Cohort Of People Living With HIV Research Articles

71. Increasing Trends in Multimorbidity and Polypharmacy Over a 5-Year Period in People Living with HIV in the United States

BackgroundAdvances in antiretroviral therapies (ART) have resulted in people living with HIV (PLWH) living longer with higher risk for age-related comorbid conditions and polypharmacy. The aim of this study was to describe trends in comorbidity and comedication burden in PLWH over a 5-year time period. MethodsA retrospective analysis of commercial and Medicare Advantage enrollees from the Optum Research Database was conducted. Annual cohorts of PLWH were constructed for each calendar year from 2014-2018 and included adults (≥ 18 years) with ≥ 1 pharmacy claim for an ART or medical claim with an HIV/AIDS diagnosis code (index date=earliest claim date in each calendar year). Continuous health plan enrollment of 12 months prior to (baseline), and 30 days after index date was required for each annual cohort. Comorbidities were identified using ICD-9/10 diagnosis codes from medical claims during baseline period and comedications from pharmacy/medical claims in the 90-days prior to index using National Drug Codes. Charlson Comorbidity Index (CCI) was computed excluding HIV/AIDS. P-for-trend values accounting for clustering by patients across calendar years were assessed.ResultsOverall, 14,222 - 20,249 PLWH who were enrolled in commercial (80.7%-65.4%) or Medicare Advantage (19.3%-34.6%) plans were identified in 2014 - 2018 calendar years. Notable trends in demographics of PLWH were observed across years, including increases in mean age (48.9 to 52.4 years), proportion of females (17.2% to 20.3%) and Black race (25.9% to 29.0%), all p-trend< 0.001. Mean CCI scores increased across years (0.72 to 0.93), p-trend< 0.001. Multimorbidity (≥2 non-HIV conditions) and polypharmacy (≥ 5 non-ART medications) prevalence increased over 5 years (Figure 1). Hypertension, hyperlipidemia, neuropsychiatric conditions and Type 2 diabetes mellitus were the most prevalent comorbid conditions with statistically significant upward trends in prevalence across years (Figure 1). ConclusionMultimorbidity and polypharmacy are common in PLWH and have been increasing in prevalence over the past 5 years. Study findings highlight the importance of an individualized approach to care for a diverse PLWH population, in order to minimize drug-drug interactions and adverse events and thereby improve patient outcomes. Figure 1. Comorbidity and Comedication Trends by Index Year among People Living with HIV Disclosures Misti Paudel, PhD, Merck (Other Financial or Material Support, This study was funded by Merck & Co.) Girish Prajapati, M.B.B.S., MPH , Merck & Co., Inc. (Employee, Shareholder) Erin K. Buysman, MS, Merck & Co., Inc. (Other Financial or Material Support, I am an employee of Optum, which was contracted by Merck to complete the research described in this abstract) Jianbin Mao, PhD, Merck & Co. (Employee, Shareholder) Kimberly McNiff, MPH, Merck (Other Financial or Material Support, Merck funded the research project) Princy N. Kumar, MD, Amgen (Consultant)Eli Lilly (Grant/Research Support)Gilead (Consultant, Grant/Research Support, Shareholder)GSK (Consultant, Grant/Research Support, Shareholder)Merck (Consultant, Grant/Research Support, Shareholder, Honoraria)

Immunogenicity of an inactivated SARS-CoV-2 vaccine in people living with HIV-1: a non-randomized cohort study.

BackgroundInactivated COVID-19 vaccines are safe and effective in the general population with intact immunity. However, their safety and immunogenicity have not been demonstrated in people living with HIV (PLWH).Methods42 HIV-1 infected individuals who were stable on combination antiretroviral therapy (cART) and 28 healthy individuals were enrolled in this open-label two-arm non-randomized study at Hubei Provincial Center for Disease Control and Prevention, China. Two doses of an inactivated COVID-19 vaccine (BBIBP-CorV) were given on April 22, 2021 and May 25, 2021, respectively. The reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and surrogate neutralization assays. Cell-mediated immune responses and vaccine induced T cell activation were measured by flow cytometry.FindingsAll the HIV-1 infected participants had a CD4+ T cell count >200 cells/μL both at baseline (659·0 ± 221·9 cells/μL) and 4 weeks after vaccination (476·9 ± 150·8 cells/μL). No solicited adverse reaction was observed among all participants. Similar binding antibody, neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals. PLWH with low baseline CD4+/CD8+ T cell ratios (<0·6) generated lower antibody responses after vaccination than PLWH with medium (0·6∼1·0) or high (≥1·0) baseline CD4+/CD8+ T cell ratios (P<0·01). The CD3+, CD4+ and CD8+ T cell counts of PLWH decreased significantly after vaccination (P<0·0001), but it did not lead to any adverse clinical manifestation. Moreover, we found that the general HIV-1 viral load among the PLWH cohort decreased significantly after vaccination (P=0·0192). The alteration of HIV-1 viral load was not significantly associated with the vaccine induced CD4+ T cell activation (P>0·2).InterpretationOur data demonstrated that the inactivated SARS-CoV-2 vaccine was safe, immunogenic in PLWH who are stable on cART with suppressed viral load and CD4+ T cell count > 200 cells/μL. However, the persistence of the vaccine-induced immunities in PLWH need to be further investigated.

Brief Report: Yield of Repeat Tuberculin Skin Testing for People Living With HIV in Brazil.

In Brazil, annual tuberculin skin tests (TSTs) are recommended for people living with HIV (PLWH) with CD4 >350, with tuberculosis preventive therapy provided on test conversion. We aimed to determine the yield of repeat TSTs for PLWH. Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT) to prevent tuberculosis (TB). We analyzed data from newly registered PLWH with negative baseline TST results. We calculated the number of TST conversions after 1 and/or 2 years among patients eligible for follow-up TSTs, the proportion of converters initiating IPT, and incidence of TB/death. Among 1770 PLWH with a negative baseline TST, 679 (38%) were female and median age was 36 years (IQR 29-43). Eighty-six (5%) developed TB or died within 1 year. Among 1684 eligible for a follow-up 1-year TST, 582 (35%) were tested and 53 (9%) were positive. Forty-nine converters (92%) started IPT. Of 529 patients with a negative 1-year TST, 7 (1%) developed TB or died over the following year. Of 522 patients eligible for a 2-year TST, 158 (30%) were tested and 13 (8%) were positive. Ten converters (77%) started IPT. Of 1102 patients who did not receive a 1-year TST, 33 (3%) developed TB or died. Of the 1069 patients eligible for a 2-year TST, 259 (24%) were tested and 34 (13%) were positive. Thirty converters (88%) started IPT. In this cohort of PLWH in Brazil, TST conversion was high among those retested, but only 48% received a follow-up TST within 2 years.

Unbiased Metabolomics Links Fatty Acid Pathways to Psychiatric Symptoms in People Living with HIV

Psychiatric symptoms are prevalent in people living with HIV (PLWH), especially depression, anxiety, impulsivity, and substance use. Various biological mechanisms might play a role in the occurrence of psychiatric symptoms in this population. A hypothesis free, data-driven metabolomics approach can further our understanding of these mechanisms. In this study, we identified metabolic pathways associated with impulsivity, depression and substance use in 157 PLWH. First, Spearman’s rank correlations between metabolite feature intensities and psychiatric symptom levels were calculated, while controlling for age, gender and body mass index. Subsequently, a mummichog pathway analysis was performed. Finally, we analyzed which individual metabolites drove the observed effects. In our cohort of PLWH, fatty acid-related pathways were associated with both depressive as well as impulsive symptomatology. Substance use showed most extensive metabolic associations, and was positively associated with short chain fatty acids (SCFA’s), and negatively associated with glutamate levels. These findings suggest that PUFA metabolism might be associated with both internalising and externalising symptomatology in PLWH. Furthermore, glutamate and SCFA’s—microbiome derivatives with known neuroactive properties—might be involved in substance use in these patients. Future studies should explore potential causal mechanisms involved and whether these findings are HIV-specific.

IgG seroprevalence of COVID-19 among people living with HIV or at high risk of HIV in south-west Germany: A seroprevalence study.

ObjectivesSeroprevalence studies of SARS‐CoV‐2 have shown that there is a high number of undiagnosed missing cases. Seroprevalence of SARS‐CoV‐2 in people living with HIV (PLWH) is lacking. Therefore, we conducted a prospective cross‐sectional study to estimate the seroprevalence of SARS‐CoV‐2 among PLWH without known diagnosis of COVID‐19 in the south‐west of Germany.MethodsSerological testing for SARS‐CoV‐2 immunoglobulin G (IgG) antibodies based on two assays was performed in PLWH who visited the outpatient HIV centre of two hospitals from April to June 2020. Additionally, patients had to answer questionnaires about possible COVID‐19‐related symptoms and predefined risk factors. Moreover, we tested 50 non‐HIV‐infected patients receiving post‐ or pre‐exposure (PEP/PrEP) HIV prophylaxis.ResultsIn all, 594 (488 male, 106 female) PLWH (median age 51 years) and 50 PEP/PrEP‐users were included in the study. The estimated seroprevalence of the PLWH cohort was 1.85% (11/594), with 11 positive tested cases in the cohort. Among all patients, only five had COVID‐19‐related symptoms. One PCR‐positive patient did not show any antibody response in repeatedly carried out tests. None of the patients was hospitalized due to COVID‐19. Three PrEP users were tested positive. Three patients had been previously diagnosed with SARS‐COV‐2 infection before inclusion. The used questionnaire did not help to detect SARS‐CoV‐2 positive patients.ConclusionsDespite the limitation of being only a snapshot in time because of the ongoing pandemic, to our knowledge this is the largest study so far on seroprevalence of SARS‐CoV‐2 in PLWH in Germany. Our study suggests that the seroprevalence of SARS‐CoV‐2 in PLWH is comparable to those previously reported for parts of the general German population and that the questionnaire used here might not be the best tool to predict COVID‐19 diagnosis.

Factors associated with viremia in people living with HIV on antiretroviral therapy in Guatemala

IntroductionViral suppression prevents HIV transmission and disease progression, but socio-economic and clinical factors can hinder the goal of suppression. We evaluated factors associated with viral non suppression (VNS) and persistent viremia (PV) in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Guatemala.MethodsWe conducted a cross sectional analysis using data from an ongoing cohort of PLHIV attending the largest HIV clinic in Guatemala. Univariable and multivariable analyses were conducted between PLHIV with viral suppression and detectable viremia. VNS was defined as most recent HIV RNA ≥ 200 copies/ml and PV as two consecutive HIV RNA ≥ 200 copies/ml.ResultsOf 664 participants, 13.3% had VNS and 7.1% had PV. In univariable analysis disaggregated by gender, low income, poor education, perceived difficulty attending healthcare, and alcohol use were associated with VNS in men while low CD4 at diagnosis, multiple prior ART regimens and treatment interruptions were significant in both genders. Multiple prior ART regimens (adjusted Odds Ratio (aOR) 2.82, [95% confidence interval (CI) 1.59, 4.99], p < 0.01), treatment interruptions (aOR 4.51, [95% CI 2.13, 9.58], p < 0.01), excessive alcohol consumption (aOR 2.56, [95% CI 1.18, 5.54], p < 0.05) perceived difficulty attending healthcare (aOR 2.07, [ 95% CI 1.25, 3.42], p < 0.01) and low CD4 at diagnosis (aOR 2.34, 95% [CI 1.30, 4.20], p < 0.01) were independently associated with VNS on multivariable regression.ConclusionsWe conclude that socio-economic and clinical factors influence viral suppression in our cohort and vary between men and women. Gender specific approaches are necessary to achieve the 90% suppression goal.

Standardized Comparison of Cardiovascular Risk Factors Prevalence in Spanish Women and Men Living with HIV and in the General Population.

People living with HIV (PLWH) have an increased risk of cardiovascular (CV) disease, likely due to a higher prevalence of CV risk factors. We compared the age-standardized prevalence and management of CV risk factors in PLWH to that of the general population in Spain. Blood pressure, lipid, glucose, and anthropometric profiles were cross-sectionally compared along with the treatment of hypertension, dyslipidemia, and diabetes in a general population cohort and a PLWH cohort. Prevalence rates were standardized by the direct method by 10-year age groups in European standard populations and stratified by gender. We included 47,593 individuals aged 35 to 74 years, 28,360 from the general population cohort and 19,233 from the PLWH cohort. Compared to the general population, PLWH had a higher concentration of triglycerides (>35 mg/dL in women and >26 mg/dL in men) and a higher prevalence of smoking (>23% and >17%) and diabetes (>9.9% and >8.5%). The prevalence of treated diabetes, hypertension, and dyslipidemia were up to three-fold lower in both women and men living with HIV. There was a significant difference in PLWH compared to the general population in the lipid, glucose, and anthropometric profile. In addition, PLWH were less often treated for diagnosed diabetes, hypertension, and dyslipidemia.

Evaluation of SARS-CoV-2 Antibodies and the Impact of COVID-19 on the HIV Care Continuum, Economic Security, Risky Health Behaviors, and Mental Health Among HIV-Infected Individuals in Vietnam

Coronavirus disease 2019 (COVID-19) and associated social responses may uniquely affect people living with HIV (PLHIV). SARS-CoV-2 antibody testing and a cross-sectional survey on COVID-19’s socio-behavioral impacts were conducted among a large PLHIV cohort in Hanoi, Vietnam. We examined anonymous antibody test results for 1243 PLHIV (99.8%) from whom plasma was obtained and completed surveys were collected in June/July 2020, just after the end of the first COVID-19 outbreak and nationwide lockdown. Three participants (0.2%) tested positive for anti-SARS-CoV-2 IgG antibodies. HIV treatment was generally maintained without antiretroviral therapy interruption, but COVID-19 had substantial impacts on economic security and risky health behaviors among PLHIV, which may have amplified psychological stress. These findings highlight the need for continuous monitoring of COVID-19’s impacts on PLHIV and for efforts to mitigate these impacts.

EGFR-EPI changes among HIV patients who switch from F/TDF to F/TAF while maintaining the same third agent in the Spanish VACH cohort

Background: Evidence from clinical practice on the effects of switching from emtricitabine/tenofovir disoproxil fumarate (F/TDF) to emtricitabine/tenofovir alafenamide (F/TAF)-based triple-therapy (TT) regimens on renal parameters is limited. Objective: This retrospective analysis evaluated the effects on renal function of switching from F/TDF to F/TAF-based TT regimens with no change in third agent among people living with HIV (PLWH). Methods: Data were from a multicenter Spanish PLWH cohort. Patients with a baseline estimated glomerular filtration rate (eGFR-EPI) measurement, ≥1 follow-up measurement, ≥30 days treatment with F/TAF, and who switched from F/TDF to F/TAF with no change in third agent were included. Multivariate mixed linear models were used to evaluate change from baseline over time in eGFR-EPI. eGFR-EPI changes before and after switch were analyzed in a matched patient subgroup. Results: Overall, 340 patients were included. Mean (95% CI) eGFR-EPI in patients with baseline eGFR-EPI <90 ml/min/1.73m2 (n = 125) was 79.6 (78.0; 81.2) ml/min/1.73m2 at baseline and 81.3 (79.9; 82.7) ml/min/1.73m2 at 12 months after switch. In the patient-matched subgroup (n = 175), median annual eGFR-EPI declined −4.24 ml/min/1.73m2 while on F/TDF and increased +0.93 ml/min/1.73m2 after switch to F/TAF (P < 0.0001). In patients with baseline eGFR-EPI <90 ml/min/1.73m2, median annual eGFR-EPI increased +4.19 mL/min/1.73m2 after switch (P < 0.0001). Conclusion: Switching from F/TDF to F/TAF-based TT regimens while maintaining the same third agent numerically improved eGFR-EPI in PLWH with baseline eGFR-EPI <90 mL/min/1.73m2. eGFR-EPI improved significantly when comparing progression while on F/TDF vs progression after switch, confirming beneficial renal effects of switching to F/TAF in a clinical practice setting.

Assessing Cardiovascular Risk in People Living with HIV: Current Tools and Limitations.

To provide the current state of the development and application of cardiovascular disease (CVD) prediction tools in people living with HIV (PLWH). Several risk prediction models developed on the general population are available to predict CVD risk, the most notable being the US-based pooled cohort equations (PCE), the Framingham risk functions, and the Europe-based SCORE (Systematic COronary Risk Evaluation). In validation studies in cohorts of PLWH, these models generally underestimate CVD risk, especially in individuals who are younger, women, Black race, or predicted to be at low/intermediate risk. An HIV-specific CVD prediction model, the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, is available, but its performance is modest, especially in US-based cohorts. Enhancing CVD prediction with novel biomarkers of inflammation or coronary artery calcification is of interest but has not yet been evaluated in PLWH. Finally, studies on CVD risk prediction are lacking in diverse PLWH globally. While available risk models for CVD prediction in PLWH remain suboptimal, clinicians should remain vigilant of higher CVD risk in this population and should use any of these risk scores for risk stratification to guide preventive interventions. Focus on established traditional risk factors such as smoking remains critical in PLWH. Risk prediction functions tailored to PLWH in diverse settings will enhance clinicians' ability to deliver optimal preventive care.

Heavy Alcohol Use Among Women and Men Living With HIV in Uganda, Russia, and the United States

We examined whether gender is associated with heavy drinking in three cohorts of people living with HIV (PLWH) in Mbarara, Uganda; St. Petersburg, Russia; and Boston, Massachusetts. We conducted secondary analyses of baseline data collected from three cohorts in the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) consortium. We used multiple logistic regression models to evaluate the association between gender and heavy drinking (defined in combination with self-report and phosphatidylethanol [PEth]) within each cohort. In unadjusted logistic regression models, we found no significant association between gender and heavy drinking in Russia or Boston. In Uganda, women were less likely than men to engage in heavy drinking (odds ratio = 0.38, 95% CI [0.26, 0.58], p <.01). These findings were invariant to adjustment for covariates. We did not detect associations between gender and heavy drinking in cohorts of PLWH in Russia or Boston, suggesting that heavy drinking may be as common in women living with HIV as in men living with HIV in these locations. Although these cohorts were enriched with heavy drinking participants, which limits broad extrapolation to PLWH in those settings, nonetheless the findings are concerning given the significant morbidity associated with alcohol use among PLWH and women in particular.

Association between HIV infection and hypertension: a global systematic review and meta-analysis of cross-sectional studies

BackgroundImproved access to effective antiretroviral therapy has meant that people living with HIV (PLHIV) are surviving to older ages. However, PLHIV may be ageing differently to HIV-negative individuals, with dissimilar burdens of non-communicable diseases, such as hypertension. While some observational studies have reported a higher risk of prevalent hypertension among PLHIV compared to HIV-negative individuals, others have found a reduced burden. To clarify the relationship between HIV and hypertension, we identified observational studies and pooled their results to assess whether there is a difference in hypertension risk by HIV status.MethodsWe performed a global systematic review and meta-analysis of published cross-sectional studies that examined hypertension risk by HIV status among adults aged > 15 (PROSPERO: CRD42019151359). We searched MEDLINE, EMBASE, Global Health and Cochrane CENTRAL to August 23, 2020, and checked reference lists of included articles. Our main outcome was the risk ratio for prevalent hypertension in PLHIV compared to HIV-negative individuals. Summary estimates were pooled with a random effects model and meta-regression explored whether any difference was associated with study-level factors.ResultsOf 21,527 identified studies, 59 were eligible (11,101,581 participants). Crude global hypertension risk was lower among PLHIV than HIV-negative individuals (risk ratio 0.90, 95% CI 0.85–0.96), although heterogeneity between studies was high (I2 = 97%, p < 0.0001). The relationship varied by continent, with risk higher among PLHIV in North America (1.12, 1.02–1.23) and lower among PLHIV in Africa (0.75, 0.68–0.83) and Asia (0.77, 0.63–0.95). Meta-regression revealed strong evidence of a difference in risk ratios when comparing North American and European studies to African ones (North America 1.45, 1.21–1.74; Europe 1.20, 1.03–1.40).ConclusionsOur findings suggest that the relationship between HIV status and prevalent hypertension differs by region. The results highlight the need to tailor hypertension prevention and care to local contexts and underscore the importance of rapidly optimising integration of services for HIV and hypertension in the worst affected regions. The role of different risk factors for hypertension in driving context-specific trends remains unclear, so development of further cohorts of PLHIV and HIV-negative controls focused on this would also be valuable.

Factors associated with incidence of stroke and heart failure among people living with HIV in Ghana: Evaluating Vascular Event Risk while on Long-Term Antiretroviral Suppressive Therapy (EVERLAST) Study.

People living with HIV (PLWH) have a two‐fold higher risk of cardiovascular diseases (CVDs) compared with HIV‐negative populations. Although 70% of the global HIV population reside in Africa, data on CVD outcomes among PLWH are scarce. We seek to evaluate factors associated with incidence of stroke and heart failure in a prospective cohort of Ghanaian PLWH. We followed up a cohort of PLWH on antiretroviral therapy for 12 months to assess rates of clinically adjudicated stroke, and heart failure. We calculated incidence rates of events/1000 person‐years and fitted Cox proportional hazards regression models to identify factors associated with incident stroke and heart failure as a combined outcome measure and as separate outcome measures. Among 255 participants, the mean age was 46 years and 211 (82.7%) were female. The participants contributed 245 years of follow‐up data with mean follow‐up duration of 11.5 months. There were three incident strokes giving an incidence rate of 12.24 per 1000 person‐years (95% CI: 3.13–33.33) and two heart failure events with an incidence rate of 8.16 (95%CI: 1.37–26.97) per 1000 py. The combined event rate was 20.41 (95% CI: 7.48–45.24) per 1000 py. Being hypertensive was associated with aHR of 8.61 (1.32–56.04) of the combined outcome while each 100 cells/mm3 rise in CD4 count was associated with aHR of 0.56 (0.35–0.88). Carotid bulb intimal media thickness was independently associated with stroke occurrence with aHR of 12.23 (1.28–117.07). People living with HIV on long‐term cART in this Ghanaian sample have high rates of clinically adjudicated cardiovascular diseases driven by uncontrolled hypertension and persisting immunosuppression. Integration of CVD care into routine HIV management may help alleviate this untoward confluence of rising CVDs among PLWH.

Associations between Circulating MicroRNAs and Measures of Insulin/Glucose Dynamics in People Living with HIV with Dysglycemia

People living with HIV (PLWH) have near normal life expectancies with advances in antiretroviral therapy, but with the increasing average age, comorbid conditions create a new health burden for this population. Insulin resistance and type II diabetes are significantly higher in PLWH. microRNAs (miRs) are small non-coding RNAs that alter protein expression, and dysregulated expression of multiple miRs are implicated in altered insulin/glucose dynamics. There is increasing interest in using miRs as non-invasive biomarkers of pathophysiological states since most miRs are found in circulation and can be traced back to the cell type where they are either actively secreted or released during cell death. In this study, we aimed to identify circulating miRs that are associated with measures of insulin/glucose dynamics in PLWH with dysglycemia. PLWH (N=98, 68 male) with fasting plasma glucose between 95-124 mg/dL were enrolled in the parent ALIVE-Ex study provided their informed consent. Anthropometric measurements were taken along with adiponectin and an oral glucose tolerance test (OGTT) where glucose, insulin, and C-peptide were measured at 0, 1, and 2 hours. Average participant age was 52 ± 10 years, and average BMI was 27.7 ± 6.8 kg/m2. Total RNA was isolated from plasma (0h) and absolute miR expression was determined. miRs were selected based on their role in skeletal muscle (miR133a, miR-206), pancreatic β-cells (miR-375), adipose tissue (miR-let-7b), and liver (miR-20a). miR expression was correlated to measures of insulin/glucose dynamics using Spearman correlations. Multiple regression analyses were completed to control for sex, age, and BMI. Additional regression analyses combining miRs that significantly added to models (p<0.05) were used to improve predictions of insulin/glucose measures. miR-20a was positively correlated with glucose-2h (p<0.01) and this association remained significant when controlling for sex, age, and BMI. miR-375 was positively correlated with adiponectin (p<0.05); however, the association was not significant when controlling for sex, age, and BMI which were all significantly associated (p<0.01) with adiponectin. miR-206, 133a, and let-7b were not significantly correlated with any insulin/glucose measures. Combining miR-20a and miR-375 improved the prediction (R=0.42, p<0.0001) of increased glucose levels (2h) compared with miR-20a alone (R=0.30, p<0.01). In this cohort of PLWH with dysglycemia, our results indicate that only miR-375 and miR-20a significantly correlated with glucose/insulin measures. miR-375 is important for maintaining β-cell mass and was positively correlated with adiponectin, but sex, age, and BMI are stronger predictors of adiponectin. miR-20a is implicated in liver function and regulates hepatic glycogen synthesis, and the increased plasma miR-20a seen with higher plasma glucose levels could indicate hepatic dysregulation. Combining miR-20a and miR-375 led to improved predictions indicating that combining expression of multiple circulating miRs into a composite score could be utilized as an indicator of altered insulin/glucose dynamics in PLWH.

Recreational Drug Use in People Living with HIV in Spain: Factors Associated with Drug Use and the Impact on Clinical Outcomes

We analysed the impact of recreational drug use (RDU) on different outcomes in people living with HIV (PLHIV). A multicentre retrospective cohort study was performed with two cohorts of PLHIV included: people using recreational drugs (PURD) vs. people not using recreational drugs (PNURD). Overall, 275 PLHIV were included. RDU was associated with men having sex with men (OR 4.14, 95% CI [1.14, 5.19]), previous sexually transmitted infections (OR 4.00, 95% CI [1.97, 8.13]), and current smoking (OR 2.74, 95% CI [1.44, 5.19]). While the CD4/CD8 ratio increased amongst PNURD during the follow-up year, it decreased amongst PURD (p = 0.050). PURD presented lower scores of self-reported and multi-interval antiretroviral adherence (p = 0.017, and p = 0.006, respectively), emotional well-being (p < 0.0001), and regular follow-up (p = 0.059), but paid more visits to the emergency unit (p = 0.046). RDU worsens clinical, immunological, and mental health outcomes amongst PLHIV.

Late presentation for HIV remains a major health issue in Spain: Results from a multicenter cohort study, 2004-2018.

ObjectivesWith the purpose of reducing the well-known negative impact of late presentation (LP) on people living with HIV (PLWH), guidelines on early HIV diagnosis were published in 2014 in Spain, but since then no data on LP prevalence have been published. To estimate prevalence and risk factors of LP and to evaluate their impact on the development of clinical outcomes in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) during 2004–2018.MethodsCoRIS is an open prospective multicenter cohort of PLWH, adults, naive to ART at entry. LP was defined as HIV diagnosis with CD4 count ≤350 cells/μL or an AIDS defining event (ADE). Multivariable Poisson regression models were used to estimate both prevalence ratios (PR) for the association of potential risk factors with LP and Incidence rate ratios (IRRs) for its impact on the development of the composite endpoint (first ADE, first serious non-AIDS event [SNAE] or overall mortality).Results14,876 individuals were included. Overall, LP prevalence in 2004–2018 was 44.6%. Risk factors for LP included older age, having been infected through injection drug use or heterosexual intercourse, low educational level and originating from non-European countries. LP was associated with an increased risk of the composite endpoint (IRR: 1.34; 95%CI 1.20, 1.50), ADE (1.39; 1.18, 1.64), SNAE (1.22; 1.01, 1.47) and mortality (1.71; 1.41, 2.08).ConclusionsLP remains a health problem in Spain, mainly among certain populations, and is associated with greater morbidity and mortality. Public policies should be implemented to expand screening and early diagnosis of HIV infection, for a focus on those at greatest risk of LP.

Types of Stroke Among People Living With HIV in the United States.

Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes. CNICS, a U.S. multisite clinical cohort of PLWH in care. We implemented a centralized adjudication stroke protocol to identify stroke type, subtype, and precipitating conditions identified as direct causes including infection and illicit drug use in a large diverse HIV cohort. Among 26,514 PLWH, there were 401 strokes, 75% of which were ischemic. Precipitating factors such as sepsis or same-day cocaine use were identified in 40% of ischemic strokes. Those with precipitating factors were younger, had more severe HIV disease, and fewer traditional stroke risk factors such as diabetes and hypertension. Ischemic stroke subtypes included cardioembolic (20%), large vessel atherosclerosis (13%), and small vessel (24%) ischemic strokes. Individuals with small vessel strokes were older, were more likely to have a higher current CD4 cell count than those with cardioembolic strokes and had the highest mean blood pressure of the ischemic stroke subtypes. Ischemic stroke, particularly small vessel and cardioembolic subtypes, were the most common strokes among PLWH. Traditional and HIV-related risk factors differed by stroke type/subtype. Precipitating factors including infections and drug use were common. These results suggest that there may be different biological phenomena occurring among PLWH and that understanding HIV-related and traditional risk factors and in particular precipitating factors for each type/subtype may be key to understanding, and therefore preventing, strokes among PLWH.

Weight gain before and after switch from TDF to TAF in a U.S. cohort study

IntroductionAlthough weight gain has been reported with the use of integrase strand transfer inhibitors (InSTI), concurrent use of tenofovir alafenamide (TAF) has been implicated in recent studies. This study examined weight changes in people living with HIV (PLWH) who switched from tenofovir disoproxil fumarate (TDF) to TAF, to clarify the relative contribution to weight gain of core agents versus TDF to TAF switch.MethodsAntiretroviral‐experienced, virologically suppressed PLWH in the U.S. OPERA cohort were included if they switched from TDF to TAF (5NOV2015‐28FEB2019) and either maintained all other antiretrovirals or switched from a non‐InSTI to an InSTI. Linear mixed models were used to assess weight changes before/after the switch to TAF (restricted cubic splines on time) and rates of change over time (linear splines on time, based on the shape of the weight change curves). Changes in weight on TDF or TAF were assessed among those who maintained other antiretrovirals (overall, by core class), and those who maintained an InSTI or switched to an InSTI (by core agent). All models were adjusted for age, sex, race, (age‐sex, race‐sex interactions), BMI, CD4 cell count, endocrine disorders and concurrent medications that could affect weight.ResultsA total of 6908 PLWH were included, with 5479 maintaining all other antiretrovirals (boosted protease inhibitor: 746, non‐nucleoside reverse transcriptase inhibitor: 1452, InSTI: 3281) and 1429 switching from a non‐InSTI to an InSTI (elvitegravir/cobicistat: 1120, dolutegravir: 174, bictegravir: 129). In adjusted models, modest weight gain was observed over time on TDF for most (0.24 to 0.71 kg/year); raltegravir was the exception with weight loss. Switching to TAF was associated with early, pronounced weight gain for all (1.80 to 4.47 kg/year). This effect with TAF switch was observed both in PLWH maintaining other antiretrovirals and those switching to an InSTI, regardless of which InSTI agent was used. Weight gain tended to slow down or plateau approximately nine months after switch to TAF.ConclusionsIn this large, diverse U.S. cohort of PLWH, switching from TDF to TAF was associated with pronounced weight gain immediately after switch, regardless of the core class or core agent, suggesting an independent effect of TAF on weight gain.

Implementation of a Mobile Health Strategy to Improve Linkage to and Engagement with HIV Care for People Living with HIV, Tuberculosis, and Substance Use in Irkutsk, Siberia.

In Irkutsk, Siberia, there is a high prevalence of HIV and tuberculosis (TB) coinfection. Mobile health (mHealth) strategies have shown promise for increasing linkage to and engagement in care for people living with HIV (PLWH) in other contexts. We evaluated outcomes for a cohort of PLWH, TB, and substance use in Irkutsk after participation in a multi-feature mHealth intervention called MOCT. Sixty patients were enrolled during hospitalization for TB. We evaluated participant app usage, linkage to HIV care postdischarge, perception of self-efficacy related to HIV care, and HIV-related clinical outcomes at 6 months. We also performed an exploratory analysis to compare a subset of 49 patients with a pre-intervention cohort matched for age and gender. Participants demonstrated engagement with app features examined at 6 months. The majority linked to HIV care by 6 months (83%). Self-scoring of confidence in ability to communicate with HIV providers improved from baseline (median score 8, scale 1–10) to 6 months (10, p = 0.004). A higher proportion of the MOCT subset refilled antiretroviral therapy (69% vs. 43% in pre-intervention cohort, p = 0.01), with fewer deaths in the MOCT subset at 6 months (1 death vs. 10 deaths in pre-intervention cohort, p = 0.02) and a decreased likelihood of developing the composite outcome of death/failure to achieve viral suppression at 6 months (adjusted odds ratio = 0.33, p = 0.029). This study demonstrates preliminary intervention uptake and improvement in short-term outcomes for an urban cohort of PLWH, TB, and substance use enrolled in a multi-feature mHealth intervention, a novel strategy for the context.Clinical Trial Registration Number: NCT03819374.

A qualitative investigation of HIV treatment dispensing models and impacts on adherence among people living with HIV who use drugs.

Antiretroviral therapy (ART) dispensing is strongly associated with treatment adherence. Among illicit drug-using populations, whom experience greater structural barriers to adherence, directly administered antiretroviral therapy (DAAT) is often regarded as a stronger predictor of optimal adherence over self-administered medications. In Vancouver, Canada, people living with HIV (PLHIV) who use drugs and live in low-income housing are a critical population for treatment support. This group is typically able to access two key DAAT models, daily delivery and daily pickup, in addition to ART self-administration. This ethno-epidemiological qualitative study explores how key dispensing models impact ART adherence among PLHIV who use drugs living in low-income housing, and how this is framed by structural vulnerability. Semi-structured interviews lasting 30–45 minutes were conducted between February and May 2018 with 31 PLHIV who use drugs recruited from an ongoing prospective cohort of PLHIV who use drugs. Interviews were audio-recorded, transcribed verbatim, and analyzed using QSR International’s NVivo 12 software. Interviews focused on housing, drug use, and HIV management. Models that constrained agency were found to have negative impacts on adherence and quality of life. Treatment interruptions were framed by structural vulnerabilities (e.g., housing vulnerability) that impacted ability to maintain adherence under certain dispensing models, and led participants to consider other models. Participants using DAAT models which accounted for their structural vulnerabilities (e.g., mobility issues, housing instability), credited these models for their treatment adherence, but also acknowledged factors that constrained agency, and the negative impacts this could have on both adherence, and quality of life. Being able to integrate ART into an established routine is key to supporting ART adherence. ART models that account for the structural vulnerability of PLHIV who use drugs and live in low-income housing are necessary and housing-based supports could be critical, but the impacts of such models on agency must be considered to ensure optimal adherence.