for the National COVID Cohort Collaborative (N3C) Consortium IMPORTANCE Persons with immune dysfunction have a higher risk for severe COVID-19 outcomes. However, these patients were largely excluded from SARS-CoV-2 vaccine clinical trials, creating a large evidence gap.OBJECTIVE To identify the incidence rate and incidence rate ratio (IRR) for COVID-19 breakthrough infection after SARS-CoV-2 vaccination among persons with or without immune dysfunction. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study analyzed data from the National COVID Cohort Collaborative (N3C), a partnership that developed a secure, centralized electronic medical record-based repository of COVID-19 clinical data from academic medical centers across the US. Persons who received at least 1 dose of a SARS-CoV-2 vaccine between December 10, 2020, and September 16, 2021, were included in the sample.MAIN OUTCOMES AND MEASURES Vaccination, COVID-19 diagnosis, immune dysfunction diagnoses (ie, HIV infection, multiple sclerosis, rheumatoid arthritis, solid organ transplant, and bone marrow transplantation), other comorbid conditions, and demographic data were accessed through the N3C Data Enclave. Breakthrough infection was defined as a COVID-19 infection that was contracted on or after the 14th day of vaccination, and the risk after full or partial vaccination was assessed for patients with or without immune dysfunction using Poisson regression with robust SEs. Poisson regression models were controlled for a study period (before or after [pre-or post-Delta variant] June 20, 2021), full vaccination status, COVID-19 infection before vaccination, demographic characteristics, geographic location, and comorbidity burden.RESULTS A total of 664 722 patients in the N3C sample were included. These patients had a median (IQR) age of 51 (34-66) years and were predominantly women (n = 378 307 [56.9%]). Overall, the incidence rate for COVID-19 breakthrough infection was 5.0 per 1000 person-months among fully vaccinated persons but was higher after the Delta variant became the dominant SARS-CoV-2 strain (incidence rate before vs after June 20, 2021, 2.2 [95% CI, 2.2-2.2] vs 7.3 [95% CI,] per 1000 person-months). Compared with partial vaccination, full vaccination was associated with a 28% reduced risk for breakthrough infection (adjusted IRR [AIRR], 0.72; 95% CI, 0.68-0.76). People with a breakthrough infection after full vaccination were more likely to be older and women. People with HIV infection (AIRR, 1.33; 95% CI, 1.18-1.49), rheumatoid arthritis (AIRR, 1.20; 95% CI, 1.09-1.32), and solid organ transplant (AIRR, 2.16; 95% CI, 1.96-2.38) had a higher rate of breakthrough infection.CONCLUSIONS AND RELEVANCE This cohort study found that full vaccination was associated with reduced risk of COVID-19 breakthrough infection, regardless of the immune status of patients. Despite full vaccination, persons with immune dysfunction had substantially higher risk for COVID-19 breakthrough infection than those without such a condition. For persons with immune...

IMPORTANCEThe National COVID Cohort Collaborative (N3C) is a centralized, harmonized, highgranularity electronic health record repository that is the largest, most representative COVID-19 cohort to date. This multicenter data set can support robust evidence-based development of predictive and diagnostic tools and inform clinical care and policy.OBJECTIVES To evaluate COVID-19 severity and risk factors over time and assess the use of machine learning to predict clinical severity. DESIGN, SETTING, AND PARTICIPANTSIn a retrospective cohort study of 1 926 526 US adults with SARS-CoV-2 infection (polymerase chain reaction >99% or antigen <1%) and adult patients without SARS-CoV-2 infection who served as controls from 34 medical centers nationwide between January 1, 2020, and December 7, 2020, patients were stratified using a World Health Organization COVID-19 severity scale and demographic characteristics. Differences between groups over time were evaluated using multivariable logistic regression. Random forest and XGBoost models were used to predict severe clinical course (death, discharge to hospice, invasive ventilatory support, or extracorporeal membrane oxygenation). MAIN OUTCOMES AND MEASURESPatient demographic characteristics and COVID-19 severity using the World Health Organization COVID-19 severity scale and differences between groups over time using multivariable logistic regression. RESULTSThe cohort included 174 568 adults who tested positive for SARS-CoV-2 (mean [SD] age, 44.4 [18.6] years; 53.2% female) and 1 133 848 adult controls who tested negative for SARS-CoV-2 (mean [SD] age, 49.5 [19.2] years; 57.1% female). Of the 174 568 adults with SARS-CoV-2, 32 472(18.6%) were hospitalized, and 6565 (20.2%) of those had a severe clinical course (invasive ventilatory support, extracorporeal membrane oxygenation, death, or discharge to hospice). Of the hospitalized patients, mortality was 11.6% overall and decreased from 16.4% in March to April 2020 to 8.6% in September to October 2020 (P = .002 for monthly trend). Using 64 inputs available on the first hospital day, this study predicted a severe clinical course using random forest and XGBoost models (area under the receiver operating curve = 0.87 for both) that were stable over time. The factor most strongly associated with clinical severity was pH; this result was consistent across machine learning methods. In a separate multivariable logistic regression model built for inference, (continued) Key Points Question In a US data resource large enough to adjust for multiple confounders, what risk factors are associated with COVID-19 severity and severity trajectory over time, and can machine learning models predict clinical severity? Findings In this cohort study of 174 568 adults with SARS-CoV-2, 32 472 (18.6%) were hospitalized and 6565 (20.2%) were severely ill, and first-day machine learning models accurately predicted clinical severity. Mortality was 11.6%

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SUMMARYBackgroundGiven recent concerns of efavirenz reducing the efficacy of contraceptive implants, we sought to determine if pregnancy rates differ among HIV-positive women using various contraceptive methods and efavirenz- or nevirapine-based antiretroviral therapy (ART) regimens.MethodsWe conducted a retrospective cohort analysis of HIV-positive women aged 15–45 years enrolled in HIV care facilities in western Kenya from January 2011 to December 2013. Pregnancy was diagnosed clinically and the primary exposure was a combination of contraceptive method and ART regimen. We used Poisson models, adjusting for repeated measures, as well as demographic, behavioral and clinical factors, to compare pregnancy rates among women on different contraceptive/ART combinations.Findings24,560 women contributed 37,635 years of follow-up with 3,337 incident pregnancies. Among women using implants, adjusted pregnancy incidence for nevirapine- and efavirenz-based ART users were 1·1 (95% CI 0·72–1·5) and 3·3 (95% CI 1·8–4·8) per 100 women-years (w-y), respectively (adjusted incidence rate ratio (aIRR) 3·0, 95% CI 1·3–4·6). Among women using depomedroxyprogesterone acetate (DMPA), adjusted pregnancy incidence for nevirapine- and efavirenz-based ART users were 4·5 (95% CI 3·7–5·2) and 5·4 (95% CI 4·0–6·8) per 100 w-y, respectively (aIRR 1·2, 95% CI 0·91–1·5). Women using other contraceptive methods, except for intrauterine devices and permanent methods, experienced 3·1–4·1 higher rates of pregnancy than women using implants, with 1·6–2·8 higher rates specifically among women using efavirenz-based ART.InterpretationWhile HIV-positive women using implants on efavirenz-based ART faced three times higher risk of contraceptive failure than those on nevirapine-based ART, these women still experienced lower contraceptive failure rates than women on all other contraceptive methods, except for intrauterine devices and permanent methods. Guidelines for contraceptive and ART combinations should balance the failure rates for each contraceptive method and ART regimen combination against the high effectiveness of implants.FundingSupported by the President’s Emergency Plan for AIDS Relief and the Centers for Disease Control and Prevention.

IntroductionSince 2015, the World Health Organization recommends pre-exposure prophylaxis (PrEP) for all persons at substantial risk for HIV, including HIV-uninfected partners in serodiscordant relationships in resource-limited settings. As PrEP moves from clinical trials to real-world use, understanding facilitators of and barriers to PrEP initiation and adherence is critical to successful PrEP implementation and rollout.MethodsWe conducted 44 in-depth individual or couple interviews with 63 participants (30 without HIV and 33 with HIV) enrolled in the Partners Demonstration Project in Kisumu, Kenya, between August and September 2014. The semi-structured interviews discussed the following: 1) perceived advantages and disadvantages of antiretroviral therapy (ART)/PrEP; 2) reasons for accepting or declining ART/PrEP and 3) influence of prevention of transmission to partner or infant on ART/PrEP use. Transcripts from the interviews were iteratively analyzed using inductive content analysis.ResultsOur study identified three key factors that may facilitate initiation of PrEP in this population. First, participants using PrEP felt reduced stress and increased trust in their HIV serodiscordant relationships. Second, greater community-wide knowledge of PrEP was thought to likely increase PrEP acceptance. Third, greater education and counselling by providers on PrEP use was also considered to likely increase the adoption of PrEP. We also identified three key barriers to initiation of and adherence to PrEP. First, most participants who declined PrEP expressed doubts about the relative additional effectiveness of PrEP in combination with other prevention tools. Second, perceived stigma related to PrEP use was an important barrier to PrEP initiation. Third, many struggled with overcoming perceived side effects or logistical challenges of taking daily PrEP, particularly when they themselves were not ill.ConclusionsLeveraging the facilitators and overcoming barriers to PrEP uptake may enhance the successful rollout of PrEP among HIV serodiscordant couples in Kenya and other areas in sub-Saharan Africa, thereby reducing sexual transmission of HIV. Further research focused on how best to provide counselling on combination HIV prevention tools in the context of PrEP use is a crucial next step to delivering PrEP.

Disclosure of positive HIV status in Sub-Saharan Africa has been associated with safer sexual practices and better antiretroviral therapy (ART) adherence, but associations with psychosocial function are unclear. We examined patterns and psychosocial correlates of disclosure in a Zimbabwean community. Two hundred HIV positive women at different stages of initiating ART participated in a cross-sectional study examining actual disclosures, disclosure beliefs, perceived stigma, self-esteem, depression, and quality of life. Ninety-seven percent of the women disclosed to at least one person, 78% disclosed to their current husband/partner, with an average disclosure of 4.0 persons per woman. The majority (85–98%) of disclosures occurred in a positive manner and 72–95% of the individuals reacted positively. Factors significantly correlated with HIV disclosure to partners included being married, later age at menses, longer duration of HIV since diagnosis, being on ART, being more symptomatic at baseline, ever having used condoms, and greater number of partners in the last year. In multivariate analysis, being married and age at menses predicted disclosure to partners. Positive disclosure beliefs, but not the total number of disclosures, significantly correlated with lower perceived stigma (rho=0.44 for personalized subscale and rho=0.51 for public subscale, both p<0.0001), higher self-esteem (rho=0.15, p=0.04), and fewer depressive symptoms (rho=−0.14, p=0.05). In conclusion, disclosure of positive HIV status among Zimbabwean women is common and is frequently met with positive reactions. Moreover, positive disclosure beliefs correlate significantly with psychosocial measures, including lower perceived stigma, higher self-esteem, and lower depression.

IntroductionAvoiding unintended pregnancies is important for the health of adolescents living with HIV and has the additional benefit of preventing potential vertical HIV transmission. Health facility providers represent an untapped resource in understanding the barriers and facilitators adolescents living with HIV face when accessing contraception. By understanding these barriers and facilitators to contraceptive use among adolescent females living with HIV, this study aimed to understand how best to promote contraception within this marginalized population.MethodsWe conducted structured in-depth interviews with 40 providers at 21 Family AIDS Care & Education Services - supported clinics in Homabay, Kisumu and Migori counties in western Kenya from July to August 2014. Our interview guide explored the providers’ perspectives on contraceptive service provision to adolescent females living with HIV with the following specific domains: contraception screening and counselling, service provision, commodity security and clinic structure. Transcripts from the interviews were analyzed using inductive content analysis.ResultsAccording to providers, interpersonal factors dominated the barriers adolescent females living with HIV face in accessing contraception. Providers felt that adolescent females fear disclosing their sexual activity to parents, peers and providers, because of repercussions of perceived promiscuity. Furthermore, providers mentioned that adolescents find seeking contraceptive services without a male partner challenging, because some providers and community members view adolescents unaccompanied by their partners as not being serious about their relationships or having multiple concurrent relationships. On the other hand, providers noted that institutional factors best facilitated contraception for these adolescents. Integration of contraception and HIV care allows easier access to contraceptives by removing the stigma of coming to a clinic solely for contraceptive services. Youth-friendly services, including serving youth on days separate from adults, also create a more comfortable setting for adolescents seeking contraceptive services.ConclusionsProviders at these facilities identified attitudes of equating seeking contraceptive services with promiscuity by parents, peers and providers as barriers preventing adolescent females living with HIV from accessing contraceptive services. Health facilities should provide services for adolescent females in a youth-friendly manner and integrate HIV and contraceptive services.