually transmitted infections (STIs) among transgender women in a longitudinal cohort study in São Paulo, Brazil.

This study conducted among transgender women in São Paulo, Brazil assessed the acceptability and suitability of screening sexually transmitted infections (STIs), such as Chlamydia trachomatis and Neisseria gonorrhoeae, by sampling multiple anatomical sites (i.e. urethral, anorectal, oropharyngeal, and neovaginal), and utilizing self- or provider-collection methods. First, a convenience sample of 23 cohort participants were recruited during a scheduled study visit between October and November 2018. Data collection was through a short investigator-led quantitative survey in Portuguese, and included presentation of investigator-designed, gender-neutral instructional diagrams to guide self-sampling. Three supplemental focus group discussions (FGDs) with a total of 30 participants guided by semi-structured script were conducted in Portuguese between September and October 2019. All participants reported being assigned male sex at birth and self-identified with a feminine gender identity at time of study. All survey respondents (100%; n = 23) indicated willingness to provide samples for STI screening during a future study visit. Preference was for self-collection of urine samples (83%; n = 19), urethral swabs (82%; n = 18), and anorectal swabs (77%; n = 17). A lower preference for self-collection of oropharyngeal swabs (48%; n = 11) was observed. Most respondents (78%; n = 18) indicated that they would not prefer specimens to be collected by a health professional, mainly due to 'more privacy' (72%; n = 13). All respondents indicated that they would feel comfortable to provide a self-collected sample based on instructional diagrams shown. In FGDs, although the collection by a health professional was described as a technically safer option for some participants, there was a preference for self-collection to avoid discomfort and embarrassment in exposing the body. Overall, this sub-study suggested acceptability among transgender women of introducing self-sampling for etiological diagnosis of STIs from potential infection sites. Uptake and usability will be explored further in a cross-sectional STI prevalence study of transgender women in Brazil.