Pivoting from in-person to phone survey assessment of alcohol and substance use: effects on representativeness in a United States prospective cohort of women living with and without HIV.

Background: Many clinical and population-based research studies pivoted from in-person assessments to phone-based surveys due to the COVID-19 pandemic. The impact of these transitions on survey response remains understudied, especially for people living with HIV. Given that there are gender-specific trends in alcohol and substance use, it is particularly important to capture these data for women.Objective: Identify factors associated with responding to an alcohol and substance use phone survey administered during the COVID-19 pandemic in the Women's Interagency HIV Study, a multicenter US prospective cohort of women living with and without HIV.Methods: We used multivariable logistic regression to assess for associations of pre-pandemic (April-September 2019) sociodemographic factors, HIV status, housing status, depressive symptoms, alcohol use, and substance use with response to an early-pandemic (August-September 2020) phone survey.Results: Of 1,847 women who attended an in-person visit in 2019, 78% responded to a phone survey during the pandemic. The odds of responding were lower for women of Hispanic ethnicity (aOR 0.47 95% CI 0.33-0.66, ref=Black/African American) and those who reported substance use (aOR 0.63 95% CI 0.41-0.98). By contrast, the odds were higher for White women (aOR 1.64 95% CI 1.02-2.70, ref=Black/African American) and those with stable housing (aOR 1.74 95% CI 1.24-2.43).Conclusions: Pivoting from an in-person to phone-administered alcohol and substance use survey may lead to underrepresentation of key subpopulations of women who are often neglected in substance use and HIV research. As remote survey methods become more common, investigators need to ensure that the study population is representative of the target population.

Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State.

Importance: Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events. Objective: To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19. Design, Setting, and Participants: Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020. Exposures: Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither. Main Outcomes and Measures: Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation). Results: Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings. Conclusions and Relevance: Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.

Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia.

Human immunodeficiency virus (HIV) drug resistance is a major threat to the sustained impact of antiretroviral therapy (ART). We studied the epidemiology of drug resistance in the country of Georgia. The study included all adult patients who experienced virologic failure on first line ART and received HIV drug resistance testing between 2005 and 2016. The Stanford HIV Sequence Database was used for interpretation of the resistance data. Patient-level data were extracted from the national AIDS health information system. Of the 447 patients included, 85.5% harbored the subtype A6 virus, 8.0% - subtype B, 2.9% - subtype G, and other subtypes were <1%. The most frequent first-line regimens were Tenofovir/Emtricitabine/Efavirenz (28.4%), Zidovudine/Lamivudine/Efavirenz (28.4%), and Abacavir/Lamivudine/Efavirenz (15.9%). A total of 85.0% of the patients with treatment failure developed at least one drug resistance mutation affecting their susceptibility to ART. The most frequent nucleoside reverse transcriptase inhibitor mutations were M184V (65.3%), K65R (19.7%) and L74V (17.0%). At least three thymidine analogue mutations were detected in 6.3% of the patients. From non-nucleoside reverse transcriptase inhibitor mutations, G190S was shown to be the most prevalent (49.4%), followed by K101E (27.10%) and K103N (24.4%). G190S and K101E were more common in subtype A as compared with non-A viruses (G190S: 54.9% vs 11.3%, P < 0.0001; K101E: 29.8% vs 11.3%, P = 0.005). On the other hand, K103N was more frequent in non-A subtypes (43.4%) compared with subtype A (22.2%), P = 0.0008. A majority of persons failing on ART had HIV drug resistance. Drug resistance patterns may vary by subtype. K65R mutation remains below 20%, but given the high use of Tenofovir in the country, continuing surveillance of drug resistance is needed.

Implementation of antiretroviral therapy (ART) in former Soviet Union countries.

Against the current global trends, in the former Soviet Union (FSU) countries HIV prevalence is on the rise. Visa-free movement across borders has facilitated migrant-associated HIV transmission within this region. Despite efforts from the governments to curtail the growing epidemic, there is still a serious need for the development of strategies that focus on high-risk behaviors and practices responsible for the continued transmission of HIV in this region. While governments of FSU countries have taken commendable steps in recent years to address hurdles at each step of the HIV care continuum, to ensure 100% antiretroviral treatment (ART) accessibility to people living with HIV (PLHIV), testing for HIV needs to be enforced widely in FSU countries. Stigma against people who inject drugs (PWID), men who have sex with men (MSM), migrants, and PLHIV need to be addressed. Finally, to avoid breaks in ART supply, FSU countries need to gain independence in funding HIV care so that the provision of ART to PLHIV is made available without interruption.

Reproductive Aging and Hepatic Fibrosis Progression in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Women.

BACKGROUND: Severity of hepatic fibrosis is greater in postmenopausal than in premenopausal women, perhaps owing to protective effects of estrogens. However, prior studies of estrogen and liver fibrosis lack serial fibrosis measures, adjustment for age, or longitudinal observations in coinfected populations. METHODS: In a longitudinal cohort of women coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), we assessed fibrosis progression across reproductive age, using validated serum fibrosis markers, aminotransferase platelet ratio index (APRI) and fibrosis 4 (FIB-4). Fibrosis rate was evaluated within each woman as she transitioned from pre- to postmenopause, defined by a biomarker of ovarian function. RESULTS: The median follow-up (n = 405) was 9.1 years (interquartile range, 5.0-15.2 years), with a median menopausal age of 49 years (47-52 years). When fully controlled for chronologic aging, the fibrosis progression rate was accelerated during perimenopause, as shown using FIB-4 (0.12 units per year faster than during premenopause; 95% confidence interval [CI], .02-.21; P = .01) and APRI (0.05 units per year faster; -.002 to .09; P = .06). Accelerated fibrosis was also observed during postmenopause compared with premenopause, for FIB-4 (0.14 units per year faster; 95% CI, -.01 to .29; P = .07) and APRI (0.07 units per year faster; -.003 to .15; P = .06). Accelerated fibrosis in perimenopause persisted after adjustment for Hispanic ethnicity, antiretroviral use, and alcohol (0.10 FIB-4 units per year faster than during premenopause; 95% CI, .008-.20; P = .03). CONCLUSIONS: In HIV/HCV-coinfected women, hepatic fibrosis accelerates with reproductive aging. Accelerated fibrosis begins in perimenopause, highlighting a previously unrecognized group of women at increased risk for advanced fibrosis and associated complications. Longitudinal analyses of fibrosis rates across reproductive age should be conducted in non-HCV-related liver diseases, given potential implications in a broader spectrum of women.

The HIV epidemic in Eastern Europe and Central Asia.

Eastern Europe and Central Asia represent one of the few regions globally where there is a continued increase in the incidence of HIV infection. For example, in Eastern Europe the rate of diagnosed cases of HIV infection per 100 000 population has increased from 11.7 in 2004 to 22.5 in 2011. Initially propelled by injection drug use, heterosexual transmission has now become a major driver of new infections in the region. Nonetheless substance use remains an important factor, with its control limited by challenges in scaling up harm reduction efforts. While most countries have implemented opioid substitution therapy programs, their scale remains very limited. Similarly, coverage of needles syringe programs across the region is variable. Complicating the control of HIV has been the emergence of non-injection drugs and inadequate access to antiretroviral therapy. In addition, structural barriers and stigma toward HIV infected people may contribute to the high proportion of late presentations for HIV care. Finally in the wake of the HIV epidemic, high rates of hepatitis C infection and tuberculosis have been noted.

HIV stigma and other barriers to COVID-19 vaccine uptake among Georgian people living with HIV/AIDS: A mixed-methods study.

We conducted a study in Georgia to examine behavioral insights and barriers to COVID-19 vaccine uptake among people living with HIV (PLWH). Between December 2021-July 2022, we collected quantitative data to evaluate participants' demographics, COVID-19 knowledge, attitude, perception, and HIV stigma as potential covariates for being vaccinated against COVID-19. We conducted a multivariate analysis to define the factors independently associated with COVID-19 vaccination among PLWH. We collected qualitative data to explore individual experiences of their positive or negative choices, main barriers, HIV stigma, and preferences for receiving vaccination. Of the total 85 participants of the study, 52.9% were vaccinated; 61.2% had concerns with the disclosure of HIV status at the vaccination site. Those who believed they would have a severe form of COVID-19 were more likely to be vaccinated (OR = 23.8; 95% CI: 5.1-111.7). The association stayed significant after adjusting for sex, age, education level, living area, health care providers' unfriendly attitudes, and their fear of disclosing HIV status at vaccination places. Based on the qualitative study, status disclosure was a significant barrier to receiving care; therefore, PLWH prefer to receive COVID-19 vaccination integrated in HIV services. Conclusions: In this study, around half of the participants were not vaccinated against COVID-19. The main reasons for not being vaccinated included stigma, misleading health beliefs, and low awareness about COVID-19. An integrated service delivery model may improve vaccination uptake among PLWH in Georgia.

Developing an adherence support intervention for patients on antiretroviral therapy in the context of the recent IDU-driven HIV/AIDS epidemic in Estonia.

There is limited data on and experience with interventions for antiretroviral therapy (ART) adherence support for patients on ART in Eastern Europe. We sought to identify a feasible adherence support intervention for delivery amongst HIV-positive adults receiving care in Estonia, where the HIV/AIDS epidemic has been mainly concentrated among injection drug users (IDUs). Our application of intervention mapping (IM) strategies used existing literature, formative research and multidisciplinary team input to produce a brief clinic-based intervention entitled the Situated Optimal Adherence Intervention Estonia (sOAI Estonia) which uses both Next-Step Counseling (NSC) and Information-Motivation-Behavioral Skills (IMB) Model approach to facilitate integration of ART into the context and demands of daily life. We present the intervention development process, the resulting sOAI Estonia approach, and describe a randomized controlled trial (RCT) which is under way to evaluate the intervention (results due in spring 2013).

A single-nucleotide polymorphism in CYP2B6 leads to >3-fold increases in efavirenz concentrations in plasma and hair among HIV-infected women.

BACKGROUND: Efavirenz exhibits marked interindividual variability in plasma levels and toxicities. Prior pharmacogenetic studies usually measure exposure via single plasma levels, examine limited numbers of polymorphisms, and rarely model multiple contributors. We analyzed numerous genetic and nongenetic factors impacting short-term and long-term exposure in a large heterogeneous population of human immunodeficiency virus (HIV)-infected women. METHODS: We performed 24-hour intensive pharmacokinetic studies in 111 women receiving efavirenz under actual-use conditions and calculated the area-under-the-concentration-time curve (AUC) to assess short-term exposure; the efavirenz concentration in hair was measured to estimate long-term exposure. A total of 182 single-nucleotide polymorphisms (SNPs) and 45 haplotypes in 9 genes were analyzed in relationship to exposure by use of multivariate models that included a number of nongenetic factors. RESULTS: Efavirenz AUCs increased 1.26-fold per doubling of the alanine aminotransferase level and 1.23-fold with orange and/or orange juice consumption. Individuals with the CYP2B6 516TT genotype displayed 3.5-fold increases in AUCs and 3.2-fold increases in hair concentrations, compared with individuals with the TG/GG genotype. Another SNP in CYP2B6 (983TT) and a p-glycoprotein haplotype affected AUCs without substantially altering long-term exposure. CONCLUSIONS: This comprehensive pharmacogenomics study showed that individuals with the CYP2B6 516TT genotype displayed >3-fold increases in both short-term and long-term efavirenz exposure, signifying durable effects. Pharmacogenetic testing combined with monitoring of hair levels may improve efavirenz outcomes and reduce toxicities.

Are persons living with diagnosed HIV capable of mounting a strong inflammatory response to the new coronavirus?

BACKGROUND: The impact of COVID-19 on persons living with diagnosed HIV (PLWDH) remains incompletely understood. It's unclear whether an impaired immune system offers protection against mounting cytokine storm. METHODS: Retrospective matched cohort study of COVID-19 hospitalized individuals in New York State (NYS). Medical records were abstracted and analyzed for 853 PLWDH hospitalized with COVID-19 in NYS and 1621 HIV-negative controls. Preexisting comorbidities and inflammatory markers measured within 24 h of hospital admission were abstracted. RESULTS: PLWDH were significantly less likely to have elevated inflammatory markers compared to matched controls. Elevated WBC occurred in 23.3% of PLWDH vs 30.1% of controls (p = .0002), elevated CRP in 37.4% of PLWDH vs 43.2% of controls (p = .03), elevated ferritin in 73.4% of PLWDH vs 78.9% of controls (p = .004). There was an inverse but not statistically significant relationship between the frequency of elevated inflammatory markers and HIV disease stage, with greatest percent of PLWDH with elevated WBC, LDH, CRP, and ferritin among PLWDH with HIV disease stage 1. CONCLUSION: PLWDH had lower inflammatory marker elevation during COVID-19 infection compared to matched controls. PLWDH with low CD4 were less likely to mount a cytokine storm in the setting of impaired immune function.

Characterization of HIV-1 subtypes and drug resistance mutations among individuals infected with HIV in Georgia.

In order to describe HIV-1 subtypes and drug resistance mutations in Georgia, blood samples from 153 patients infected with HIV-1 collected from 2006 to 2008 were genotyped. Of these, 126 samples were from newly diagnosed, antiretroviral (ARV)-naïve patients and 27 from ARV-treated patients. Partial pol region sequences were used to identify drug resistance mutations and to conduct phylogenetic analysis for subtype determination. The results indicated that 138 (90.2%) patients harbored subtype A viruses, 11 (7.2%) carried subtype B virus, two subtype G (1.3%), one (0.6%) subtype F and one (0.6%) 03_AB recombinant. All subtype A strains clustered with the Former Soviet Union A (A FSU) subtype. Among patients with no prior exposure to ARVs, mutations associated with resistance were detected in five patients: three (2.4%) patients had reverse transcriptase (RT) inhibitor mutations and two other patients had the protease (PI) inhibitor associated mutation M46I. PI mutation V77I was found in 42 of subtype A isolates. Of 27 ARV-treated patients, 22 (81.5%) harbored at least one nucleoside reverse transcriptase inhibitors (NRTI), a non-NRTI (NNRTI) and/or a PI mutation. The most common NRTI resistance mutation was M184V/I (74.1%). Frequency of thymidine analog mutations was relatively low (25.9%). With regard to NNRTI mutations, G190S/A was the most frequent mutation, which might be a preferred mutations for subtype A. Georgia's HIV epidemic continues to be dominated by Subtype A FSU. The prevalence of transmitted drug resistance is low, but has the potential to increase with increasing use of ARVs.

Antiretroviral therapy (ART) adherence and correlates to nonadherence among people on ART in Estonia.

There are little data on antiretroviral therapy (ART) adherence among patients in Eastern Europe, despite the high incidence of HIV infection and the growing number of HIV-infected individuals who are being prescribed ART. The aim of this study was to measure rates of adherence to ART and factors associated with nonadherence among patients receiving care at an outpatient HIV clinic in Estonia. The study was based on cross-sectional data from a convenience sample of 144 patients receiving outpatient HIV care. Data were obtained via interviewer-administered surveys and data abstraction from clinical records. Adherence was measured from a 3-day patient self-report. Among 144 participants (mean age 33.8 years), two-thirds (63%) had been infected with HIV through intravenous drug use. Most (74%) were co-infected with hepatitis C (HCV). Perfect adherence over the last 3 days was commonly reported (88% [95% CI 81-92%]) with nonperfect adherence associated with greater concerns about the potential adverse consequences of taking ART (adjusted odds ratio [AOR] 4.8, 95% CI 1.2-34.0) and average (versus good/very good) self-reported health status (AOR 4.7, 95% CI 1.2-31.4). Self-reported ART adherence in this sample of Estonian HIV-positive patients in clinical care was similar to rates observed in Western Europe and other developed countries. Results suggest that adherence education and support may be most helpful if they specifically target the development of positive beliefs, reduction of negative expectancies towards ART.

Associated factors for recommending HBV vaccination to children among Georgian health care workers.

BACKGROUND: Most cases of hepatitis B virus (HBV) infection and subsequent liver diseases can be prevented with universal newborn HBV vaccination. The attitudes of health care workers about HBV vaccination and their willingness to recommend vaccine have been shown to impact HBV vaccination coverage and the prevention of vertical transmission of HBV. The purpose of this study was to ascertain the factors associated with health care worker recommendations regarding newborn HBV vaccination. METHODS: A cross-sectional study of prevalence and awareness of hepatitis B and hepatitis B vaccine was conducted among randomly selected physicians and nurses employed in seven hospitals in Georgia in 2006 and 2007. Self-administered questionnaires included a module on recommendations for HBV, HCV and HIV. RESULTS: Of the 1328 participants included in this analysis, 36% reported recommending against hepatitis B vaccination for children, including 33% of paediatricians. Among the 70.6% who provided a reason for not recommending HBV vaccine, the most common concern was an adverse vaccine event. Unvaccinated physicians and nurses were more likely to recommend against HBV vaccine (40.4% vs 11.4%, PR 3.54; 95% CI: 2.38, 5.29). Additionally, health care worker age was inversely correlated with recommendations for HBV vaccine with older workers less likely to recommend it. CONCLUSION: Vaccinating health care workers against HBV may provide a dual benefit by boosting occupational safety as well as strengthening universal coverage programs for newborns.

Factors associated with SARS-CoV-2-related hospital outcomes among and between persons living with and without diagnosed HIV infection in New York State.

BACKGROUND: Persons living with diagnosed HIV (PLWDH) are at increased risk for severe illness due to COVID-19. The degree to which this due to HIV infection, comorbidities, or other factors remains unclear. METHODS: We conducted a retrospective matched cohort study of individuals hospitalized with COVID-19 in New York State between March and June 2020, during the first wave of the pandemic, to compare outcomes among 853 PLWDH and 1,621 persons without diagnosed HIV (controls). We reviewed medical records to compare sociodemographic and clinical characteristics at admission, comorbidities, and clinical outcomes between PLWDH and controls. HIV-related characteristics were evaluated among PLWDH. RESULTS: PLWDH were significantly more likely to have cardiovascular (matched prevalence-ratio [mPR], 1.22 [95% CI, 1.07-1.40]), chronic liver (mPR, 6.71 [95% CI, 4.75-9.48]), chronic lung (mPR, 1.76 [95% CI, 1.40-2.21]), and renal diseases (mPR, 1.77 [95% CI, 1.50-2.09]). PLWDH were less likely to have elevated inflammatory markers upon hospitalization. Relative to controls, PLWDH were 15% less likely to require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) and 15% less likely to require admission to the intensive care unit. No significant differences were found in in-hospital mortality. PLWDH on tenofovir-containing regimens were significantly less likely to require mechanical ventilation or ECMO (risk-ratio [RR], 0.73 [95% CI, 0.55-0.96]) and to die (RR, 0.74 [95% CI, 0.57-0.96]) than PLWDH on non-tenofovir-containing regimens. CONCLUSIONS: While hospitalized PLWDH and controls had similar likelihood of in-hospital death, chronic disease profiles and degree of inflammation upon hospitalization differed. This may signal different mechanisms leading to severe COVID-19.

Evaluation of the Abbott ARCHITECT HIV Ag/Ab combo assay for determining recent HIV-1 infection.

BACKGROUND: Given the challenges and costs associated with implementing HIV-1 incidence assay testing, there is great interest in evaluating the use of commercial HIV diagnostic tests for determining recent HIV infection. A diagnostic test with the capability of providing reliable data for the determination of recent HIV infection without substantial modifications to the test protocol would have a significant impact on HIV surveillance. The Abbott ARCHITECT HIV Ag/Ab Combo Assay is an antigen/antibody immunoassay, which meets the criteria as the first screening test in the recommended HIV laboratory diagnostic algorithm for the United States. METHODS: In this study, we evaluated the performance characteristics of the ARCHITECT HIV Ag/Ab Combo signal-to-cutoff ratio (S/Co) for determining recent infection, including estimation of the mean duration of recent infection (MDRI) and false recent rate (FRR), and selection of recency cutoffs. RESULTS: The MDRI estimates for the S/Co recency cutoff of 400 is within the 4 to 12 months range recommended for HIV incidence assays, and the FRR rate for this cutoff was 1.5%. Additionally, ARCHITECT Combo S/Co values were compared relative to diagnostic test results from two prior prospective HIV-1 diagnostic studies in order to validate the use of the S/Co for both diagnostic and recency determination. CONCLUSION: Dual-use of the ARCHITECT Combo assay data for diagnostic and incidence purposes would reduce the need for separate HIV incidence testing and allow for monitoring of recent infection for incidence estimation and other public health applications.

Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm.

The development of a rapid and efficient system to identify human immunodeficiency virus type 1 (HIV-1)-infected individuals with broad and potent HIV-1-specific neutralizing antibody responses is an important step toward the discovery of critical neutralization targets for rational AIDS vaccine design. In this study, samples from HIV-1-infected volunteers from diverse epidemiological regions were screened for neutralization responses using pseudovirus panels composed of clades A, B, C, and D and circulating recombinant forms (CRFs). Initially, 463 serum and plasma samples from Australia, Rwanda, Uganda, the United Kingdom, and Zambia were screened to explore neutralization patterns and selection ranking algorithms. Samples were identified that neutralized representative isolates from at least four clade/CRF groups with titers above prespecified thresholds and ranked based on a weighted average of their log-transformed neutralization titers. Linear regression methods selected a five-pseudovirus subset, representing clades A, B, and C and one CRF01_AE, that could identify top-ranking samples with 50% inhibitory concentration (IC(50)) neutralization titers of >or=100 to multiple isolates within at least four clade groups. This reduced panel was then used to screen 1,234 new samples from the Ivory Coast, Kenya, South Africa, Thailand, and the United States, and 1% were identified as elite neutralizers. Elite activity is defined as the ability to neutralize, on average, more than one pseudovirus at an IC(50) titer of 300 within a clade group and across at least four clade groups. These elite neutralizers provide promising starting material for the isolation of broadly neutralizing monoclonal antibodies to assist in HIV-1 vaccine design.

Transmission of HIV and HCV within Former Soviet Union Countries.

Background: Following the collapse of the Union of Soviet Socialist Republic (USSR) in 1991, trans-border mobility increased within the former Soviet Union (FSU) countries. In addition, drug-trafficking and injection drug use began to rise, leading to the propagation and transmission of blood-borne infections within and across the FSU countries. To examine the transmission of blood-borne infections within this region, we analyzed the phylogenetic relationship of publically available sequences of two blood-borne viruses, hepatitis C virus (HCV) and human immunodeficiency virus (HIV), from FSU countries. Methods: We analysed 614 and 295 NS5B sequences from HCV genotypes 1b and 3a, respectively, from 9 FSU countries. From 13 FSU countries, we analysed 347 HIV gag and 1282 HIV env sequences. To examine transmission networks and the origins of infection, respectively, phylogenetic and Bayesian analyses were performed. Results: Our analysis shows intermixing of HCV and HIV sequences, suggesting transmission of these viruses both within and across FSU countries. We show involvement of three major populations in transmission: injection drug user, heterosexual, and trans-border migrants. Conclusion: This study highlights the need to focus harm reduction efforts toward controlling transmission of blood-borne infections among the abovementioned high-risk populations in the FSU countries.

The positive affect, promoting Positive Engagement, and Adherence for Life (APPEAL) feasibility trial: Design and rationale.

OBJECTIVE: To describe development of the Positive Affect, Promoting Positive Engagement, and Adherence for Life (APPEAL) program. METHOD: APPEAL is intended to increase HIV medication adherence through promotion of positive affect, and was developed through an iterative process involving 6 focus groups (N = 34) that elicited feedback on intervention content, followed by an individually administered prepilot of the entire intervention (N = 7). RESULTS: Participants provided feedback on important potential moderator variables, including depression, on mode of intervention administration, and on anticipated barriers and benefits to participation. Insights gained were used to finalize study procedures in preparation for a feasibility trial. For the feasibility trial, a total of 80 participants who, in the past 6 months have had at least one plasma HIV RNA >200 copies/mL, will be randomized to receive APPEAL or standard of care (N = 40 per group). Intervention group participants will receive 3 monthly, individually administered sessions, and all participants will have their medication adherence monitored and complete structured interviews at baseline and at 3 and 6 months. CONCLUSION: The APPEAL program is innovative in that it focuses on promoting self-regulation of positive emotions, an understudied approach to promoting chronic disease self-management behaviors such as HIV medication adherence. Findings from the feasibility trial will gauge suitability of the APPEAL intervention and evaluation methods for subsequent testing in a confirmatory trial and will examine changes in positive affect, the primary mechanism of change targeted in the intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Treating COVID-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind Randomized Controlled Trial in Hospitalized Patients.

BACKGROUND: Effective therapies to combat coronavirus 2019 (COVID-19) are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19. METHODS: We conducted a multicenter, double-blind randomized clinical trial of HCQ among patients hospitalized with laboratory-confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for 5 days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite end point (death, intensive care unit admission, mechanical ventilation, extracorporeal membrane oxygenation, and/or vasopressor use) at day 14. RESULTS: A total of 128 patients were included in the intention-to-treat analysis. Baseline demographic, clinical, and laboratory characteristics were similar between the HCQ (n = 67) and placebo (n = 61) arms. At day 14, 11 (16.4%) subjects assigned to HCQ and 6 (9.8%) subjects assigned to placebo met the severe disease progression end point, but this did not achieve statistical significance (P = .350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend toward an increased length of stay. CONCLUSIONS: In hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed.

Intersectional Stigma and Multi-Level Barriers to HIV Testing Among Foreign-Born Black Men From the Caribbean.

Testing is the entry point into the HIV care continuum that includes linkage to and retention in prevention services, and adherence to prevention strategies, including repeat HIV testing. Despite US policy approaches to expand HIV testing to diverse clinical care and community settings, disparities in HIV testing among Black populations persist. Foreign-born (FB) Black persons from the Caribbean have higher annual rates of HIV diagnosis and a higher percentage of late-stage HIV diagnosis, compared with US-born Black persons; and most HIV infections among FB Blacks are among men. In this article, we provide an overview of HIV testing barriers among FB Black men who engage in HIV risk-taking behaviors (e.g., condomless sex with male and/or female partners of unknown HIV serostatus). Barriers to HIV testing for both FB and US-born Black men, include HIV stigma (anticipated, perceived, internalized), low perceived HIV risk, medical or government mistrust, and perceived low access to testing resources. We examine beliefs about masculinity and gender roles that may perpetuate heteronormative stereotypes associated with perceptions of low HIV risk and barriers to HIV testing. We also discuss the impact of recent immigration policies on accessing HIV testing and treatment services and how intersectional stigmas and structural forms of oppression, such as racism, prejudice against select immigrant groups, and homophobia that may further amplify barriers to HIV testing among FB Black men. Finally, we review comprehensive prevention approaches, and suggest innovative approaches, that may improve the uptake of HIV testing among FB Black men.