A High Burden of Asymptomatic Genital Tract Infections Undermines the Syndromic Management Approach Among Adolescents and Young Adults in South Africa: Implications for HIV Prevention Efforts

Background  Youth in southern Africa, particularly adolescent girls and young women, are a key population for HIV prevention interventions. Untreated genital tract infections (GTIs) increase both HIV transmission and acquisition risks. South African GTI treatment guidelines employ syndromic management, which relies on individuals to report GTI signs and symptoms. Syndromic management may, however, underestimate cases, particularly among youth. We compared genital tract infection (GTI) prevalence by symptom-based and laboratory assessment among sexually-experienced youth in South Africa, overall and stratified by sex. Methods  Interviewer-administered surveys assessed socio-demographics, behaviors, and GTI symptoms among 352 youth (16-24 yrs., HIV-negative or unknown HIV status at enrollment) enrolled in community-based cohorts in Durban and Soweto (2014–2016). Laboratory tests assessed HIV, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), Trichomonas vaginalis (TV) infections and, among females, bacterial vaginosis (BV) and Candida species. Youth with genital ulcers were tested for HSV-2 and syphilis. We assessed sensitivity (and specificity) of symptom-based reporting in identifying laboratory-confirmed GTIs. Results  At baseline, 16.2% of females (32/198) and < 1% (1/154) of males reported ≥1 GTI symptom. However, laboratory tests identified ≥1 GTI in 70.2% and 10.4%, respectively. Female CT prevalence was 18.2%, NG 7.1%, MG 9.6%, TV 8.1%, and 5.1% were newly diagnosed with HIV. BV prevalence was 53.0% and candidiasis 9.6%. One female case of herpes was identified (0 syphilis). Male CT prevalence was 7.8%, NG 1.3%, MG 3.3%, TV < 1%, and 2.0% were newly diagnosed with HIV. Overall, 77.8% of females and 100% of males with laboratory-diagnosed GTIs reported no symptoms or were asymptomatic. Sensitivity (and specificity) of symptom-based reporting was 14% (97%) among females and 0% (99%) among males. Conclusion  A high prevalence of asymptomatic GTIs and very poor sensitivity of symptom-based reporting undermines the applicability of syndromic GTI management, thus compromising GTI control and HIV prevention efforts among youth. Syndromic GTI management does not meet the sexual health needs of young people. Policy changes incorporating innovations in GTI diagnostic testing are needed to reduce GTIs and HIV-associated risks among youth

Effect of Patient Education and Non-medication Based Referrals to Reduce the use of Opioids and Benzodiazepines an Outpatient Clinic Setting

Researc

A Qualitative Exploration to Understand Barriers and Facilitators to Daily Oral PrEP uptake and sustained adherence among HIV-negative women planning for or with pregnancy in rural Southwestern Uganda

Introduction: Antiretroviral pre-exposure prophylaxis (PrEP) may reduce periconception and pregnancy HIV incidence among women in settings, where gender power imbalances limit HIV testing, engagement in care and HIV viral suppression. We conducted qualitative interviews to understand factors influencing periconception and pregnancy PrEP uptake and use in a cohort of women (Trial registration: NCT03832530) offered safer conception counselling in rural Southwestern Uganda, where PrEP uptake was high. Methods: Between March 2018 and January 2019, in-depth interviews informed by conceptual frameworks for periconception risk reduction and PrEP adherence were conducted with 37 women including those with ≥80% an

Sexually transmitted infection (STI) knowledge and perceptions among people in HIV-sero-different partnerships in rural southwestern Uganda.

Globally, over one million people acquire curable sexually transmitted infections (STI) each day. Understanding how people think about STIs is key to building culturally appropriate STI prevention and treatment programs. We explored STI knowledge and perceptions in rural, southwestern Uganda to inform future interventions. From August 2020 to December 2020, we conducted individual in-depth interviews among adult men and women (≥18 years) with recent or current personal or partner pregnancy, a history of an STI diagnosis and treatment, and membership in an HIV-sero-different relationship. Interviews explored STI knowledge, perceptions, and barriers and facilitators to engaging in STI care. We used inductive and deductive approaches to generate a codebook guided by the healthcare literacy skills framework in a thematic analysis. Ten men with STI, five of their female partners, eighteen women with STI, and four of their male partners participated in individual in-depth interviews. The median age was 41 (range 27-50) for men and 29 (range 22-40) for women. Sixteen (43%) participants were with HIV. Significant themes include: 1) Participants obtained STI knowledge and information from the community (friends, family members, acquaintances) and medical professionals; 2) While participants knew STIs were transmitted sexually, they also believed transmission occurred via non-sexual mechanisms. 3) Participants associated different connotations and amounts of stigma with each STI, for example, participants reported that syphilis was passed down "genetically" from parent to child. 4) Participants reported uncertainty about whether STIs affected pregnancy outcomes and whether antenatal STI treatment was safe. The complicated nature of STIs has led to understandable confusion in settings without formal sexual healthcare education. Robust counseling and education prior to sexual debut will help allow men and women to understand the signs, symptoms, and treatments necessary for STI cure and to navigate often complicated and overburdened healthcare systems

Overcoming Ethical Challenges to Engaging Men Who Have Sex with Women in HIV Research

Men who have sex with women are understudied in HIV research despite the extent to which they experience HIV-related mortality and contribute to the epidemic among women. During our experience of developing and piloting an HIV prevention intervention for men living with HIV in South Africa, and planning to have a child with an HIV-negative woman, ethical questions were posed regarding implementation of a male-centered intervention that did not require female partner participation. Two overarching ethical issues were the potential for (1) compromising women's reproductive and sexual autonomy and (2) increasing HIV-acquisition risks for the woman because the intervention efficacy was unknown. We describe here how these concerns were addressed to facilitate development of a male-centered HIV-prevention intervention. We hope this process manuscript will support researchers, clinicians, and reviewers to engage men who have sex with women in HIV prevention and care

STI prevalence among men living with HIV engaged in safer conception care in rural, southwestern Uganda.

HIV care provides an opportunity to integrate comprehensive sexual and reproductive healthcare, including sexually transmitted infection (STI) management. We describe STI prevalence and correlates among men living with HIV (MLWH) accessing safer conception care to conceive a child with an HIV-uninfected partner while minimizing HIV transmission risks. This study reflects an ongoing safer conception program embedded within a regional referral hospital HIV clinic in southwestern Uganda. We enrolled MLWH, planning for pregnancy with an HIV-uninfected partner and accessing safer conception care. Participants completed interviewer-administered questionnaires detailing socio-demographics, gender dynamics, and sexual history. Participants also completed STI laboratory screening for syphilis (immunochromatographic testing confirmed by rapid plasma reagin), and chlamydia, gonorrhea, trichomoniasis, and HIV-RNA via GeneXpert nucleic acid amplification testing. Bivariable associations of STI covariates were assessed using Fisher's exact test. Among the 50 men who completed STI screening, median age was 33 (IQR 31-37) years, 13/50 (26%) had ≥2 sexual partners in the prior three months, and 46/50 (92%) had HIV-RNA <400 copies/mL. Overall, 11/50 (22%) had STIs: 16% active syphilis, 6% chlamydia. All participants initiated STI treatment. STI prevalence was associated with the use of threats/intimidation to coerce partners into sex (27% vs 3%; p = 0.03), although absolute numbers were small. We describe a 22% curable STI prevalence among a priority population at higher risk for transmission to partners and neonates. STI screening and treatment as a part of comprehensive sexual and reproductive healthcare should be integrated into HIV care to maximize the health of men, women, and children

Sexually Transmitted Infection Prevalence Among Women at Risk for HIV Exposure Initiating Safer Conception Care in Rural, Southwestern Uganda

BACKGROUND: Knowledge of STI prevalence and risk factors is important to the development of tenofovir-based pre-exposure prophylaxis (PrEP) and safer conception programming. We introduced STI screening among women at risk for HIV exposure, participating in a safer conception study in southwestern Uganda. METHODS: We enrolled 131 HIV-uninfected women, planning for pregnancy with a partner living with HIV or of unknown HIV-serostatus (2018–2019). Women were offered comprehensive safer conception counseling, including PrEP. Participants completed interviewer-administered questionnaires detailing socio-demographics and sexual history. We integrated laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis as a substudy to assess STI prevalence. Multivariable logistic regression was used to determine correlates. RESULTS: Ninety-four women completed STI screening (72% of enrolled). Median age was 30 (IQR 26–34) years, and 94% chose PrEP as part of safer conception care. Overall, 24% had STIs: 13% chlamydia, 2% gonorrhea, 6% trichomoniasis, 6% syphilis, and 3% ≥2 STI. STI prevalence was associated with younger age (adjusted odds ratio [AOR] 0.87, 95% confidence interval [CI] 0.77–0.99), prior stillbirth (AOR 5.04, 95% CI 1.12–22.54), and not feeling vulnerable to HIV (AOR 16.33, 95% CI 1.12–237.94). CONCLUSION: We describe a 24% curable STI prevalence among women at risk for HIV exposure, planning for pregnancy. These data highlight the importance of integrating laboratory-based STI screening into safer conception programs to maximize the health of HIV-affected women, children, and families

Sexually Transmitted Infection Prevalence among Women at Risk for HIV Exposure Initiating Safer Conception Care in Rural, Southwestern Uganda

Background Knowledge of sexually transmitted infection (STI) prevalence and risk factors is important to the development of tenofovir-based preexposure prophylaxis (PrEP) and safer conception programming. We introduced STI screening among women at risk for HIV exposure who were participating in a safer conception study in southwestern Uganda. Methods We enrolled 131 HIV-uninfected women, planning for pregnancy with a partner living with HIV or of unknown HIV serostatus (2018-2019). Women were offered comprehensive safer conception counseling, including PrEP. Participants completed interviewer-administered questionnaires detailing sociodemographics and sexual history. We integrated laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis as a substudy to assess STI prevalence. Multivariable logistic regression was used to determine correlates. Results Ninety-four women completed STI screening (72% of enrolled). Median age was 30 (interquartile range, 26-34) years, and 94% chose PrEP as part of safer conception care. Overall, 24% had STIs: 13% chlamydia, 2% gonorrhea, 6% trichomoniasis, 6% syphilis, and 3% ≥2 STI. Sexually transmitted infection prevalence was associated with younger age (adjusted odds ratio [AOR], 0.87; 95% confidence interval [CI], 0.77-0.99), prior stillbirth (AOR, 5.04; 95% CI, 1.12-22.54), and not feeling vulnerable to HIV (AOR, 16.33; 95% CI, 1.12-237.94). Conclusions We describe a 24% curable STI prevalence among women at risk for HIV exposure who were planning for pregnancy. These data highlight the importance of integrating laboratory-based STI screening into safer conception programs to maximize the health of HIV-affected women, children, and families

High PrEP uptake and objective longitudinal adherence among HIV-exposed women with personal or partner plans for pregnancy in rural Uganda: A cohort study.

BackgroundIn Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention.Methods and findingsWe enrolled HIV-negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided in electronic pillboxes, providing the primary adherence measure ("high" adherence when pillbox was opened ≥80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined quarterly for women who acquired HIV and a randomly selected subset of those who did not; concentrations TFV ≥40 ng/mL and TFV-DP ≥600 fmol/punch were categorized as "high." Women who became pregnant were initially exited from the cohort by design; from March 2019, women with incident pregnancy remained in the study with quarterly follow-up until pregnancy outcome. Primary outcomes included (1) PrEP uptake (proportion who initiated PrEP); and (2) PrEP adherence (proportion of days with pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors selected based on our conceptual framework of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. We enrolled 131 women with mean age 28.7 years (95% CI: 27.8 to 29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex. Most women (N = 118; 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI: 83%, 90%). No covariates were associated with 3-month pill-taking behavior. Concentrations of plasma TFV and TFV-DP were high among 66% and 47%, 56% and 41%, and 45% and 45% at months 3, 6, and 9, respectively. We observed 53 pregnancies among 131 women (1-year cumulative incidence 53% [95% CI: 43%, 62%]) and 1 HIV-seroconversion in a non-pregnant woman. Mean pillcap adherence for PrEP users with pregnancy follow-up (N = 17) was 98% (95% CI: 97%, 99%). Study design limitations include lack of a control group.ConclusionsWomen in Uganda with PrEP indications and planning for pregnancy chose to use PrEP. By electronic pillcap, most were able to sustain high adherence to daily oral PrEP prior to and during pregnancy. Differences in adherence measures highlight challenges with adherence assessment; serial measures of TFV-DP in whole blood suggest 41% to 47% of women took sufficient periconception PrEP to prevent HIV. These data suggest that women planning for and with pregnancy should be prioritized for PrEP implementation, particularly in settings with high fertility rates and generalized HIV epidemics. Future iterations of this work should compare the outcomes to current standard of care.Trial registrationClinicalTrials.gov Identifier: NCT03832530 https://clinicaltrials.gov/ct2/show/NCT03832530?term=lynn+matthews&cond=hiv&cntry=UG&draw=2&rank=1

Prevalence and Causes of Diagnostic Errors in Hospitalized Patients Under Investigation for COVID-19

BackgroundThe COVID-19 pandemic required clinicians to care for a disease with evolving characteristics while also adhering to care changes (e.g., physical distancing practices) that might lead to diagnostic errors (DEs).ObjectiveTo determine the frequency of DEs and their causes among patients hospitalized under investigation (PUI) for COVID-19.DesignRetrospective cohort.SettingEight medical centers affiliated with the Hospital Medicine ReEngineering Network (HOMERuN).Target populationAdults hospitalized under investigation (PUI) for COVID-19 infection between February and July 2020.MeasurementsWe randomly selected up to 8 cases per site per month for review, with each case reviewed by two clinicians to determine whether a DE (defined as a missed or delayed diagnosis) occurred, and whether any diagnostic process faults took place. We used bivariable statistics to compare patients with and without DE and multivariable models to determine which process faults or patient factors were associated with DEs.ResultsTwo hundred and fifty-seven patient charts underwent review, of which 36 (14%) had a diagnostic error. Patients with and without DE were statistically similar in terms of socioeconomic factors, comorbidities, risk factors for COVID-19, and COVID-19 test turnaround time and eventual positivity. Most common diagnostic process faults contributing to DE were problems with clinical assessment, testing choices, history taking, and physical examination (all p &lt; 0.01). Diagnostic process faults associated with policies and procedures related to COVID-19 were not associated with DE risk. Fourteen patients (35.9% of patients with errors and 5.4% overall) suffered harm or death due to diagnostic error.LimitationsResults are limited by available documentation and do not capture communication between providers and patients.ConclusionAmong PUI patients, DEs were common and not associated with pandemic-related care changes, suggesting the importance of more general diagnostic process gaps in error propagation