HIV risk behaviour, viraemia, and transmission across HIV cascade stages including low-level viremia: Analysis of 14 cross-sectional population-based HIV Impact Assessment surveys in sub-Saharan Africa.

As antiretroviral treatment (ART) coverage for people living with HIV (PLHIV) increases, HIV programmes require up-to-date information about evolving HIV risk behaviour and transmission risk, including those with low-level viremia (LLV; >50 to ≤1000 copies/mL), to guide prevention priorities. We aimed to assess differences in sexual risk behaviours, distribution of viral load (VL) and proportion of transmission across PLHIV subgroups. We analysed data from Population-based HIV Impact Assessment surveys in 14 sub-Saharan African countries during 2015-2019. We estimated adjusted prevalence ratios (aPR) of self-reported HIV high-risk behaviour (multiple partners and condomless sex) across cascade stages via generalised estimation equations. We modelled the proportions of transmission from each subgroup using relative self-reported sexual risk, a Hill function for transmission rate by VL, and proportions within cascade stages from surveys and UNAIDS country estimates for 2010-2020. Compared to PLHIV with undetectable VL (≤50 copies/mL), undiagnosed PLHIV (aPR women: 1.28 [95% CI: 1.08-1.52]; men: 1.61 [1.33-1.95]) and men diagnosed but untreated (2.06 [1.52-2.78]) were more likely to self-report high-risk sex. High-risk behaviour was not significantly associated with LLV. Mean VL was similar among undiagnosed, diagnosed but untreated, and on ART but non-suppressed sub-groups. Across surveys, undiagnosed and diagnosed but untreated contributed most to transmission (40-91% and 1-41%, respectively), with less than 1% from those with LLV. Between 2010 and 2020, the proportion of transmission from individuals on ART but non-suppressed increased. In settings with high ART coverage, effective HIV testing, ART linkage, and retention remain priorities to reduce HIV transmission. Persons with LLV are an increasing share of PLHIV but their contribution to HIV transmission was small. Improving suppression among PLHIV on ART with VL ≥1000 copies/mL will become increasingly important.

Progress towards the UNAIDS 95-95-95 targets in the Fifth Botswana AIDS Impact Survey (BAIS V 2021): a nationally representative survey.

BACKGROUND: In 2014, UNAIDS set a goal to end the AIDS epidemic by achieving targets for the percentage of people living with HIV who were aware of their status, on antiretroviral therapy (ART), and virally suppressed. In 2020, these targets were revised to 95% for each measure (known as 95-95-95), to be reached among people living with HIV by 2025. We used data from the Fifth Botswana AIDS Impact Survey (BAIS V) to measure progress towards these testing and treatment targets in Botswana. METHODS: BAIS V used a two-stage cluster design to obtain a nationally representative sample of people aged 15-64 years in Botswana. During March-August, 2021, 14 763 consenting participants were interviewed and tested for HIV in their households by survey teams. HIV-positive specimens were tested for viral load, presence of antiretroviral drugs, and recency of infection using the HIV-1 limiting antigen avidity enzyme immunoassay. Estimates of HIV-positive status and use of ART were based on self-report and the analysis of blood specimens for antiretroviral drugs. Viral load suppression was defined as an HIV RNA concentration of less than 1000 copies per mL. HIV incidence was calculated using the recent infection testing algorithm. Data were weighted to account for the complex survey design. FINDINGS: The national HIV prevalence in Botswana among people aged 15-64 years was 20·8% and the annual incidence of HIV infection was 0·2%. 95·1% (men 93·0%, women 96·4%) of people living with HIV aged 15-64 years were aware of their status, 98·0% (men 97·2%, women 98·4%) of those aware were on ART, and 97·9% (men 96·6%, women 98·6%) of those on ART had viral load suppression. Among young people (aged 15-24 years) living with HIV, 84·5% were aware of their status, 98·5% of those aware were on ART, and 91·6% of those on ART had viral load suppression. The prevalance of viral load suppression among all people living with HIV was 91·8%, and varied by district-ranging from 85·3% in Gaborone to 100·0% in Selibe Phikwe. INTERPRETATION: BAIS V is the first population-based survey worldwide to report the achievement of the UNAIDS 95-95-95 goals, both overall and among women. Strategies to reach undiagnosed men and young people, including young women, are needed. FUNDING: US President's Emergency Plan for AIDS Relief.

Clozapine-laden carbon dots delivered to the brain via an intranasal pathway: Synthesis, characterization, ex vivo, and in vivo studies.

Clozapine, which is widely used to treat schizophrenia, shows low bioavailability due to poor solubility and high first-pass metabolism. The study aimed to design clozapine-loaded carbon dots (CDs) to enhance availability of the clozapine to the brain via intranasal pathway. The CDs were synthesized by pyrolysis of citric acid and urea at 200 °C by hydrothermal technique and characterized by photoluminescence, transmission electron microscopy (TEM), X-ray Photoelectron Spectrometer (XPS), and Fourier transform infrared spectrum (FTIR). The optimized clozapine-loaded CDs (CLZ-CDs-1:3-200) showed a quasi-spherical shape (9-12 nm) with stable blue fluorescence. The CDs showed high drug solubilization capacity (1.5 mg drug in 1 mg/ml CDs) with strong electrostatic interaction with clozapine (drug loading efficiency = 94.74%). The ex vivo release study performed using nasal goat mucosa showed sustained release of clozapine (43.89%) from CLZ-CDs-1:3-200 for 30 h. The ciliotoxicity study (histopathology) confirmed no toxicity to the nasal mucosal tissues using CDs. In the rat model (in vivo pharmacokinetic study), when CDs were administrated by the intranasal route, a significantly higher concentration of clozapine in the brain tissue (Cmax = 58.07 ± 5.36 µg/g and AUCt (µg/h*g) = 105.76 ± 12.31) was noted within a short time (tmax = 1 h) compared to clozapine suspension administered by intravenous route (Cmax = 20.99 ± 3.91 µg/g, AUC t (µg/h*g) = 56.89 ± 12.31, and tmax = 4 h). The high value of drug targeting efficiency (DTE, 486%) index and direct transport percentage (DTP, 58%) indicates the direct entry of clozapine-CDs in the brain via the olfactory route. In conclusion, designed CDs demonstrated a promising dosage form for targeted nose-to-brain delivery of clozapine for the effective treatment of schizophrenia.

Brief Report: Self-Reported HIV-Positive Status but Subsequent HIV-Negative Test Results in Population-Based HIV Impact Assessment Survey Participants-11 Sub-Saharan African Countries, 2015-2018.

BACKGROUND: HIV testing is a critical step to accessing antiretroviral therapy (ART) because early diagnosis can facilitate earlier initiation of ART. This study presents aggregated data of individuals who self-reported being HIV-positive but subsequently tested HIV-negative during nationally representative Population-Based HIV Impact Assessment surveys conducted in 11 countries from 2015 to 2018. METHOD: Survey participants aged 15 years or older were interviewed by trained personnel using a standard questionnaire to determine HIV testing history and self-reported HIV status. Home-based HIV testing and counseling using rapid diagnostic tests with return of results were performed by survey staff according to the respective national HIV testing services algorithms on venous blood samples. Laboratory-based confirmatory HIV testing for all participants identified as HIV-positives and self-reported positives, irrespective of HIV testing results, was conducted and included Geenius HIV-1/2 and DNA polymerase chain reaction if Geenius was negative or indeterminate. RESULTS: Of the 16,630 participants who self-reported as HIV-positive, 16,432 (98.6%) were confirmed as HIV-positive and 198 (1.4%) were HIV-negative by subsequent laboratory-based testing. Participants who self-reported as HIV-positive but tested HIV-negative were significantly younger than 30 years, less likely to have received ART, and less likely to have received a CD4 test compared with participants who self-reported as HIV-positive with laboratory-confirmed infection. CONCLUSIONS: A small proportion of self-reported HIV-positive individuals could not be confirmed as positive, which could be due to initial misdiagnosis, deliberate wrong self-report, or misunderstanding of the questionnaire. As universal ART access is expanding, it is increasingly important to ensure quality of HIV testing and confirmation of HIV diagnosis before ART initiation.

Comparison of HIV prevalence, incidence, and viral load suppression in Zambia population-based HIV impact assessments from 2016 and 2021.

BACKGROUND: The Zambian government has implemented a public health response to control the HIV epidemic in the country. Zambia conducted a population-based HIV impact assessment (ZAMPHIA) survey in 2021 to assess the status of the HIV epidemic to guide its public health programs. METHODS: ZAMPHIA 2021 was a cross-sectional two-stage cluster sample household survey among persons aged ≥15 years conducted in Zambia across all 10 provinces. Consenting participants were administered a standardized questionnaire and whole blood was tested for HIV according to national guidelines. HIV-1 viral load (VL), recent HIV infection, and antiretroviral medications were tested for in HIV-seropositive samples. Viral load suppression (VLS) was defined as <1000 copies/ml. ZAMPHIA 2021 results were compared to ZAMPHIA 2016 for persons aged 15-59 years (i.e., the overlapping age ranges). All estimates were weighted to account for nonresponse and survey design. RESULTS: During ZAMPHIA 2021, of 25 483 eligible persons aged ≥15 years, 18 804 (73.8%) were interviewed and tested for HIV. HIV prevalence was 11.0% and VLS prevalence was 86.2% overall, but was <80% among people living with HIV aged 15-24 years and in certain provinces. Among persons aged 15-59 years, from 2016 to 2021, HIV incidence declined from 0.6% to 0.3% ( P -value: 0.07) and VLS prevalence increased from 59.2% to 85.7% ( P -value: <0.01). DISCUSSION: Zambia has made substantial progress toward controlling the HIV epidemic from 2016 to 2021. Continued implementation of a test-and-treat strategy, with attention to groups with lower VLS in the ZAMPHIA 2021, could support reductions in HIV incidence and improve overall VLS in Zambia.

An experimental comparison of additional training in phoneme awareness, letter-sound knowledge and decoding for struggling beginner readers.

BACKGROUND: Despite evidence that synthetic phonics teaching has increased reading attainments, a sizable minority of children struggle to acquire phonics skills and teachers lack clear principles for deciding what types of additional support are most beneficial. Synthetic phonics teaches children to read using a decoding strategy to translate letters into sounds and blend them (e.g., c-a-t = "k - ae - t" = "cat"). To use a decoding strategy, children require letter-sound knowledge (LSK) and the ability to blend sound units (phonological awareness; PA). Training on PA has been shown to benefit struggling beginning readers. However, teachers in English primary schools do not routinely check PA. Instead, struggling beginner readers usually receive additional LSK support. AIMS: Until now, there has been no systematic comparison of the effectiveness of training on each component of the decoding process. Should additional support for struggling readers focus on improving PA, or on supplementary LSK and/or decoding instruction? We aim to increase understanding of the roles of LSK and PA in children's acquisition of phonics skills and uncover which types of additional training are most likely to be effective for struggling beginner readers. SAMPLE AND METHOD: We will compare training on each of these components, using a carefully controlled experimental design. We will identify reception-age children at risk of reading difficulties (target n = 225) and randomly allocate them to either PA, LSK or decoding (DEC) training. We will test whether training type influences post-test performance on word reading and whether any effects depend on participants' pre-test PA and/or LSK. RESULTS AND CONCLUSIONS: Two hundred and twenty-two participants completed the training. Planned analyses showed no effects of condition on word reading. However, exploratory analyses indicated that the advantage of trained over untrained words was significantly greater for the PA and DEC conditions. There was also a significantly greater improvement in PA for the DEC condition. Overall, our findings suggest a potential advantage of training that includes blending skills, particularly when decoding words that had been included in training. Future research is needed to develop a programme of training on blending skills combined with direct vocabulary instruction for struggling beginner readers.

Risk Factors for Recent HIV Infections among Adults in 14 Countries in Africa Identified by Population-Based HIV Impact Assessment Surveys, 2015-2019.

Identifying persons who have newly acquired HIV infections is critical for characterizing the HIV epidemic direction. We analyzed pooled data from nationally representative Population-Based HIV Impact Assessment surveys conducted across 14 countries in Africa for recent infection risk factors. We included adults 15-49 years of age who had sex during the previous year and used a recent infection testing algorithm to distinguish recent from long-term infections. We collected risk factor information via participant interviews and assessed correlates of recent infection using multinomial logistic regression, incorporating each survey's complex sampling design. Compared with HIV-negative persons, persons with higher odds of recent HIV infection were women, were divorced/separated/widowed, had multiple recent sex partners, had a recent HIV-positive sex partner or one with unknown status, and lived in communities with higher HIV viremia prevalence. Prevention programs focusing on persons at higher risk for HIV and their sexual partners will contribute to reducing HIV incidence.

Correction: Performance evaluation of the Asante Rapid Recency Assay for verification of HIV diagnosis and detection of recent HIV-1 infections: Implications for epidemic control.

[This corrects the article DOI: 10.1371/journal.pgph.0000316.].

Agreement on Interpretation of Point-of-Care Ultrasonography for Cardiac Tamponade Among Emergency Physicians.

STUDY OBJECTIVE: Cardiac tamponade is an impending calamitous disorder that emergency physicians need to consider and diagnose rapidly. A pericardial effusion with right atrial systolic collapse (earliest sign) or right ventricular diastolic collapse (most specific sign) and a plethoric inferior vena cava are indicators of cardiac tamponade physiology and may be identified with point-of-care ultrasonography (POCUS). The goal of this study is to assess the agreement among emergency physicians with varying levels of sonographic training and expertise in interpreting echocardiographic signs of cardiac tamponade in adult patients.  Methods: Emergency physicians at different levels of training as sonographers were surveyed at didactic conferences at three major academic medical centers in northern New Jersey. Two cardiologists were also included in the study for comparison. Survey respondents were shown 15, 20-second video clips of patients who had presented to the emergency department (ED) with or without significant pericardial effusions and were asked to rate whether tamponade physiology was present or not. Data were collected anonymously on Google Forms (Google LLC, Mountain View, CA) and included self-reported levels of POCUS expertise and level of training. Data were analyzed using Fleiss' kappa (k). All patients had an echocardiogram performed by the department of cardiology within 24 hours of the POCUS, and the results are presented in the paper.  Results: There were 97 participant raters, including attendings, fellows, and resident physicians specializing in adult emergency medicine and two cardiologists. There was a fair degree of inter-rater agreement among all participants in interpreting whether tamponade physiology was present or not. This low level of agreement persisted across self-reported training levels and self-reported POCUS expertise, even at the expert level in both emergency medicine and cardiology specialties. CONCLUSION: According to the results of our study, there appears to be a low level of agreement in the interpretation of cardiac tamponade in adult patients. The lack of agreement persisted across specialties, self-reported training levels, and self-reported ultrasonographic expertise. This low level of agreement seen among both specialists indicates that emergency physicians are not limited in their ability to determine cardiac tamponade on POCUS. This highlights the technical nature of POCUS clips and strengthens the importance of physical exam findings when diagnosing cardiac tamponade in emergency department patients. Further research utilizing POCUS for the diagnosis of tamponade is warranted.

Surgeon Quality and Patient Survival After Resection for Non-Small-Cell Lung Cancer.

PURPOSE: The quality and outcomes of curative-intent lung cancer surgery vary in populations. Surgeons are key drivers of surgical quality. We examined the association between surgeon-level intermediate outcomes differences, patient survival differences, and potential mitigation by processes of care. PATIENTS AND METHODS: Using a baseline population-based surgical resection cohort, we derived surgeon-level cut points for rates of positive margins, nonexamination of lymph nodes, nonexamination of mediastinal lymph nodes, and wedge resections. Applying the baseline cut points to a subsequent cohort from the same population-based data set, we assign surgeons into three performance categories in reference to each metric: 1 (<25th percentile), 2 (25th-75th percentile), and 3 (>75th percentile). The sum of performance scores created three surgeon quality tiers: 1 (4-6, low), 2 (7-9, intermediate), and 3 (10-12, high). We used chi-squared, Wilcoxon-Mann-Whitney, and Kruskal-Wallis tests to compare patient characteristics between the baseline and subsequent cohorts and across surgeon tiers. We applied Cox proportional hazards models to examine the association between patient survival and surgeon performance tier, sequentially adjusting for clinical stage, patient characteristics, and four specific processes. RESULTS: From 2009 to 2021, 39 surgeons performed 4,082 resections across the baseline and subsequent cohorts. Among 31 subsequent cohort surgeons, five were tier 1, five were tier 2, and 21 were tier 3. Tier 1 and 2 surgeons had significantly worse outcomes than tier 3 surgeons (hazard ratio [HR], 1.37; 95% CI, 1.10 to 1.72 and 1.19; 95% CI, 1.00 to 1.43, respectively). Adjustment for specific processes mitigated the surgeon-tiered survival differences, with adjusted HRs of 1.02 (95% CI, 0.8 to 1.3) and 0.93 (95% CI, 0.7 to 1.25), respectively. CONCLUSION: Readily accessible intermediate outcomes metrics can be used to stratify surgeon performance for targeted process improvement, potentially reducing patient survival disparities.

The epidemiology of HIV population viral load in twelve sub-Saharan African countries.

BACKGROUND: We examined the epidemiology and transmission potential of HIV population viral load (VL) in 12 sub-Saharan African countries. METHODS: We analyzed data from Population-based HIV Impact Assessments (PHIAs), large national household-based surveys conducted between 2015 and 2019 in Cameroon, Cote d'Ivoire, Eswatini, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe. Blood-based biomarkers included HIV serology, recency of HIV infection, and VL. We estimated the number of people living with HIV (PLHIV) with suppressed viral load (<1,000 HIV-1 RNA copies/mL) and with unsuppressed viral load (viremic), the prevalence of unsuppressed HIV (population viremia), sex-specific HIV transmission ratios (number female incident HIV-1 infections/number unsuppressed male PLHIV per 100 persons-years [PY] and vice versa) and examined correlations between a variety of VL metrics and incident HIV. Country sample sizes ranged from 10,016 (Eswatini) to 30,637 (Rwanda); estimates were weighted and restricted to participants 15 years and older. RESULTS: The proportion of female PLHIV with viral suppression was higher than that among males in all countries, however, the number of unsuppressed females outnumbered that of unsuppressed males in all countries due to higher overall female HIV prevalence, with ratios ranging from 1.08 to 2.10 (median: 1.43). The spatial distribution of HIV seroprevalence, viremia prevalence, and number of unsuppressed adults often differed substantially within the same countries. The 1% and 5% of PLHIV with the highest VL on average accounted for 34% and 66%, respectively, of countries' total VL. HIV transmission ratios varied widely across countries and were higher for male-to-female (range: 2.3-28.3/100 PY) than for female-to-male transmission (range: 1.5-10.6/100 PY). In all countries mean log10 VL among unsuppressed males was higher than that among females. Correlations between VL measures and incident HIV varied, were weaker for VL metrics among females compared to males and were strongest for the number of unsuppressed PLHIV per 100 HIV-negative adults (R2 = 0.92). CONCLUSIONS: Despite higher proportions of viral suppression, female unsuppressed PLHIV outnumbered males in all countries examined. Unsuppressed male PLHIV have consistently higher VL and a higher risk of transmitting HIV than females. Just 5% of PLHIV account for almost two-thirds of countries' total VL. Population-level VL metrics help monitor the epidemic and highlight key programmatic gaps in these African countries.

Aerobic Exercise Alters the Melanoma Microenvironment and Modulates ERK5 S496 Phosphorylation.

Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a phenotypic shift in the tumor-associated macrophage population and increased the expression of MHC class II transcripts. We further demonstrated that ERK5 S496A knock-in mice, which are phosphorylation deficient at the S496 residue, "mimicked" the exercise effect when unexercised, yet when exercised, these mice displayed a reversal in the effect of exercise on tumor growth and macrophage polarization compared with wild-type mice. Taken together, our results reveal tumor-specific differences in the immune response to exercise and show that ERK5 signaling via the S496 residue plays a crucial role in exercise-induced tumor microenvironment changes. See related Spotlight by Betof Warner, p. 1158.

Evaluation of Latex Immunoturbidimetric Assay Thresholds and HIT in Cardiothoracic Surgery.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a common differential diagnosis in cardiothoracic surgery. The latex immunoturbidimetric assay (LIA) is an enhanced immunoassay that has recently been introduced for the detection of total HIT immunoglobulin and retains a higher specificity of 95% compared to the enzyme-linked immunosorbent assay. OBJECTIVES: To investigate if a semiquantitative relationship exists between increasing LIA levels beyond the current positivity threshold and its correlation to positive serotonin release assay results in cardiothoracic surgery. METHODS: This was a multicenter, observational cohort of cardiothoracic surgery patients initiated on anticoagulation with heparin-based products. To conduct sensitivity and specificity analysis of LIA values, HIT positive was defined as a LIA value ≥1 unit/mL and HIT negative was defined as a LIA level <1 unit/mL. A receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive performance of the LIA. RESULTS: At manufactures' cutoffs of ≥1.0 unit/mL, LIA sensitivity and specificity was 93.8% and 22%, respectively, yielding a false positive rate of 78%. At a higher cutoff of 4.5 units/mL, LIA sensitivity and specificity was 75% and 71%, respectively, yielding a false positive rate of 29% and an area under the ROC curve of 0.75 (P = .01; 95% confidence interval: 0.621-0.889). Bivalirudin was initiated in 84.6% of false positive LIA results. CONCLUSION: This study suggests that the diagnostic accuracy of the LIA can be optimized by increasing the LIA positivity threshold. Proposing a higher LIA cutoff, may mitigate unwarranted anticoagulation and bleeding outcomes.

The state of the pediatric HIV epidemic in Lesotho.

OBJECTIVE: Lesotho does not have reliable data on HIV prevalence in children, relying on estimates generated from program data. The 2016 Lesotho Population-based HIV Impact Assessment (LePHIA) aimed to determine HIV prevalence among children 0-14 years to assess the effectiveness of the prevention of mother-to-child transmission (PMTCT) program and guide future policy. METHODS: A nationally representative sample of children under 15 years underwent household-based, two-stage HIV testing from November 2016-May 2017. Children <18 months with a reactive screening test were tested for HIV infection using total nucleic acid (TNA) PCR. Parents (61.1%) or legal guardians (38.9%) provided information on children's clinical history. Children aged 10-14 years also answered a questionnaire on knowledge and behaviors. RESULTS: HIV prevalence was 2.1% [95% confidence interval (CI): 1.5-2.6]. Prevalence in 10-14 year olds (3.2%; 95% CI: 2.1, 4.2) was significantly greater compared to 0-4 year olds (1.0%; 95% CI: 0.5, 1.6). HIV prevalence in girls and boys was 2.6% (95% CI: 1.8-3.3) and 1.5% (95% CI: 1.0-2.1), respectively. Based on reported status and/or the presence of detectable antiretrovirals, 81.1% (95% CI: 71.7-90.4) of HIV-positive children were aware of their status, 98.2% (95% CI: 90.7-100.0) of those aware were on antiretroviral therapy (ART) and 73.9% (95% CI: 62.1-85.8) of those on ART were virally suppressed. CONCLUSIONS: Despite the roll-out of Option B+ in Lesotho in 2013, pediatric HIV prevalence remains high. Further research is required to understand the greater prevalence among girls, barriers to PMTCT, and how to better achieve viral suppression in children with HIV.

Point of Care CD4 Testing in National Household Surveys - Results and Quality Indicators from Eleven Population-Based HIV Impact Assessment (PHIA) Surveys.

Population-based HIV Impact Assessments (PHIAs) are national household (HH) surveys that provide HIV diagnosis and CD4 testing with an immediate return of results. Accurate CD4 results improve HIV-positive participants' clinical care and inform the effectiveness of HIV programs. Here, we present CD4 results from the PHIA surveys that were conducted in 11 countries in sub-Saharan Africa between 2015 and 2018. All of the HIV-positive participants and 2 to 5% of the HIV-negative participants were offered Pima CD4 (Abbott, IL, USA) point-of-care (POC) tests. The quality of the CD4 test was ensured by conducting instrument verification, comprehensive training, quality control, a review of testing errors and an analysis of unweighted CD4 data by HIV status, age, gender, and antiretroviral (ARV) treatment status. Overall, CD4 testing was completed for 23,085 (99.5%) of the 23,209 HIV-positive and 7,329 (2.7%) of the 270,741 negative participants in 11 surveys. The instrument error rate was 11.3% (range, 4.4% to 15.7%). The median CD4 values among HIV-positive and HIV-negative participants (aged 15+) were 468 cells/mm3 (interquartile range [IQR], 307 to 654) and 811 cells/mm3 (IQR, 647 to 1,013), respectively. Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm3) than those with undetectable ARVs (385.5 cells/mm3). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm3, and approximately half of them (1,225/2,528 = 48.5%) had detectable ARVs, whereas 51.5% (1,303/2,528) had no detectable ARVs (P < 0.0001). We successfully implemented high quality POC CD4 testing using Pima instruments. Our data come from nationally representative surveys in 11 countries and provide unique insights regarding the CD4 distribution among HIV-positive individuals as well as the baseline CD4 values among HIV-negative individuals. IMPORTANCE The manuscript describes CD4 levels among HIV-positive individuals and baseline CD4 levels among HIV-negative individuals from 11 sub-Saharan countries, thereby highlighting the importance of CD4 markers in the context of the HIV epidemic. Despite increased ARV access in each country, advanced HIV disease (CD4 < 200 cells/mm3) persists among approximately 11% of HIV-positive individuals. Therefore, it is important that our findings are shared with the scientific community to assist with similar implementations of point-of-care testing and to conduct a review of HIV programmatic gaps.

Factors associated with viral suppression among adults living with HIV on antiretroviral therapy in Nigeria: Analysis of a population-based survey, 2018.

OBJECTIVE: Viral load suppression (VLS) is critical in reducing morbidity and mortality associated with HIV as well as minimizing the likelihood of HIV transmission to uninfected persons. The objective of this study was to identify factors associated with VLS among people living with HIV (PLWH) on antiretroviral (ARV) therapy to inform HIV programme strategies in Nigeria. METHODS: Adult participants, aged 15-64 years, from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS), who self-reported to be a PLWH or had detectable ARVs, were analysed to examine factors associated with VLS defined as HIV RNA <1000 copies/mL. NAIIS measured HIV prevalence, viral load, ARV and hepatitis B in PLWH. Logistic regression models were used and reported weighted prevalence. RESULTS: Of 1322 participants, 949 (68.25%) were women and 1287 (96.82%) had detectable ARVs. The median age was 39.31 [interquartile range (IQR): 31.47-47.63] years. Prevalence of VLS was 80.88%. Compared with participants with detectable ARVs, those with undetectable ARVs in their blood specimens had lower odds of VLS [adjusted odds ratio (aOR) = 0.24, 95% confidence interval (CI): 0.08-0.64). Coinfection with hepatitis B and nonnucleoside reverse transcriptase inhibitor metabolites were also associated with lower odds of VLS. Older people (45-54 vs 15-24 years) had increased odds of VLS (aOR = 2.81, 95% CI: 1.14-6.90). CONCLUSION: Young people and those with undetectable ARVs had lower odds of virological suppression. Targeted interventions focusing on young people and adherence to medication are needed to achieve the UNAIDS 95-95-95 goals for HIV epidemic control.

An electrophysiological substrate of COVID-19.

SARS-CoV-2 infection is associated with an increased risk of late cardiovascular (CV) outcomes. However, more data is needed to describe the electrophysiologic (EP) manifestation of post-acute CV sequelae of COVID-19. We compared two cohorts of adult patients with SARS-CoV-2 polymerase chain reaction (PCR) test and an electrocardiogram (ECG) performed between March 1, 2020, and September 13, 2020, in a retrospective double-cohort study, "Cardiovascular Risk Stratification in Covid-19" (CaVaR-Co19; NCT04555187). Patients with positive PCR comprised a COVID-19(+) cohort (n = 41; 61% women; 80% symptomatic), whereas patients with negative tests formed the COVID-19(-) cohort (n = 155; 56% women). In longitudinal analysis, comparing 3 ECGs recorded before, during, and on average 40 days after index COVID-19 episode, after adjustment for demographic and socioeconomic characteristics, baseline CV risk factors and comorbidities, use of prescription medications (including QT-prolonging drugs) before and during index COVID-19 episode, and the longitudinal changes in RR' intervals, heart rhythm, and ventricular conduction type, only in the COVID-19(+) cohort QTc increased by +30.2(95% confidence interval [CI] 0.1-60.3) ms and the spatial ventricular gradient (SVG) elevation increased by +13.5(95%CI 1.2-25.9)°. In contrast, much smaller, statistically nonsignificant changes were observed in the COVID-19(-) cohort. In conclusion, post-acute CV sequelae of SARS-CoV-2 infection manifested on ECG by QTc prolongation and rotation of the SVG vector upward.

Benzodiazepine, Z-drug, and sleep medication prescriptions in male and female people with opioid use disorder on buprenorphine and comorbid insomnia: an analysis of multistate insurance claims.

STUDY OBJECTIVES: In adult populations, women are more likely than men to be prescribed benzodiazepines. However, such disparities have not been investigated in people with opioid use disorder (OUD) and insomnia receiving buprenorphine, a population with particularly high sedative/hypnotic receipt. This retrospective cohort study used administrative claims data from Merative MarketScan Commercial and MultiState Medicaid Databases (2006-2016) to investigate sex differences in the receipt of insomnia medication prescriptions among patients in OUD treatment with buprenorphine. METHODS: We included people aged 12-64 years with diagnoses of insomnia and OUD-initiating buprenorphine during the study timeframe. The predictor variable was sex (female versus male). The primary outcome was receipt of insomnia medication prescription within 60 days of buprenorphine start, encompassing benzodiazepines, Z-drugs, or non-sedative/hypnotic insomnia medications (e.g. hydroxyzine, trazodone, and mirtazapine). Associations between sex and benzodiazepine, Z-drug, and other insomnia medication prescription receipt were estimated using Poisson regression models. RESULTS: Our sample included 9510 individuals (female n = 4637; male n = 4873) initiating buprenorphine for OUD who also had insomnia, of whom 6569 (69.1%) received benzodiazepines, 3891 (40.9%) Z-drugs, and 8441 (88.8%) non-sedative/hypnotic medications. Poisson regression models, adjusting for sex differences in psychiatric comorbidities, found female sex to be associated with a slightly increased likelihood of prescription receipt: benzodiazepines (risk ratio [RR], RR = 1.17 [1.11-1.23]), Z-drugs (RR = 1.26 [1.18-1.34]), and non-sedative/hypnotic insomnia medication (RR = 1.07, [1.02-1.12]). CONCLUSIONS: Sleep medications are commonly being prescribed to individuals with insomnia in OUD treatment with buprenorphine, with sex-based disparities indicating a higher prescribing impact among female than male OUD treatment patients.

Prevalence of HIV drug resistance in Nigeria: results from a cross-sectional, population-based survey of Nigerian adults with unsuppressed viral load.

BACKGROUND: HIV drug resistance (HIVDR) surveillance is an important tool to monitor threats to progress towards epidemic control. The characterization of HIVDR in Nigeria at the national level is needed to inform both clinical decisions and population-level HIV policy strategies. This study uses data obtained from the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) to describe the prevalence and distribution of HIVDR in Nigeria. METHODS: NAIIS was a cross-sectional, population-based survey of households throughout Nigeria in 2018. NAIIS was designed to provide estimates of HIV prevalence and related health indicators from a nationally representative sample. The study population included participants aged 15-64 years who tested positive for HIV, had a viral load at least 1000 copies/ml, and had available HIV drug resistance genotypes. HIV isolates were genotyped to detect drug resistance mutations. Individual characteristics of study participants associated with HIVDR were identified using a weighted multivariable logistic regression model. RESULTS: Of 1355 respondents with available HIV genotypes, 293 (19%) had evidence of drug-resistant mutations (DRMs) that conferred resistance to at least one antiretroviral drug. The majority of DRMs observed conferred resistance to NNRTIs (17.6%) and NRTIs (11.2%). HIVDR was associated with being ART-experienced, longer duration on ART, and lower CD4+ count but not sociodemographic characteristics. CONCLUSION: The population level DRM prevalence in Nigeria was consistent with what would be expected in a mature HIV treatment landscape. The continued roll out of dolutegravir-anchored regimens should mitigate the impact of NNRTI resistance on population viral load suppression and progress towards epidemic control.

HIV Incidence, Recent HIV Infection, and Associated Factors, Kenya, 2007-2018.

Nationally representative surveys provide an opportunity to assess trends in recent human immunodeficiency virus (HIV) infection based on assays for recent HIV infection. We assessed HIV incidence in Kenya in 2018 and trends in recent HIV infection among adolescents and adults in Kenya using nationally representative household surveys conducted in 2007, 2012, and 2018. To assess trends, we defined a recent HIV infection testing algorithm (RITA) that classified as recently infected (<12 months) those HIV-positive participants that were recent on the HIV-1 limiting antigen (LAg)-avidity assay without evidence of antiretroviral use. We assessed factors associated with recent and long-term (≥12 months) HIV infection versus no infection using a multinomial logit model while accounting for complex survey design. Of 1,523 HIV-positive participants in 2018, 11 were classified as recent. Annual HIV incidence was 0.14% in 2018 [95% confidence interval (CI) 0.057-0.23], representing 35,900 (95% CI 16,300-55,600) new infections per year in Kenya among persons aged 15-64 years. The percentage of HIV infections that were determined to be recent was similar in 2007 and 2012 but fell significantly from 2012 to 2018 [adjusted odds ratio (aOR) = 0.31, p < .001]. Compared to no HIV infection, being aged 25-34 versus 35-64 years (aOR = 4.2, 95% CI 1.4-13), having more lifetime sex partners (aOR = 5.2, 95% CI 1.6-17 for 2-3 partners and aOR = 8.6, 95% CI 2.8-26 for ≥4 partners vs. 0-1 partners), and never having tested for HIV (aOR = 4.1, 95% CI 1.5-11) were independently associated with recent HIV infection. Although HIV remains a public health priority in Kenya, HIV incidence estimates and trends in recent HIV infection support a significant decrease in new HIV infections from 2012 to 2018, a period of rapid expansion in HIV diagnosis, prevention, and treatment.