Comparison of SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction and BinaxNOW Rapid Antigen Tests at a Community Site During an Omicron Surge : A Cross-Sectional Study.

BACKGROUND: SARS-CoV-2 rapid antigen tests are an important public health tool. OBJECTIVE: To evaluate field performance of the BinaxNOW rapid antigen test (Abbott) compared with reverse transcriptase polymerase chain reaction (RT-PCR) for detecting infection with the Omicron variant of SARS-CoV-2. DESIGN: Cross-sectional surveillance study. SETTING: Free, walk-up, outdoor, urban community testing and vaccine site led by Unidos en Salud, serving a predominantly Latinx community highly impacted by COVID-19. PARTICIPANTS: Persons seeking COVID-19 testing in January 2022. MEASUREMENTS: Simultaneous BinaxNOW and RT-PCR from nasal, cheek, and throat swabs, including cycle threshold (Ct) measures; a lower Ct value is a surrogate for higher amounts of virus. RESULTS: Among 731 persons tested with nasal swabs, there were 296 (40.5%) positive results on RT-PCR; 98.9% were the Omicron variant. BinaxNOW detected 95.2% (95% CI, 91% to 98%) of persons who tested positive on RT-PCR with a Ct value below 30, 82.1% (CI, 77% to 87%) of those who tested positive on RT-PCR with a Ct value below 35, and 65.2% (CI, 60% to 71%) of all who were positive on RT-PCR. Among 75 persons with simultaneous nasal and cheek swabs, BinaxNOW using a cheek swab failed to detect 91% (20 of 22) of specimens that were positive on BinaxNOW with a nasal swab. Among persons with simultaneous nasal and throat swabs who were positive on RT-PCR with a Ct value below 30, 42 of 49 (85.7%) were detected by nasal BinaxNOW, 23 of 49 (46.9%) by throat BinaxNOW, and 44 of 49 (89.8%) by either. LIMITATION: Participants were a cross-sectional sample from a community-based sentinel surveillance site, precluding study of viral or symptom dynamics. CONCLUSION: BinaxNOW detected persons with high SARS-CoV-2 levels during the Omicron surge, enabling rapid responses to positive test results. Cheek or throat swabs should not replace nasal swabs. As currently recommended, high-risk persons with an initial negative BinaxNOW result should have repeated testing. PRIMARY FUNDING SOURCE: University of California, San Francisco.

The epidemiology of chronic kidney disease (CKD) in rural East Africa: A population-based study.

BACKGROUND: Chronic kidney disease (CKD) may be common among individuals living in sub-Saharan Africa due to the confluence of CKD risk factors and genetic predisposition. METHODS: We ascertained the prevalence of CKD and its risk factors among a sample of 3,686 participants of a population-based HIV trial in rural Uganda and Kenya. Prevalent CKD was defined as a serum creatinine-based estimated glomerular filtration rate <60 mL/min/1.73m2 or proteinuria (urine dipstick ≥1+). We used inverse-weighting to estimate the population prevalence of CKD, and multivariable log-link Poisson models to assess the associations of potential risk factors with CKD. RESULTS: The estimated CKD prevalence was 6.8% (95% CI 5.7-8.1%) overall and varied by region, being 12.5% (10.1-15.4%) in eastern Uganda, 3.9% (2.2-6.8%) in southwestern Uganda and 3.7% (2.7-5.1%) in western Kenya. Risk factors associated with greater CKD prevalence included age ≥60 years (adjusted prevalence ratio [aPR] 3.5 [95% CI 1.9-6.5] compared with age 18-29 years), HIV infection (aPR 1.6 [1.1-2.2]), and residence in eastern Uganda (aPR 3.9 [2.6-5.9]). However, two-thirds of individuals with CKD did not have HIV, diabetes, or hypertension as risk factors. Furthermore, we noted many individuals who did not have proteinuria had dipstick positive leukocyturia or hematuria. CONCLUSION: The prevalence of CKD is appreciable in rural East Africa and there are considerable regional differences. Conventional risk factors appear to only explain a minority of cases, and leukocyturia and hematuria were common, highlighting the need for further research into understanding the nature of CKD in sub-Saharan Africa.

High rates of viral suppression in adults and children with high CD4+ counts using a streamlined ART delivery model in the SEARCH trial in rural Uganda and Kenya.

INTRODUCTION: The 2015 WHO recommendation of antiretroviral therapy (ART) for all HIV-positive persons calls for treatment initiation in millions of persons newly eligible with high CD4+ counts. Efficient and effective care models are urgently needed for this population. We evaluated clinical outcomes of asymptomatic HIV-positive adults and children starting ART with high CD4+ counts using a novel streamlined care model in rural Uganda and Kenya. METHODS: In the 16 intervention communities of the HIV test-and-treat Sustainable East Africa Research for Community Health Study (NCT01864603), all HIV-positive individuals irrespective of CD4 were offered ART (efavirenz [EFV]/tenofovir disoproxil fumarate + emtricitabine (FTC) or lamivudine (3TC). We studied adults (≥fifteen years) with CD4 ≥ 350/µL and children (two to fourteen years) with CD4 > 500/µL otherwise ineligible for ART by country guidelines. Clinics implemented a patient-centred streamlined care model designed to reduce patient-level barriers and maximize health system efficiency. It included (1) nurse-conducted visits with physician referral of complex cases, (2) multi-disease chronic care (including for hypertension/diabetes), (3) patient-centred, friendly staff, (4) viral load (VL) testing and counselling, (5) three-month return visits and ART refills, (6) appointment reminders, (7) tiered tracking for missed appointments, (8) flexible clinic hours (outside routine schedule) and (9) telephone access to clinicians. Primary outcomes were 48-week retention in care, viral suppression (% with measured week 48 VL ≤ 500 copies/mL) and adverse events. Results Overall, 972 HIV-positive adults with CD4+ ≥ 350/µL initiated ART with streamlined care. Patients were 66% female and had median age thirty-four years (IQR, 28-42), CD4+ 608/µL (IQR, 487-788/µL) and VL 6775 copies/mL (IQR, <500-37,003 c/mL). At week 48, retention was 92% (897/972; 2 died/40 moved/8 withdrew/4 transferred care/21/964 [2%] were lost to follow-up). Viral suppression occurred in 778/838 (93%) and 800/972 (82%) in intention-to-treat analysis. Grade III/IV clinical/laboratory adverse events were rare: 95 occurred in 74/972 patients (7.6%). Only 8/972 adults (0.8%) switched ART from EFV to lopinavir (LPV) (n = 2 for dizziness, n = 2 for gynaecomastia, n = 4 for other reasons). Among 83 children, week 48 retention was 89% (74/83), viral suppression was 92% (65/71) and grade III/IV adverse events occurred in 4/83 (4.8%). CONCLUSIONS: Using a streamlined care model, viral suppression, retention and ART safety were high among asymptomatic East African adults and children with high CD4+ counts initiating treatment. CLINICAL TRIAL NUMBER: NCT01864603.

Population levels and geographical distribution of HIV RNA in rural Ugandan and Kenyan communities, including serodiscordant couples: a cross-sectional analysis.

BACKGROUND: As sub-Saharan Africa transitions to a new era of universal antiretroviral therapy (ART), up-to-date assessments of population-level HIV RNA suppression are needed to inform interventions to optimise ART delivery. We sought to measure population viral load metrics to assess viral suppression and characterise demographic groups and geographical locations with high-level detectable viraemia in east Africa. METHODS: The Sustainable East Africa Research in Community Health (SEARCH) study is a cluster-randomised controlled trial of an HIV test-and-treat strategy in 32 rural communities in Uganda and Kenya, selected on the basis of rural setting, having an approximate population of 10 000 people, and being within the catchment area of a President's Emergency Plan for AIDS Relief-supported HIV clinic. During the baseline population assessment in the SEARCH study, we did baseline HIV testing and HIV RNA measurement. We analysed stable adult (aged ≥15 years) community residents. We defined viral suppression as a viral load of less than 500 copies per mL. To assess geographical sources of transmission risk, we established the proportion of all adults (both HIV positive and HIV negative) with a detectable viral load (local prevalence of viraemia). We defined transmission risk hotspots as geopolitical subunits within communities with an at least 5% local prevalence of viraemia. We also assessed serodiscordant couples, measuring the proportion of HIV-positive partners with detectable viraemia. The SEARCH study is registered with ClinicalTrials.gov, number NCT01864603. FINDINGS: Between April 2, 2013, and June 8, 2014, of 303 461 stable residents, we enumerated 274 040 (90·3%), of whom 132 030 (48·2%) were adults. Of these, 117 711 (89·2%) had their HIV status established, of whom 11 964 (10·2%) were HIV positive. Of these, we measured viral load in 8828 (73·8%) people. Viral suppression occurred in 3427 (81·6%) of 4202 HIV-positive adults on ART and 4490 (50·9%) of 8828 HIV-positive adults. Regional viral suppression among HIV-positive adults occurred in 881 (48·2%) of 1827 people in west Uganda, 516 (45·0%) of 1147 in east Uganda, and 3093 (52·8%) of 5854 in Kenya. Transmission risk hotspots occurred in three of 21 parishes in west Uganda and none in east Uganda and in 24 of 26 Kenya geopolitical subunits. In Uganda, 492 (2·9%) of 16 874 couples were serodiscordant: in 287 (58·3%) of these couples, the HIV-positive partner was viraemic (and in 69 [14·0%], viral load was >100 000 copies per mL). In Kenya, 859 (10·0%) of 8616 couples were serodiscordant: in 445 (53·0%) of these couples, the HIV-positive partner was viraemic (and in 129 [15%], viral load was >100 000 copies per mL). INTERPRETATION: Before the start of the SEARCH trial, 51% of east African HIV-positive adults had viral suppression, reflecting ART scale-up efforts to date. Geographical hotspots of potential HIV transmission risk and detectable viraemia among serodiscordant couples warrant intensified interventions. FUNDING: National Institute of Allergy and Infectious Diseases (National Institutes of Health) and the President's Emergency Plan for AIDS Relief.

Will the Nineties Be the Decade We Lost the Battle Against Drug-Resistant Microbes?

Antimicrobial resistance is reaching epidemic proportions. Bacteria have developed an impressive array of defenses to protect themselves against potent compounds. The widespread emergence of resistance has complicated the treatment of infections due to Staphylococcus, Streptococcus, Enterococcus, Neisseria, Haemophilus, gram-negative enteric bacilli, and Pseudomonas. Multidrug-resistant tuberculosis poses a grave public health problem, particularly among the homeless and those infected with HIV. HIV resistance to nucleoside analogs such as zidovudine is increasingly common and seriously threatens their clinical usefulness. It is apparent that simply producing new drugs is not a viable solution to the resistance crisis. Rational use of existing antimicrobial agents is vital, and combination regimens must be intelligently deployed. State-of-the-art molecular epidemiology will aid in the detection, analysis, and termination of resistance epidemics. Control of drug-resistant Mycobacterium tuberculosis will require appropriate initial treatment regimens, proper therapeutic modification using the latest susceptibility testing methods, and strong emphasis on measures ensuring compliance. HIV resistance is a challenging problem, and novel strategies will be necessary to combat it. Recognition that drug resistance among bacteria and viruses is a rapidly growing threat worldwide is an important first step toward finding effective long-term solutions.

Successful antiretroviral therapy delivery and retention in care among asymptomatic individuals with high CD4+ T-cell counts above 350 cells/µl in rural Uganda.

BACKGROUND: HIV antiretroviral therapy (ART) is being rapidly scaled up in sub-Saharan Africa, including recently patients with CD4 T-cell counts above 350 cells/µl. However, concerns persist about adherence and virologic suppression among these asymptomatic, high CD4 cell count individuals. OBJECTIVE: To determine the virologic efficacy and safety of ART among asymptomatic HIV-positive Ugandan adults with high CD4 cell counts above 350 cells/µl via a streamlined model of care. DESIGN: Prospective nonrandomized clinical study (EARLI Study: clinicaltrials.gov NCT#01479634). SETTING: Prototypic rural Ugandan HIV clinic. PATIENTS/PARTICIPANTS: Asymptomatic, ART-naive adults (aged >18 years, N = 197) with CD4 at least 350 cells/µl, without pregnancy or WHO stage 3/4 illness. INTERVENTIONS: ART included tenofovir/emtricitabine/efavirenz, with ritonavir/lopinavir substitution for efavirenz available. Streamlined ART model included nurse-driven visits with physician back-up, basic safety laboratory monitoring with HIV viral load, clinician telephone contact, and defaulter tracking. No incentives were provided. OUTCOMES: Undetectable viral load (≤400 copies/ml) at 24 and 48 weeks [intention to treat (ITT); missing = detectable), self-reported ART adherence, retention in care, and laboratory/clinical ART toxicities. RESULTS: Of the 197 patients with CD4 above 350 cells/µl, median CD4 cell count was 569 cells/µl (interquartile range 451-716). Undetectable viral load was achieved in 189 of 197 (95.9%, ITT) and 189 of 195 (96.9%, ITT) of participants at weeks 24 and 48, respectively. Self-reported adherence was 98% and 192 of 197 (97%) of the patients were retained at week 48. Laboratory adverse events and hospitalizations were rare. CONCLUSIONS: We demonstrate high virologic suppression, retention, and safety among asymptomatic individuals with CD4 above 350 cells/µl in a prototypic Ugandan clinic. Our results challenge current concerns that individuals with high CD4 cell count lack motivation for ART, and may not achieve sustained virologic suppression.

Economic issues and antibiotic resistance in the community.

BACKGROUND: Inappropriate antibiotic use is generally considered to be the primary cause of antibiotic resistance in the community. Multiple economic factors, at the level of physicians, patients, healthcare organizations, and pharmaceutical companies, foster poor antibiotic use. OBJECTIVE: To describe the influence of economic factors on the use and development of antibiotics and to evaluate the extent to which the cost of resistance is important in the economic evaluation of antibiotic products. DATA SOURCES: Literature identified through MEDLINE (1966-May 2001), bibliographies from relevant articles, government reports, and proceedings from conferences about antibiotic resistance. DATA SYNTHESIS: Economic factors at all levels of the healthcare system contribute to the inappropriate use of antibiotics in the community setting. Relatively little economic research has been published on antibiotic resistance, and very few cost-effectiveness analyses of antibiotic treatment alternatives have explicitly included the cost of resistance. CONCLUSIONS: A better understanding of economic factors that influence the prescribing, marketing, and development of antibiotics could lead to more successful efforts at curtailing the growth of antibiotic resistance in the community setting.

Effect of long-term highly active antiretroviral therapy in restoring HIV-induced abnormal B-lymphocyte function.

Although highly active antiretroviral therapy (HAART) has been reported to restore defects in cell-mediated immunity to a significant degree, little is known of its effects in restoring HIV-induced abnormal antibody-mediated immunity. We conducted a cross-sectional study of 1) 29 HIV-infected patients on chronic HAART whose HIV viral load was undetectable and whose absolute CD4+ T-lymphocyte count had been consistently sustained by > or =150 cells/microL over their pre-HAART nadir value for >1 year; and 2) 29 untreated HIV-infected patients with current CD4 counts matching the treated patients' prior nadir CD4 counts. Serum was tested for total IgG and by protein electrophoresis with immunofixation for paraproteins. Although serum IgG levels were significantly lower in patients who had received long-term virologically effective HAART than in CD4 count-matched untreated patients (1488 +/- 475 mg/dL vs. 1999 +/- 775 mg/dL, p =.004), serum IgG was still abnormally elevated in 45% of the untreated group despite a mean 28 months of HAART-induced HIV suppression and CD4 count restoration. Paraprotein spikes were confirmed by immunofixation in 7% of patients in each group. This study provides the longest reported observation to date of the effect of HAART on HIV-induced abnormal antibody-mediated immunity. Larger and longer-term studies of HAART effect on B-cell reconstitution are needed.