Opioid misuse among persons with HIV engaged in care in the Southeastern US

The prevalence of opioid misuse by people living with HIV (PLWH) during the current US opioid epidemic has not been fully described. Among a cohort of persons engaged in HIV care in North Carolina, we examined the prevalence of and risk factors for opioid misuse, defined as self-reported “street” opioid use (e.g., heroin) or nonmedical prescription opioid use on a patient reported outcomes survey. Recent (past three-month) opioid misuse among 1,440 PLWH in care 2012–2017 was 2% (95% CI 2-3%) and lifetime misuse 15% (13-16%). Persons reporting lifetime or recent misuse more commonly had hepatitis C and reported injecting drugs. In multivariable logistic regression models, male-to-male sexual contact was inversely associated with recent or lifetime misuse. White/non-Hispanic race/ethnicity was associated with lifetime misuse and CD4 count and viral load were not associated with opioid misuse. Among 32 persons reporting recent misuse, 81% had a contemporaneous viral load <50 copies/mL. In this cohort of PLWH engaged in care, recent opioid misuse prevalence was similar to general population estimates. Assessments of opioid misuse among PLWH not in care are urgently needed to fully characterize the impact of opioids on all PLWH

Increased Persistence of Initial Treatment for HIV Infection with Modern Antiretroviral Therapy

Background: Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic responses with initial ART according to the class of anchor agent used. Setting: An observational clinical cohort study in the Southeastern United States. Methods: All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included. Separate time-to-event analyses with regimen discontinuation and virologic failure as outcomes were used, including Kaplan-Meier survival curves and adjusted Cox proportional hazards models. Results: One thousand six hundred twenty-four patients were included (median age of 37 years at baseline, 28% women, 60% African American, and 28% white). Eleven percent initiated integrase strand transfer inhibitor (INSTI), 33% non-nucleoside reverse transcriptase inhibitor (NNRTI), 20% boosted protease inhibitor, 27% other, and 9% NRTI only regimens. Compared with NNRTI-containing regimens, INSTI-containing regimens had an adjusted hazard ratio of 0.49 (95% confidence interval, 0.35 to 0.69) for discontinuation and 0.70 (95% confidence interval, 0.46 to 1.06) for virologic failure. All other regimen types were associated with increased rates of discontinuation and failure compared with NNRTI. Conclusions: Initiating ART with an INSTI-containing regimen was associated with lower rates of regimen discontinuation and virologic failure

New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations

OBJECTIVE: To estimate the prevalence of HIV drug resistance over time and identify risk factors for multiclass resistance. DESIGN: Prospective clinical cohort of HIV-infected patients at the University of North Carolina. METHODS: Among antiretroviral therapy (ART)-experienced patients in care 2000-2016, we estimated annual prevalences of cumulative resistance, defined as at least one major mutation by drug class. Clinical data and multiple imputation were used when genotypic data were missing, and mutations were carried forward in time. We estimated resistance odds ratios comparing characteristics of patients in care in 2016. RESULTS: A total of 3682 patients contributed 23 169 person-years. Prevalence of at least one major resistance mutation, irrespective of viral suppression, peaked in 2005 with 49% (95% confidence interval 46, 52) and decreased to 38% (35, 40) in 2016. Resistance to nucleoside reverse transcriptase inhibitors, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors also peaked in 2005-2007 and decreased to 28 (26, 31), 14 (12, 16), and 27% (24, 29) in 2016, respectively. In 2016, prevalence of integrase strand transfer inhibitor (INSTI) resistance was 2% (1, 3) and triple-class resistance 10% (9, 12). Over the study period, cumulative resistance was frequent among patients with detectable viremia, but uncommon among patients initiating ART post-2007. Among 1553 patients in care in 2016, ART initiation at an older age, with an INSTI, and with higher CD4 cell counts were associated with resistance to fewer or no classes. CONCLUSION: Prevalence of resistance to older ART classes has decreased in the last 10 years in this clinical cohort, whereas INSTI resistance has increased but remained very low. Patients with viremia continue to have a high burden of resistance even if they initiated ART recently

Effectiveness of integrase strand transfer inhibitors among treatment-experienced patients in a clinical setting

Objective:Characterize virologic and immunologic outcomes of INSTI-based antiretroviral therapy (ART) in experienced patients with and without virologic failure.Design:Prospective clinical cohort.Methods:ART-experienced, INSTI-naive participants in the University of North Carolina Center for AIDS Research HIV Clinical Cohort (UCHCC) initiating an INSTI-containing regimen 2007-2016 were followed from INSTI initiation (baseline) to the earliest of: outcome of interest, loss to follow-up (LTFU, 1 year without clinical visit), or death. Outcomes of interest were virologic failure (first of two consecutive viral loads at least 200 copies/ml more than 2 weeks apart, or one viral load ≥200 before LTFU) and immune recovery (first CD4+ ≥500 cells/μl). Patients with baseline viral load at least 50 copies/ml were given 24 weeks before meeting virologic failure criteria. Kaplan-Meier curves and Cox proportional hazards models compared INSTI regimens and patient characteristics.Results:Of 773 patients, 32% were women, 59% African-American, and 42% had a viral load at least 50 copies/ml at INSTI initiation. After 2 years, 5% of patients with baseline viral load less than 50 copies/ml experienced virologic failure, compared with 35% of patients with baseline viral load at least 50 copies/ml (P &lt; 0.01). Among patients with baseline viral load less than 50 copies/ml, dolutegravir/NRTIs was associated with longer time to virologic failure [adjusted hazard ratio (aHR) 0.11, 95% confidence interval (CI) 0.01-0.80], whereas among patients with baseline viral load at least 50 copies/ml, raltegravir/NRTIs was associated with longer time to virologic failure (aHR 0.35, 95% CI 0.18-0.68), both compared with elvitegravir/NRTIs. After 5 years suppressed, irrespective of baseline viral load, 61% of patients experienced immune recovery.Conclusion:In this cohort, INSTI-containing regimens led to low virologic failure rates in patients switching ART while suppressed. Viremic patients initiating INSTIs were at high risk of virologic failure during follow-up

Hospitalization rates and outcomes among persons living with human immunodeficiency virus in the southeastern united states, 1996-2016

Background. Antiretroviral therapy (ART) advances, aging, and comorbidities impact hospitalizations in human immunodeficiency virus (HIV)-positive populations. We examined temporal trends and patient characteristics associated with hospitalization rates and outcomes. Methods. Among patients in the University of North Carolina Center for AIDS Research HIV Clinical Cohort receiving care during 1996-2016, we estimated annual hospitalization rates, time to inpatient mortality or live discharge, and 30-day readmission risk using bivariable Poisson, Fine-Gray, and log-binomial regression models. Results. The 4323 included patients (29% women, 60% African American) contributed 30 007 person-years. Overall, the hospitalization rate per 100 person-years was 34.3 (95% confidence interval [CI], 32.4-36.4) with a mean annual change of -3% (95% CI, -4% to -2%). Patients who were black (vs white), older, had HIV RNA >400 copies/mL, or had CD4 count .05 for both 2010-2016 and 2003-2009 vs 1996-2002), and higher among black patients, those with detectable HIV RNA, and those with lower CD4 cell counts (all P < .05). Higher inpatient mortality was associated with older age and lower CD4 cell count (both P < .05). Conclusions. Hospitalization rates decreased from 1996 to 2016, but high readmissions persisted. Older patients, those of minority race/ethnicity, and those with uncontrolled HIV experienced higher rates and worse hospitalization outcomes. These findings underscore the importance of early ART and care engagement, particularly at hospital discharge

Acute HIV infection and CD4/CD8 ratio normalization after antiretroviral therapy initiation

Background:We estimated the effect of initiating virologically suppressive antiretroviral therapy (ART) during acute HIV infection versus chronic HIV infection (AHI vs. CHI) on CD4/CD8 ratio normalization.Setting:A prospective clinical cohort study.Methods:We included patients initiating ART with AHI and CHI between 2000 and 2015 and compared time from ART initiation to the first normal CD4/CD8 ratio (defined as CD4/CD8 ≥1) using Kaplan-Meier curves and multivariable Cox proportional hazards models. Patient time was censored at virologic failure, lost to follow-up, or death. We also characterized CD4, CD8, and CD4/CD8 trajectories over the first 3 years of ART.Results:The 1198 patients were 27% female and 60% African American, with a median age of 37 years (interquartile range 28-47) at ART initiation. The 83 AHI patients were more likely male, younger, and of white race, than CHI patients. After 2 years of suppressive ART, 70% of AHI patients achieved a normal CD4/CD8 ratio, compared to 6%-38% of CHI patients, with greater likelihood of normalization at higher baseline CD4 counts. Time to normalization was shortest among AHI patients, followed by CHI patients with higher baseline CD4. The adjusted hazard ratio for time to normalization for AHI patients compared to CHI patients with baseline CD4 >350 was 4.33 (95% CI: 3.16 to 5.93). Higher baseline CD4/CD8 ratio was also associated with time to normalization (adjusted hazard ratio 1.54; 1.46, 1.63, per 0.1 increase in ratio).Conclusions:Initiating ART during AHI at higher baseline CD4 cell counts and CD4/CD8 ratios was associated with shorter time to CD4/CD8 ratio normalization

Mental health and substance use screening in HIV primary care before and during the early COVID-19 pandemic

Background: Mental health and substance use disorders disproportionately affect people with HIV (PWH), and may have been exacerbated during COVID-19. The Promoting Access to Care Engagement (PACE) trial was designed to assess the effectiveness of electronic screening for mental health and substance use in HIV primary care and enrolled PWH from October 2018 to July 2020. Our objective here was to compare screening rates and results for PWH before (October 2018 – February 2020) and early in the COVID-19 pandemic (March-July 2020). Methods: Adult (≥ 18 years) PWH from 3 large HIV primary care clinics in a US-based integrated healthcare system were offered electronic screening online or via in-clinic tablet computer every 6 months. Screening completion and results (for depression, suicidal ideation, anxiety, and substance use) were analyzed using logistic regression with generalized estimating equations to estimate prevalence ratios (PR) before and after the start of the regional COVID-19 shelter-in-place orders on March 17, 2020. Models adjusted for demographics (age, sex, race/ethnicity), HIV risk factors (men who have sex with men, injection drug use, heterosexual, other), medical center, and modality of screening completion (online or tablet). We conducted qualitative interviews with providers participating in the intervention to evaluate how the pandemic impacted patient care. Results: Of 8,954 eligible visits, 3,904 completed screenings (420 during COVID, 3,484 pre-COVID), with lower overall completion rates during COVID (38% vs. 44%). Patients completing screening during COVID were more likely to be White (63% vs. 55%), male (94% vs. 90%), and MSM (80% vs., 75%). Adjusted PRs comparing COVID and pre-COVID (reference) were 0.70 (95% CI), 0.92 (95% CI), and 0.54 (95% CI) for tobacco use, any substance use, and suicidal ideation, respectively. No significant differences were found by era for depression, anxiety, alcohol, or cannabis use. These results were in contrast to provider-reported impressions of increases in substance use and mental health symptoms. Conclusion: Findings suggest PWH had modest declines in screening rates early in the COVID-19 pandemic which may have been affected by the shift to telemedicine. There was no evidence that mental health problems and substance use increased for PWH in primary care. Trial registration: NCT03217058 (First registration date: 7/13/2017); https://clinicaltrials.gov/ct2/show/NCT03217058

COVID-19 symptoms at time of testing and association with positivity among outpatients tested for SARS-CoV-2

Introduction Symptoms associated with SARS-CoV-2 infection remain incompletely understood, especially among ambulatory, non-hospitalized individuals. With host factors, symptoms predictive of SARS-CoV-2 could be used to guide testing and intervention strategies. Methods Between March 16 and September 3, 2020, we examined the characteristics and symptoms reported by individuals presenting to a large outpatient testing program in the Southeastern US for nasopharyngeal SARS-CoV-2 RNA RT-PCR testing. Using self-reported symptoms, demographic characteristics, and exposure and travel histories, we identified the variables associated with testing positive using modified Poisson regression. Results Among 20,177 tested individuals, the proportion positive was 9.4% (95% CI, 9.0–9.8) and was higher for men, younger individuals, and racial/ethnic minorities (all P<0.05); the positivity proportion was higher for Hispanics (26.9%; 95% CI. 24.9–29.0) compared to Blacks (8.6%; 95% CI, 7.6–9.7) or Whites (5.8%; 95% CI, 5.4–6.3). Individuals reporting contact with a COVID-19 case had the highest positivity proportion (22.8%; 95% CI, 21.5–24.1). Among the subset of 8,522 symptomatic adults who presented for testing after May 1, when complete symptom assessments were performed, SARS-CoV-2 RNA PCR was detected in 1,116 (13.1%). Of the reported symptoms, loss of taste or smell was most strongly associated with SARS-CoV-2 RNA detection with an adjusted risk ratio of 3.88 (95% CI, 3.46–4.35). The presence of chills, fever, cough, aches, headache, fatigue and nasal congestion also significantly increased the risk of detecting SARS-CoV-2 RNA, while diarrhea or nausea/vomiting, although not uncommon, were significantly more common in those with a negative test result. Symptom combinations were frequent with 67.9% experiencing ≥4 symptoms, including 19.8% with ≥8 symptoms; report of greater than three symptoms increased the risk of SARS-CoV-2 RNA detection. Conclusions In a large outpatient population in the Southeastern US, several symptoms, most notably loss of taste or smell, and greater symptom burden were associated with detection of SARS-CoV-2 RNA. Persons of color and those with who were a contact of a COVID-19 case were also more likely to test positive. These findings suggest that, given limited SARS-CoV-2 testing capacity, symptom presentation and host characteristics can be used to guide testing and intervention prioritization

Racial, ethnic, and gender disparities in hospitalizations among persons with HIV in the United States and Canada, 2005-2015

Objective: To examine recent trends and differences in all-cause and cause-specific hospitalization rates by race, ethnicity, and gender among persons with HIV (PWH) in the United States and Canada. Design: HIV clinical cohort consortium. Methods: We followed PWH at least 18 years old in care 2005-2015 in six clinical cohorts. We used modified Clinical Classifications Software to categorize hospital discharge diagnoses. Incidence rate ratios (IRR) were estimated using Poisson regression with robust variances to compare racial and ethnic groups, stratified by gender, adjusted for cohort, calendar year, injection drug use history, and annually updated age, CD4+, and HIV viral load. Results: Among 27 085 patients (122 566 person-years), 80% were cisgender men, 1% transgender, 43% White, 33% Black, 17% Hispanic of any race, and 1% Indigenous. Unadjusted all-cause hospitalization rates were higher for Black [IRR 1.46, 95% confidence interval (CI) 1.32-1.61] and Indigenous (1.99, 1.44-2.74) versus White cisgender men, and for Indigenous versus White cisgender women (2.55, 1.68-3.89). Unadjusted AIDS-related hospitalization rates were also higher for Black, Hispanic, and Indigenous versus White cisgender men (all P < 0.05). Transgender patients had 1.50 times (1.05-2.14) and cisgender women 1.37 times (1.26-1.48) the unadjusted hospitalization rate of cisgender men. In adjusted analyses, among both cisgender men and women, Black patients had higher rates of cardiovascular and renal/genitourinary hospitalizations compared to Whites (all P < 0.05). Conclusion: Black, Hispanic, Indigenous, women, and transgender PWH in the United States and Canada experienced substantially higher hospitalization rates than White patients and cisgender men, respectively. Disparities likely have several causes, including differences in virologic suppression and chronic conditions such as diabetes and renal disease

Hospitalization Rates and Causes among Persons with HIV in the United States and Canada, 2005-2015

Background: To assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015. Methods: In 6 clinical cohorts, we followed PWH in care (≥1 outpatient CD4 count or HIV load [VL] every 12 months) and categorized ICD codes of primary discharge diagnoses using modified Clinical Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually updated age, CD4, and VL. Results: Among 28057 patients (125724 person-years), from 2005 to 2015, the median CD4 increased from 389 to 580 cells/μL and virologic suppression from 55% to 85% of patients. Unadjusted all-cause hospitalization rates decreased from 22.3 per 100 person-years in 2005 (95% confidence interval [CI], 20.6-24.1) to 13.0 in 2015 (95% CI, 12.2-14.0). Unadjusted rates decreased for almost all diagnostic categories. Adjusted rates decreased for all-cause, cardiovascular, and AIDS-defining conditions, increased for non-AIDS-defining infection, and were stable for most other categories. Conclusions: Among PWH with increasing CD4 counts and viral suppression, unadjusted hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals