High Prevalence of Unconfirmed Positive HIV PCR Test Results among African Infants with HIV Exposure in the International epidemiology Databases to Evaluate AIDS (IeDEA) Consortium.

In a large, multi-regional cohort of African infants with HIV exposure, 44% of those with a positive HIV PCR lacked a confirmatory positive test. Efforts are needed to ensure high-fidelity implementation of HIV testing algorithms, so that all positive results are confirmed thereby reducing the risk of potentially false-positive results.

Long-term HIV care outcomes under universal HIV treatment guidelines: A retrospective cohort study in 25 countries.

BACKGROUND: While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. METHODS AND FINDINGS: For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with ≥12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. CONCLUSIONS: In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality.

The Effect of HIV Treatment Interruption on Subsequent Immunological Response.

Recovery of CD4-positive T lymphocyte count after initiation of antiretroviral therapy (ART) has been thoroughly examined among people with human immunodeficiency virus infection. However, immunological response after restart of ART following care interruption is less well studied. We compared CD4 cell-count trends before disengagement from care and after ART reinitiation. Data were obtained from the East Africa International Epidemiology Databases to Evaluate AIDS (IeDEA) Collaboration (2001-2011; n = 62,534). CD4 cell-count trends before disengagement, during disengagement, and after ART reinitiation were simultaneously estimated through a linear mixed model with 2 subject-specific knots placed at the times of disengagement and treatment reinitiation. We also estimated CD4 trends conditional on the baseline CD4 value. A total of 10,961 patients returned to care after disengagement from care, with the median gap in care being 2.7 (interquartile range, 2.1-5.4) months. Our model showed that CD4 cell-count increases after ART reinitiation were much slower than those before disengagement. Assuming that disengagement from care occurred 12 months after ART initiation and a 3-month treatment gap, CD4 counts measured at 3 years since ART initiation would be lower by 36.5 cells/µL than those obtained under no disengagement. Given that poorer CD4 restoration is associated with increased mortality/morbidity, specific interventions targeted at better retention in care are urgently required.

Relating CYP2B6 genotype and efavirenz resistance among post-partum women living with HIV with high viremia in Uganda: a nested cross-sectional study.

BACKGROUND: We investigated the association between CYP2B6 polymorphisms and efavirenz drug resistance among women living with HIV who started on antiretroviral therapy during pregnancy and with high viremia during post-partum. METHODS: This was a cross-sectional study of women with viral loads greater than 1000 copies/ml who were at least 6 weeks postpartum. Sanger sequencing was used to detect resistant mutations, as well as host genotyping, and efavirenz resistance was compared among the metabolizer genotypes. RESULTS: Over the course of one year (July 2017-July 2018), 322 women were screened, with 110 (34.2%) having viral loads of 1000 copies/ml and 62 having whole blood available for genotyping. Fifty-nine of these women had both viral resistance and human host genotypic results. Efavirenz resistance according to metabolizer genotype was; 47% in slow, 34% in extensive and 28% in intermediate metabolizers, but the difference was not statistically significant due to the small sample size. CONCLUSIONS: There was no statistically significant difference in EFV resistance between EFV metabolizer genotypes in women who started antiretroviral therapy during pregnancy and had high viremia in the postpartum period. However, a numerical trend was discovered, which calls for confirmation in a large, well-designed, statistically powered study.

Disparities in Dolutegravir Uptake Affecting Females of Reproductive Age With HIV in Low- and Middle-Income Countries After Initial Concerns About Teratogenicity : An Observational Study.

BACKGROUND: The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE: To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN: Observational cohort study. SETTING: 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS: 134 672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS: Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS: Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION: Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION: Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE: National Institutes of Health.

Viral Load Status Before Switching to Dolutegravir-Containing Antiretroviral Therapy and Associations With Human Immunodeficiency Virus Treatment Outcomes in Sub-Saharan Africa.

BACKGROUND: Dolutegravir is being rolled out globally as part of preferred antiretroviral therapy (ART) regimens, including among treatment-experienced patients. The role of viral load (VL) testing before switching patients already on ART to a dolutegravir-containing regimen is less clear in real-world settings. METHODS: We included patients from the International epidemiology Databases to Evaluate AIDS consortium who switched from a nevirapine- or efavirenz-containing regimen to one with dolutegravir. We used multivariable cause-specific hazards regression to estimate the association of the most recent VL test in the 12 months before switching with subsequent outcomes. RESULTS: We included 36 393 patients at 37 sites in 5 countries (Democratic Republic of the Congo, Kenya, Rwanda, Tanzania, Uganda) who switched to dolutegravir from July 2017 through February 2020, with a median follow-up of approximately 11 months. Compared with those who switched with a VL <200 copies/mL, patients without a recent VL test or with a preswitch VL ≥1000 copies/mL had significantly increased hazards of an incident VL ≥1000 copies/mL (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.99-4.19 and aHR, 6.60; 95% CI, 4.36-9.99, respectively) and pulmonary tuberculosis or a World Health Organization clinical stage 4 event (aHR, 4.78; 95% CI, 2.77-8.24 and aHR, 13.97; 95% CI, 6.62-29.50, respectively). CONCLUSIONS: A VL test before switching to dolutegravir may help identify patients who need additional clinical monitoring and/or adherence support. Further surveillance of patients who switched to dolutegravir with an unknown or unsuppressed VL is needed.

Clinical and programmatic outcomes of HIV-exposed infants enrolled in care at geographically diverse clinics, 1997-2021: A cohort study.

BACKGROUND: Although 1·3 million women with HIV give birth annually, care and outcomes for HIV-exposed infants remain incompletely understood. We analyzed programmatic and health indicators in a large, multidecade global dataset of linked mother-infant records from clinics and programs associated with the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS AND FINDINGS: HIV-exposed infants were eligible for this retrospective cohort analysis if enrolled at <18 months at 198 clinics in 10 countries across 5 IeDEA regions: East Africa (EA), Central Africa (CA), West Africa (WA), Southern Africa (SA), and the Caribbean, Central, and South America network (CCASAnet). We estimated cumulative incidences of DNA PCR testing, loss to follow-up (LTFU), HIV diagnosis, and death through 24 months of age using proportional subdistribution hazard models accounting for competing risks. Competing risks were transfer, care withdrawal, and confirmation of negative HIV status, along with LTFU and death, when not the outcome of interest. In CA and EA, we quantified associations between maternal/infant characteristics and each outcome. A total of 82,067 infants (47,300 EA, 10,699 CA, 6,503 WA, 15,770 SA, 1,795 CCASAnet) born from 1997 to 2021 were included. Maternal antiretroviral therapy (ART) use during pregnancy ranged from 65·6% (CCASAnet) to 89·5% (EA), with improvements in all regions over time. Twenty-four-month cumulative incidences varied widely across regions, ranging from 12·3% (95% confidence limit [CL], 11·2%,13·5%) in WA to 94·8% (95% CL, 94·6%,95·1%) in EA for DNA PCR testing; 56·2% (95% CL, 55·2%,57·1%) in EA to 98·5% (95% CL, 98·3%,98·7%) in WA for LTFU; 1·9% (95% CL, 1·6%,2·3%) in WA to 10·3% (95% CL, 9·7%,10·9%) in EA for HIV diagnosis; and 0·5% (95% CL, 0·2%,1·0%) in CCASAnet to 4·7% (95% CL, 4·4%,5·0%) in EA for death. Although infant retention did not improve, HIV diagnosis and death decreased over time, and in EA, the cumulative incidence of HIV diagnosis decreased substantially, declining to 2·9% (95% CL, 1·5%,5·4%) in 2020. Maternal ART was associated with decreased infant mortality (subdistribution hazard ratio [sdHR], 0·65; 95% CL, 0·47,0·91 in EA, and sdHR, 0·51; 95% CL, 0·36,0·74 in CA) and HIV diagnosis (sdHR, 0·40; 95% CL, 0·31,0·50 in EA, and sdHR, 0·41; 95% CL, 0·31,0·54 in CA). Study limitations include potential misclassification of outcomes in real-world service delivery data and possible nonrepresentativeness of IeDEA sites and the population of HIV-exposed infants they serve. CONCLUSIONS: While there was marked regional and temporal heterogeneity in clinical and programmatic outcomes, infant LTFU was high across all regions and time periods. Further efforts are needed to keep HIV-exposed infants in care to receive essential services to reduce HIV infection and mortality.

Retention in care and viral suppression in the PMTCT continuum at a large referral facility in western Kenya.

Medical records of pregnant and postpartum women living with HIV and their infants attending a large referral facility in Kenya from 2015 to 2019 were analyzed to identify characteristics associated with retention in care and viral suppression. Women were stratified based on the timing of HIV care enrollment: known HIV-positive (KHP; enrolled pre-pregnancy) and newly HIV-positive (NHP; enrolled during pregnancy). Associations with retention at 18 months postpartum and viral suppression (< 1000 copies/mL) were determined. Among 856 women (20% NHP), retention was 83% for KHPs and 53% for NHPs. Viral suppression was 88% for KHPs and 93% for NHPs, but 19% of women were missing viral load results. In a competing risk model, viral suppression increased by 18% for each additional year of age but was not associated with other factors. Overall, 1.9% of 698 infants with ≥ 1 HIV test result were HIV-positive. Tailored interventions are needed to promote retention and viral load testing, particularly for NHPs, in the PMTCT continuum.

"I have never talked to anyone to free my mind" - challenges surrounding status disclosure to adolescents contribute to their disengagement from HIV care: a qualitative study in western Kenya.

INTRODUCTION: Adolescents living with HIV (ALHIV, ages 10-19) experience complex barriers to care engagement. Challenges surrounding HIV status disclosure or non-disclosure to adolescents may contribute to adolescent disengagement from HIV care or non-adherence to ART. We performed a qualitative study to investigate the contribution of disclosure challenges to adolescent disengagement from HIV care. METHODS: This was a qualitative study performed with disengaged ALHIV and their caregivers, and with healthcare workers (HCW) in the Academic Model Providing Access to Healthcare (AMPATH) program in western Kenya. Inclusion criteria for ALHIV were ≥1 visit within the 18 months prior to data collection at one of two clinical sites and nonattendance ≥60 days following their last scheduled appointment. HCW were recruited from 10 clinics. Analysis was conducted by multiple independent coders, and narratives of disclosure and care disengagement were closely interrogated. Overarching themes were elucidated and summarized. RESULTS: Interviews were conducted with 42 disengaged ALHIV, 32 caregivers, and 28 HCW. ALHIV were average age 17.0 (range 12.9-20.9), and 95% indicated awareness of their HIV diagnosis. Issues surrounding disclosure to ALHIV presented important barriers to HIV care engagement. Themes centered on delays in HIV status disclosure; hesitancy and reluctance among caregivers to disclose; struggles for adolescents to cope with feelings of having been deceived prior to full disclosure; pervasive HIV stigma internalized in school and community settings prior to disclosure; and inadequate and unstructured support after disclosure, including for adolescent mental health burdens and for adolescent-caregiver relationships and communication. Both HCW and caregivers described feeling inadequately prepared to optimally handle disclosure and to manage challenges that may arise after disclosure. CONCLUSIONS: Complex challenges surrounding HIV status disclosure to adolescents contribute to care disengagement. There is need to enhance training and resources for HCW, and to empower caregivers to support children and adolescents before, during, and after HIV status disclosure. This should include counseling caregivers on how to provide children with developmentally-appropriate and accurate information about their health from an early age, and to support adolescent-caregiver communication and relationships. Optimally integrating peer support can further promote ALHIV wellbeing and retention in care.

Effects of National Adoption of Treat-All Guidelines on Pre-Antiretroviral Therapy (ART) CD4 Testing and Viral Load Monitoring After ART initiation: A Regression Discontinuity Analysis.

BACKGROUND: The World Health Organization's Treat-All guidance recommends CD4 testing before initiating antiretroviral therapy (ART), and routine viral load (VL) monitoring (over CD4 monitoring) for patients on ART. METHODS: We used regression discontinuity analyses to estimate changes in CD4 testing and VL monitoring among 547 837 ART-naive patients enrolling in human immunodeficiency virus (HIV) care during 2006-2018 at 225 clinics in 26 countries where Treat-All policies were adopted. We examined CD4 testing within 12 months before and VL monitoring 6 months after ART initiation among adults (≥20 years), adolescents (10-19 years), and children (0-9 years) in low/lower-middle-income countries (L/LMICs) and high/upper-middle-income countries (H/UMICs). RESULTS: Treat-All adoption led to an immediate decrease in pre-ART CD4 testing among adults in L/LMICs, from 57.0% to 48.1% (-8.9 percentage points [pp]; 95% CI: -11.0, -6.8), and a small increase in H/UMICs, from 90.1% to 91.7% (+1.6pp; 95% CI: 0.2, 3.0), with no changes among adolescents or children; decreases in pre-ART CD4 testing accelerated after Treat-All adoption in L/LMICs. In L/LMICs, VL monitoring after ART initiation was low among all patients in L/LMICs before Treat-All; while there was no immediate change at Treat-All adoption, VL monitoring trends significantly increased afterwards. VL monitoring increased among adults immediately after Treat-All adoption, from 58.2% to 61.1% (+2.9pp; 95% CI: 0.5, 5.4), with no significant changes among adolescents/children. CONCLUSIONS: While on-ART VL monitoring has improved in L/LMICs, Treat-All adoption has accelerated and disparately worsened suboptimal pre-ART CD4 monitoring, which may compromise care outcomes for individuals with advanced HIV.

Pregnancies among women living with HIV using contraceptives and antiretroviral therapy in western Kenya: a retrospective, cohort study.

BACKGROUND: Preventing unintended pregnancies is paramount for women living with HIV (WLHIV). Previous studies have suggested that efavirenz-containing antiretroviral therapy (ART) reduces contraceptive effectiveness of implants, but there are uncertainties regarding the quality of the electronic medical record (EMR) data used in these prior studies. METHODS: We conducted a retrospective, cohort study of EMR data from 2011 to 2015 among WLHIV of reproductive age accessing HIV care in public facilities in western Kenya. We validated a large subsample of records with manual chart review and telephone interviews. We estimated adjusted incidence rate ratios (aIRRs) with Poisson regression accounting for the validation sampling using inverse probability weighting and generalized raking. RESULTS: A total of 85,324 women contributed a total of 170,845 women-years (w-y) of observation time; a subset of 5080 women had their charts reviewed, and 1285 underwent interviews. Among implant users, the aIRR of pregnancy for efavirenz- vs. nevirapine-containing ART was 1.9 (95% CI 1.6, 2.4) using EMR data only and 3.2 (95% CI 1.8, 5.7) when additionally using both chart review and interview validated data. Among efavirenz users, the aIRR of pregnancy for depomedroxyprogesterone acetate (DMPA) vs. implant use was 1.8 (95% CI 1.5, 2.1) in EMR only and 2.4 (95% CI 1.0, 6.1) using validated data. CONCLUSION: Pregnancy rates are higher when contraceptive implants are concomitantly used with efavirenz-containing ART, though rates were similar to leading alternative contraceptive methods such as DMPA. Our data provides policymakers, program staff, and WLHIV greater confidence in guiding their decision-making around contraceptive and ART options. Our novel, 3-phase validation sampling provides an innovative tool for using routine EMR data to improve the robustness of data quality.

Association of Health Status and Nicotine Consumption with SARS-CoV-2 positivity rates.

BACKGROUND: Much of what is known about COVID-19 risk factors comes from patients with serious symptoms who test positive. While risk factors for hospitalization or death include chronic conditions and smoking; less is known about how health status or nicotine consumption is associated with risk of SARS-CoV-2 infection among individuals who do not present clinically. METHODS: Two community-based population samples (including individuals randomly and nonrandomly selected for statewide testing, n = 8214) underwent SARS-CoV-2 testing in nonclinical settings. Each participant was tested for current (viral PCR) and past (antibody) infection in either April or June of 2020. Before testing, participants provided demographic information and self-reported health status and nicotine and tobacco behaviors (smoking, chewing, vaping/e-cigarettes). Using descriptive statistics and a bivariate logistic regression model, we examined the association between health status and use of tobacco or nicotine with SARS-CoV-2 positivity on either PCR or antibody tests. RESULTS: Compared to people with self-identified "excellent" or very good health status, those reporting "good" or "fair" health status had a higher risk of past or current infections. Positive smoking status was inversely associated with SARS-CoV-2 infection. Chewing tobacco was associated with infection and the use of vaping/e-cigarettes was not associated with infection. CONCLUSIONS: In a statewide, community-based population drawn for SARS-CoV-2 testing, we find that overall health status was associated with infection rates. Unlike in studies of COVID-19 patients, smoking status was inversely associated with SARS-CoV-2 positivity. More research is needed to further understand the nature of this relationship.

FIRST- LINE ANTIRETROVIRAL TREATMENT FAILURE IN EAST AFRICAN CHILDREN.

Objectives: To describe the incidence of antiretroviral treatment failure and associated factors in a pediatric clinical cohort within the East African International epidemiology Databases to Evaluate AIDS (EA-IeDEA) consortium. Design: A retrospective cohort study. Clinical treatment failure was defined as advancement in clinical WHO stage, or CDC class at least 24 weeks after initiation of treatment. Immunological failure was defined as developing or returning to the following age-related immunological thresholds after at least 24 weeks on treatment; CD4 count of <200 or CD4%<10% for children aged 2-5 years and CD4 count of < 100 for a child aged > 5years. Setting: The study utilized the electronic medical records of HIV-infected pediatric patients enrolled into the EA-IeDEA consortium clinics from January 2005 to August 2012. Results: A total of 5927 children were included in the analysis. The estimated cumulative incidence of clinical ART treatment failure at one year and four years post ART initiation was11.5% and 31% respectively, while that of immunological treatment failure was at 3% and 22.5% respectively. The main factors associated with clinical failure were advanced clinical stage at ART-initiation, year started ART and residing in a rural area. Factors associated with immunological failure were male gender and age of the child at ART-initiation. Only 6% of those identified as having clinical treatment failure were switched to second line treatment during the four years of follow-up. Conclusion: The probability of clinical and immunologic failure was relatively high and increased with time.

How Many SARS-CoV-2-Infected People Require Hospitalization? Using Random Sample Testing to Better Inform Preparedness Efforts.

CONTEXT: Existing hospitalization ratios for COVID-19 typically use case counts in the denominator, which problematically underestimates total infections because asymptomatic and mildly infected persons rarely get tested. As a result, surge models that rely on case counts to forecast hospital demand may be inaccurately influencing policy and decision-maker action. OBJECTIVE: Based on SARS-CoV-2 prevalence data derived from a statewide random sample (as opposed to relying on reported case counts), we determine the infection-hospitalization ratio (IHR), defined as the percentage of infected individuals who are hospitalized, for various demographic groups in Indiana. Furthermore, for comparison, we show the extent to which case-based hospitalization ratios, compared with the IHR, overestimate the probability of hospitalization by demographic group. DESIGN: Secondary analysis of statewide prevalence data from Indiana, COVID-19 hospitalization data extracted from a statewide health information exchange, and all reported COVID-19 cases to the state health department. SETTING: State of Indiana as of April 30, 2020. MAIN OUTCOME MEASURES: Demographic-stratified IHRs and case-hospitalization ratios. RESULTS: The overall IHR was 2.1% and varied more by age than by race or sex. Infection-hospitalization ratio estimates ranged from 0.4% for those younger than 40 years to 9.2% for those older than 60 years. Hospitalization rates based on case counts overestimated the IHR by a factor of 10, but this overestimation differed by demographic groups, especially age. CONCLUSIONS: In this first study of the IHR based on population prevalence, our results can improve forecasting models of hospital demand-especially in preparation for the upcoming winter period when an increase in SARS CoV-2 infections is expected.

Impact of Universal Antiretroviral Treatment Eligibility on Rapid Treatment Initiation Among Young Adolescents with Human Immunodeficiency Virus in Sub-Saharan Africa.

BACKGROUND: Young adolescents with perinatally acquired human immunodeficiency virus (HIV) are at risk for poor care outcomes. We examined whether universal antiretroviral treatment (ART) eligibility policies (Treat All) improved rapid ART initiation after care enrollment among 10-14-year-olds in 7 sub-Saharan African countries. METHODS: Regression discontinuity analysis and data for 6912 patients aged 10-14-years were used to estimate changes in rapid ART initiation (within 30 days of care enrollment) after adoption of Treat All policies in 2 groups of countries: Uganda and Zambia (policy adopted in 2013) and Burundi, Democratic Republic of the Congo, Kenya, Malawi, and Rwanda (policy adopted in 2016). RESULTS: There were immediate increases in rapid ART initiation among young adolescents after national adoption of Treat All. Increases were greater in countries adopting the policy in 2016 than in those adopting it in 2013: 23.4 percentage points (pp) (95% confidence interval, 13.9-32.8) versus 11.2pp (2.5-19.9). However, the rate of increase in rapid ART initiation among 10-14-year-olds rose appreciably in countries with earlier treatment expansions, from 1.5pp per year before Treat All to 7.7pp per year afterward. CONCLUSIONS: Universal ART eligibility has increased rapid treatment initiation among young adolescents enrolling in HIV care. Further research should assess their retention in care and viral suppression under Treat All.

Real-world use of chemotherapy for Kaposi's sarcoma in a large community-based HIV primary care system in Kenya.

BACKGROUND: Kaposi's sarcoma (KS) is one of the most common HIV-associated malignancies in sub-Saharan Africa. Worldwide, the availability of antiretroviral therapy (ART) has improved KS survival. In resource-rich settings, survival has also benefited from chemotherapy, which is widely available. Little is known, however, about the epidemiology of chemotherapy use for HIV-associated KS in resource-limited regions such as sub-Saharan Africa. METHODS: We identified all patients newly diagnosed with HIV-related KS from 2009 to 2012 in the 26-clinic AMPATH network, a large community-based care network in Kenya. We ascertained disease severity at diagnosis, frequency of initiation of chemotherapy, and distribution of chemotherapeutic regimens used. Indications for chemotherapy included AIDS Clinical Trial Group T1 stage and/or "severe" disease defined by WHO KS treatment guidelines. RESULTS: Of 674 patients diagnosed with KS, charts were available for 588; 61% were men, median age was 35 years, and median CD4 at KS diagnosis was 185 cells/µl. At time of diagnosis, 58% had at least one chemotherapy indication, and 22% had more than one indication. For patients with a chemotherapy indication, cumulative incidence of chemotherapy initiation (with death as a competing event) was 37% by 1 month and 56% by 1 year. Median time from diagnosis to chemotherapy initiation was 25 days (IQR 1-50 days). In multivariable regression, patients with > 3 chemotherapy indications at time of diagnosis had a 2.30 (95% CI 1.46-3.60) increased risk of rapid chemotherapy initiation (within 30 days of diagnosis) compared to those with only one chemotherapy indication (p < 0.001). Initial regimens were bleomycin-vincristine (78%), adriamycin-bleomycin-vincristine (11%), etoposide (7%), and gemcitabine (4%). CONCLUSIONS: A substantial fraction of patients with KS in East Africa are diagnosed at advanced disease stage. For patients with chemotherapy indications, nearly half did not receive chemotherapy by one year. Liposomal anthracyclines, often used in resource-rich settings, were not first line. These findings emphasize challenges in East Africa cancer care, and highlight the need for further advocacy for improved access to higher quality chemotherapy in this setting.

Population Point Prevalence of SARS-CoV-2 Infection Based on a Statewide Random Sample - Indiana, April 25-29, 2020.

Population prevalence of persons infected with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), varies by subpopulation and locality. U.S. studies of SARS-CoV-2 infection have examined infections in nonrandom samples (1) or seroprevalence in specific populations* (2), which are limited in their generalizability and cannot be used to accurately calculate infection-fatality rates. During April 25-29, 2020, Indiana conducted statewide random sample testing of persons aged ≥12 years to assess prevalence of active infection and presence of antibodies to SARS-CoV-2; additional nonrandom sampling was conducted in racial and ethnic minority communities to better understand the impact of the virus in certain racial and ethnic minority populations. Estimates were adjusted for nonresponse to reflect state demographics using an iterative proportional fitting method. Among 3,658 noninstitutionalized participants in the random sample survey, the estimated statewide point prevalence of active SARS-CoV-2 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing was 1.74% (95% confidence interval [CI] = 1.10-2.54); 44.2% of these persons reported no symptoms during the 2 weeks before testing. The prevalence of immunoglobulin G (IgG) seropositivity, indicating past infection, was 1.09% (95% CI = 0.76-1.45). The overall prevalence of current and previous infections of SARS-CoV-2 in Indiana was 2.79% (95% CI = 2.02-3.70). In the random sample, higher overall prevalences were observed among Hispanics and those who reported having a household contact who had previously been told by a health care provider that they had COVID-19. By late April, an estimated 187,802 Indiana residents were currently or previously infected with SARS-CoV-2 (9.6 times higher than the number of confirmed cases [17,792]) (3), and 1,099 residents died (infection-fatality ratio = 0.58%). The number of reported cases represents only a fraction of the estimated total number of infections. Given the large number of persons who remain susceptible in Indiana, adherence to evidence-based public health mitigation and containment measures (e.g., social distancing, consistent and correct use of face coverings, and hand hygiene) is needed to reduce surge in hospitalizations and prevent morbidity and mortality from COVID-19.

Changes in rapid HIV treatment initiation after national "treat all" policy adoption in 6 sub-Saharan African countries: Regression discontinuity analysis.

BACKGROUND: Most countries have formally adopted the World Health Organization's 2015 recommendation of universal HIV treatment ("treat all"). However, there are few rigorous assessments of the real-world impact of treat all policies on antiretroviral treatment (ART) uptake across different contexts. METHODS AND FINDINGS: We used longitudinal data for 814,603 patients enrolling in HIV care between 1 January 2004 and 10 July 2018 in 6 countries participating in the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium: Burundi (N = 11,176), Kenya (N = 179,941), Malawi (N = 84,558), Rwanda (N = 17,396), Uganda (N = 96,286), and Zambia (N = 425,246). Using a quasi-experimental regression discontinuity design, we assessed the change in the proportion initiating ART within 30 days of enrollment in HIV care (rapid ART initiation) after country-level adoption of the treat all policy. A modified Poisson model was used to identify factors associated with failure to initiate ART rapidly under treat all. In each of the 6 countries, over 60% of included patients were female, and median age at enrollment ranged from 32 to 36 years. In all countries studied, national adoption of treat all was associated with large increases in rapid ART initiation. Significant increases in rapid ART initiation immediately after treat all policy adoption were observed in Rwanda, from 44.4% to 78.9% of patients (34.5 percentage points [pp], 95% CI 27.2 to 41.7; p < 0.001), Kenya (25.7 pp, 95% CI 21.8 to 29.5; p < 0.001), Burundi (17.7 pp, 95% CI 6.5 to 28.9; p = 0.002), and Malawi (12.5 pp, 95% CI 7.5 to 17.5; p < 0.001), while no immediate increase was observed in Zambia (0.4 pp, 95% CI -2.9 to 3.8; p = 0.804) and Uganda (-4.2 pp, 95% CI -9.0 to 0.7; p = 0.090). The rate of rapid ART initiation accelerated sharply following treat all policy adoption in Malawi, Uganda, and Zambia; slowed in Kenya; and did not change in Rwanda and Burundi. In post hoc analyses restricted to patients enrolling under treat all, young adults (16-24 years) and men were at increased risk of not rapidly initiating ART (compared to older patients and women, respectively). However, rapid ART initiation following enrollment increased for all groups as more time elapsed since treat all policy adoption. Study limitations include incomplete data on potential ART eligibility criteria, such as clinical status, pregnancy, and enrollment CD4 count, which precluded the assessment of rapid ART initiation specifically among patients known to be eligible for ART before treat all. CONCLUSIONS: Our analysis indicates that adoption of treat all policies had a strong effect on increasing rates of rapid ART initiation, and that these increases followed different trajectories across the 6 countries. Young adults and men still require additional attention to further improve rapid ART initiation.

HIV treatment eligibility expansion and timely antiretroviral treatment initiation following enrollment in HIV care: A metaregression analysis of programmatic data from 22 countries.

BACKGROUND: The effect of antiretroviral treatment (ART) eligibility expansions on patient outcomes, including rates of timely ART initiation among those enrolling in care, has not been assessed on a large scale. In addition, it is not known whether ART eligibility expansions may lead to "crowding out" of sicker patients. METHODS AND FINDINGS: We examined changes in timely ART initiation (within 6 months) at the original site of HIV care enrollment after ART eligibility expansions among 284,740 adult ART-naïve patients at 171 International Epidemiology Databases to Evaluate AIDS (IeDEA) network sites in 22 countries where national policies expanding ART eligibility were introduced between 2007 and 2015. Half of the sites included in this analysis were from Southern Africa, one-third were from East Africa, and the remainder were from the Asia-Pacific, Central Africa, North America, and South and Central America regions. The median age of patients enrolling in care at contributing sites was 33.5 years, and the median percentage of female patients at these clinics was 62.5%. We assessed the 6-month cumulative incidence of timely ART initiation (CI-ART) before and after major expansions of ART eligibility (i.e., expansion to treat persons with CD4 ≤ 350 cells/µL [145 sites in 22 countries] and CD4 ≤ 500 cells/µL [152 sites in 15 countries]). Random effects metaregression models were used to estimate absolute changes in CI-ART at each site before and after guideline expansion. The crude pooled estimate of change in CI-ART was 4.3 percentage points (95% confidence interval [CI] 2.6 to 6.1) after ART eligibility expansion to CD4 ≤ 350, from a baseline median CI-ART of 53%; and 15.9 percentage points (pp) (95% CI 14.3 to 17.4) after ART eligibility expansion to CD4 ≤ 500, from a baseline median CI-ART of 57%. The largest increases in CI-ART were observed among those newly eligible for treatment (18.2 pp after expansion to CD4 ≤ 350 and 47.4 pp after expansion to CD4 ≤ 500), with no change or small increases among those eligible under prior guidelines (CD4 ≤ 350: -0.6 pp, 95% CI -2.0 to 0.7 pp; CD4 ≤ 500: 4.9 pp, 95% CI 3.3 to 6.5 pp). For ART eligibility expansion to CD4 ≤ 500, changes in CI-ART were largest among younger patients (16-24 years: 21.5 pp, 95% CI 18.9 to 24.2 pp). Key limitations include the lack of a counterfactual and difficulty accounting for secular outcome trends, due to universal exposure to guideline changes in each country. CONCLUSIONS: These findings underscore the potential of ART eligibility expansion to improve the timeliness of ART initiation globally, particularly for young adults.

Access to antiretroviral therapy in HIV-infected children aged 0-19 years in the International Epidemiology Databases to Evaluate AIDS (IeDEA) Global Cohort Consortium, 2004-2015: A prospective cohort study.

INTRODUCTION: Access to antiretroviral therapy (ART) is a global priority. However, the attrition across the continuum of care for HIV-infected children between their HIV diagnosis and ART initiation is not well known. We analyzed the time from enrollment into HIV care to ART initiation in HIV-infected children within the International Epidemiology Databases to Evaluate AIDS (IeDEA) Global Cohort Consortium. METHODS AND FINDINGS: We included 135,479 HIV-1-infected children, aged 0-19 years and ART-naïve at enrollment, between 1 January 2004 and 31 December 2015, in IeDEA cohorts from Central Africa (3 countries; n = 4,948), East Africa (3 countries; n = 22,827), West Africa (7 countries; n = 7,372), Southern Africa (6 countries; n = 93,799), Asia-Pacific (6 countries; n = 4,045), and Latin America (7 countries; n = 2,488). Follow-up in these cohorts is typically every 3-6 months. We described time to ART initiation and missed opportunities (death or loss to follow-up [LTFU]: last clinical visit >6 months) since baseline (the date of HIV diagnosis or, if unavailable, date of enrollment). Cumulative incidence functions (CIFs) for and determinants of ART initiation were computed, with death and LTFU as competing risks. Among the 135,479 children included, 99,404 (73.4%) initiated ART, 1.9% died, 1.4% were transferred out, and 20.4% were lost to follow-up before ART initiation. The 24-month CIF for ART initiation was 68.2% (95% CI: 67.9%-68.4%); it was lower in sub-Saharan Africa-ranging from 49.8% (95% CI: 48.4%-51.2%) in Central Africa to 72.5% (95% CI: 71.5%-73.5%) in West Africa-compared to Latin America (71.0%, 95% CI: 69.1%-72.7%) and the Asia-Pacific (78.3%, 95% CI: 76.9%-79.6%). Adolescents aged 15-19 years and infants <1 year had the lowest cumulative incidence of ART initiation compared to other ages: 62.2% (95% CI: 61.6%-62.8%) and 66.4% (95% CI: 65.7%-67.0%), respectively. Overall, 49.1% were ART-eligible per local guidelines at baseline, of whom 80.6% initiated ART. The following children had lower cumulative incidence of ART initiation: female children (p < 0.01); those aged <1 year, 2-4 years, 5-9 years, and 15-19 years (versus those aged 10-14 years, p < 0.01); those who became eligible during follow-up (versus eligible at enrollment, p < 0.01); and those receiving care in low-income or lower-middle-income countries (p < 0.01). The main limitations of our study include left truncation and survivor bias, caused by deaths of children prior to enrollment, and use of enrollment date as a proxy for missing data on date of HIV diagnosis, which could have led to underestimation of the time between HIV diagnosis and ART initiation. CONCLUSIONS: In this study, 68% of HIV-infected children initiated ART by 24 months. However, there was a substantial risk of LTFU before ART initiation, which may also represent undocumented mortality. In 2015, many obstacles to ART initiation remained, with substantial inequities. More effective and targeted interventions to improve access are needed to reach the target of treating 90% of HIV-infected children with ART.