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Despite effective control of plasma viremia with the use of combination antiretroviral therapies (cART), minor cognitive and motor disorders (MCMD) persist as a significant clinical problem in HIV-infected patients. Non-human primate models are therefore required to study mechanisms of disease progression in the central nervous system (CNS). We isolated a strain of simian immunodeficiency virus (SIV), SIVsm804E, which induces neuroAIDS in a high proportion of rhesus macaques and identified enhanced antagonism of the host innate factor BST-2 as an important factor in the macrophage tropism and initial neuro-invasion of this isolate. In the present study, we further developed this model by deriving a molecular clone SIVsm804E-CL757 (CL757). This clone induced neurological disorders in high frequencies but without rapid disease progression and thus is more reflective of the tempo of neuroAIDS in HIV-infection. NeuroAIDS was also induced in macaques co-inoculated with CL757 and the parental AIDS-inducing, but non-neurovirulent SIVsmE543-3 (E543-3). Molecular analysis of macaques infected with CL757 revealed compartmentalization of virus populations between the CNS and the periphery. CL757 exclusively targeted the CNS whereas E543-3 was restricted to the periphery consistent with a role for viral determinants in the mechanisms of neuroinvasion. CL757 would be a useful model to investigate disease progression in the CNS and as a model to study virus reservoirs in the CNS.

Introduction Unhealthy alcohol use significantly contributes to viral non‐suppression among persons with HIV (PWH). It is unknown whether brief behavioural interventions to reduce alcohol use can improve viral suppression among PWH with unhealthy alcohol use in sub‐Saharan Africa (SSA). Methods As part of the SEARCH study (NCT04810650), we conducted an individually randomized trial in Kenya and Uganda of a brief, skills‐based alcohol intervention among PWH with self‐reported unhealthy alcohol use (Alcohol Use Disorders Identification Test–Consumption [AUDIT‐C], prior 3 months, ≥3/female; ≥4/male) and at risk of viral non‐suppression, defined as either recent HIV viral non‐suppression (≥400 copies/ml), missed visits, out of care or new diagnosis. The intervention included baseline and 3‐month in‐person counselling sessions with interim booster phone calls every 3 weeks. The primary outcome was HIV viral suppression (<400 copies/ml) at 24 weeks, and the secondary outcome was unhealthy alcohol use, defined by AUDIT‐C or phosphatidylethanol (PEth), an alcohol biomarker, ≥50 ng/ml at 24 weeks. Results Between April and September 2021, 401 persons (198 intervention, 203 control) were enrolled from HIV clinics in Uganda (58%) and Kenya (27%) and alcohol‐serving venues in Kenya (15%). At baseline, 60% were virally suppressed. Viral suppression did not differ between arms at 24 weeks: suppression was 83% in intervention and 82% in control arms (RR: 1.01, 95% CI: 0.93–1.1). Among PWH with baseline viral non‐suppression, 24‐week suppression was 73% in intervention and 64% in control arms (RR 1.15, 95% CI: 0.93–1.43). Unhealthy alcohol use declined from 98% at baseline to 73% in intervention and 84% in control arms at 24 weeks (RR: 0.86, 95% CI: 0.79–0.94). Effects on unhealthy alcohol use were stronger among women (RR 0.70, 95% CI: 0.56–0.88) than men (RR 0.93, 95% CI: 0.85–1.01) and among participants with a baseline PEth⩽200 ng/ml (RR 0.68, 95% CI: 0.53–0.87) versus >200 ng/ml (RR 0.97, 95% CI: 0.92–1.02). Conclusions In a randomized trial of 401 PWH with unhealthy alcohol use and risk for viral non‐suppression, a brief alcohol intervention reduced unhealthy alcohol use but did not affect viral suppression at 24 weeks. Brief alcohol interventions have the potential to improve the health of PWH in SSA by reducing alcohol use, a significant driver of HIV‐associated co‐morbidities.

IntroductionUnhealthy alcohol use is associated with a range of adverse outcomes among people with HIV (PWH). Testing the efficacy and promoting the availability of effective interventions to address unhealthy alcohol use among PWH is thus a priority. Alcohol use outcomes in intervention studies are often measured by self-report alone, which can lead to spurious results due to information biases (eg, social desirability). Measuring alcohol outcomes objectively through biomarkers, such as phosphatidylethanol (PEth), in addition to self-report has potential to improve the validity of intervention studies. This protocol outlines the methods for a systematic review and individual participant data meta-analysis that will estimate the efficacy of interventions to reduce alcohol use as measured by a combined categorical self-report/PEth variable among PWH and compare these estimates to those generated when alcohol is measured by self-report or PEth alone.Methods and analysisWe will include randomised controlled trials that: (A) tested an alcohol intervention (behavioural and/or pharmacological), (B) enrolled participants 15 years or older with HIV; (C) included both PEth and self-report measurements, (D) completed data collection by 31 August 2023. We will contact principal investigators of eligible studies to inquire about their willingness to contribute data. The primary outcome variable will be a combined self-report/PEth alcohol categorical variable. Secondary outcomes will include PEth alone, self-report alone and HIV viral suppression. We will use a two-step meta-analysis and random effects modelling to estimate pooled treatment effects; I2 will be calculated to evaluate heterogeneity. Secondary and sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots will be used to explore publication bias.Ethics and disseminationThe study will be conducted with deidentified data from completed randomised controlled trials and will be considered exempt from additional ethical approval. Results will be disseminated through peer-reviewed publications and international scientific meetings.PROSPERO registration numberCRD42022373640.

Disseminated sporotrichosis may present with inflammatory arthritis and cutaneous ulcerations that mimic noninfectious skin conditions such as pyoderma gangreonsum (PG). Sporotrichosis must therefore be ruled out before administering immunosuppressive agents for PG. Furthermore, dimorphic fungi such as sporotrichosis may grow as yeast in bacterial cultures, even before fungal cultures become positive. We present a case of disseminated cutaneous and osteoarticular sporotrichosis mimicking PG and describe the differential diagnosis and the diagnostic and treatment approach to this condition.

Background Undernutrition among people living with HIV (PLWHIV) can be ameliorated if nutrition specific and sensitive interventions are integrated into their HIV care and treatment centers (CTC). Integrated care is lacking despite expansion of antiretroviral therapy (ART) coverage, representing a substantial missed opportunity. This research aims to examine nutritional status and associated risk factors among HIV-positive adults prior to ART initiation in Tanzania in order to characterize existing gaps and inform early integration of nutrition care into CTC. Methods We analyzed data from 3993 pre-ART adults living with HIV enrolled in CTCs within the Trial of Vitamin (TOV3) and progression of HIV/AIDS study in Dar es salaam, Tanzania. The primary outcome for this analysis was undernutrition, measured as body mass index (BMI) below 18.5 kg/m 2 . We conducted descriptive analyses of baseline characteristics and utilized multiple logistic regression to determine independent factors associated with pre-ART undernutrition. Results Undernutrition was prevalent in about 27.7% of pre-ART adults, with a significantly higher magnitude among males compared to females (30% vs. 26.6%, p  < 0.025). Severe undernutrition (BMI < 16.0 kg/m 2 ) was prevalent in one in four persons, with a trend toward higher magnitudes among females (26.2% vs. 21.1% p  = 0.123). Undernutrition was also more prevalent among younger adults ( p  < 0.001), those with lower wealth quintiles ( p  = 0.003), and those with advanced HIV clinical stage ( p  < 0.001). Pre-ART adults presented with poor feeding practices, hallmarked by low dietary diversity scores and infrequent consumption of proteins, vegetables, and fruits. After adjusting for confounders and important co-variates, pre-ART undernutrition was associated with younger age, low wealth indices, advanced clinical stage, and low dietary diversity. Conclusions One in every four pre-ART PLWHIV presented with undernutrition in Dar es salaam, Tanzania. Risk factors for undernourishment included younger age, lower household income, advanced HIV clinical stage, and lower dietary diversity score. Knowledge of the prevalence and prevailing risk factors for undernutrition among pre-ART PLWHIV should guide targeted, early integration of nutrition interventions into routine HIV care and treatment in high-prevalence, low-income settings such as Tanzania.

Alcohol use was associated with elevated COVID-19 risk in the general population. People with HIV (PWH) have high prevalences of alcohol use. To evaluate the effect of alcohol use on COVID-19 risks among PWH, we estimated the risk of COVID-19 diagnosis and COVID-19-related hospitalization among PWH in routine care at 8 HIV primary care centers that contributed data to the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort according to their alcohol use just prior to the COVID-19 pandemic. The CNICS data repository includes demographic characteristics, clinical diagnoses, and laboratory test results from electronic medical records and other sources. Alcohol use, substance use, and mental health symptoms were self-reported on tablet-based standardized surveys. Alcohol use was categorized according to standard, sex-specific Alcohol Use Disorder Identification Test-Consumption instrument cut-offs. We followed 5,496 PWH (79% male, 48% Black race, median age = 53 years) from March 1, 2020 to December 31, 2020. Relative to PWH with no baseline alcohol use, the adjusted hazard ratio (aHR) of COVID-19 diagnosis was 1.09 (95% confidence interval [CI]: 0.78, 1.51) for lower-risk drinking and 1.19 (95%CI: 0.81, 1.73) for unhealthy drinking. The aHR of COVID-19-related hospitalization was 0.82 (95%CI: 0.33, 1.99) for lower-risk drinking and 1.25 (95%CI: 0.50, 3.09) for unhealthy drinking. Results were not modified by recent cocaine or non-prescribed opioid use, depressive symptoms, or diagnoses of alcohol use disorder. The study suggested a slightly increased, but not statistically significant risk of COVID-19 diagnosis and hospitalization associated with unhealthy alcohol use.

To better understand the impact of Uganda’s initial COVID-19 lockdown on alcohol use, we conducted a cross-sectional survey (August 2020-September 2021) among persons with HIV (PWH) with unhealthy alcohol use (but not receiving an alcohol intervention), enrolled in a trial of incentives to reduce alcohol use and improve isoniazid preventive therapy. We examined associations between bar-based drinking and decreased alcohol use, and decreased alcohol use and health outcomes (antiretroviral therapy [ART] access, ART adherence, missed clinic visits, psychological stress and intimate partner violence), during lockdown. Of 178 adults surveyed whose data was analyzed, (67% male, median age: 40), 82% reported bar-based drinking at trial enrollment; 76% reported decreased alcohol use during lockdown. In a multivariate analysis, bar-based drinking was not associated with greater decreases in alcohol use during lockdown compared to non-bar-based drinking (OR = 0.81, 95% CI: 0.31–2.11), adjusting for age and sex. There was a significant association between decreased alcohol use and increased stress during lockdown (adjusted β = 2.09, 95% CI: 1.07–3.11, P < 0.010), but not other health outcomes.

Abstract Tuberculosis (TB) remains the leading cause of death among people with human immunodeficiency virus (PWH). The diagnosis of latent TB infection (LTBI) and treatment with TB preventative therapy (TPT) can reduce morbidity and mortality in this population. Historically, isoniazid has been recommended for TPT in PWH due to the absence of drug-drug interactions with most antiretroviral therapy (ART). However, newer rifamycin-based regimens are safer, shorter in duration, associated with improved adherence, and may be as or more effective than isoniazid TPT. Current guidelines have significant heterogeneity in their recommendations for TPT regimens and acceptability of drug interactions with modern ART. In this Infectious Diseases learning unit, we review common questions on diagnosis, treatment, and drug interactions related to the management of LTBI among PWH. The repertoire of data-driven medication regimens to treat latent tuberculosis infection (LTBI) among people with HIV (PWH) is rapidly evolving, leading to heterogeneity in published guidelines. We review the emerging data regarding LTBI management among PWH to support patient-centered care.

BackgroundMany individuals with HIV in the USA are unaware of their diagnosis, and therefore cannot be engaged in treatment services, have worse clinical outcomes and are more likely to transmit HIV to others. Mobile van testing may increase HIV testing and diagnosis. Our objective was to characterise risk factors for HIV seroconversion among individuals using mobile van testing.MethodsA case cohort study (n=543) was conducted within an HIV surveillance dataset of mobile van testing users with at least two HIV tests between September 2004 and August 2009 in Baltimore, Maryland. A subcohort (n=423) was randomly selected; all additional cases were added from the parent cohort. Cases (n=122 total, two from random subcohort) had documented seroconversion at the follow-up visit. A unique aspect of the analysis was use of Department of Corrections data to document incarceration between the times of initial and subsequent testing. Multivariate Cox proportional hazards models were used to compare HIV transmission risk factors between individuals who seroconverted and those who did not.ResultsOne hundred and twenty-two HIV seroconversions occurred among 8756 individuals (1.4%), a rate higher than that in Baltimore City Health Department’s STD Clinic clients (1%). Increased HIV seroconversion risk was associated with men who have sex with men (MSM) (HR 32.76, 95% CI 5.62 to 191.12), sex with an HIV positive partner (HR 70.2, 95% CI 9.58 to 514.89), and intravenous drug use (IDU) (HR 5.65, 95% CI 2.41 to 13.23).ConclusionsHIV testing is a crucial first step in the HIV care continuum and an important HIV prevention tool. This study confirmed the need to reach high-risk populations (MSM, sex with HIV-positive individuals, individuals with IDU) and to increase comprehensive prevention services so that high-risk individuals stay HIV uninfected. HIV testing in mobile vans may be an effective outreach strategy for identifying infection in certain populations at high risk for HIV.

Conservation successes of the past several decades provide natural settings to study post-bottleneck evolutionary processes in species undergoing recovery. Here, we study the impact of demographic change on genetic diversity in parallel natural experiments of historical decline and subsequent recovery in two sympatric pinniped species in the Northwest Atlantic, the gray seal (Halichoerus grypus atlantica) and harbor seal (Phoca vitulina concolor). We compare genetic diversity at the mitochondrial control region today to diversity in archaeological specimens, which represent the populations prior to the regional bounties of the late 1800s to mid-1900s that drastically reduced population sizes and led to local extirpations. We further assess genetic diversity throughout recovery, using biological collections from ongoing long-term studies of both species. Overall, the genetic data are consistent with the historical presence of large, genetically diverse populations of pinnipeds prior to human exploitation, and suggest that gray seals were more dramatically impacted by historical bottlenecks than harbor seals in the Northwest Atlantic. Current mitochondrial diversity in both species is relatively high, and we observe little change over the past several decades during a period of roughly parallel rapid population increases. However, there remain large differences in haplotype composition between pinniped populations of pre-exploitation and today, a lasting genetic signature of historical exploitation that is likely to persist into the future.