Hepatitis C Treatment in People With HIV: Potential to Eliminate Disease and Disparity.

Access to direct acting antivirals (DAAs) may be associated with reductions in hepatitis C virus (HCV) viremia prevalence among people with human immunodeficiency virus (PWH). Among 3755 PWH, estimated HCV viremia prevalence decreased by 94.0% from 36% (95% confidence interval [CI], 27%-46%) in 2009 (pre-DAA era) to 2% (95% CI, 0%-4%) in 2021 (DAA era). Male sex, black race, and older age were associated with HCV viremia in 2009 but not in 2021. Injection drug use remained associated with HCV viremia in 2009 and 2021. Targeted interventions are needed to meet the HCV care needs of PWH who use drugs.

Joint effects of substance use disorders and recent substance use on HIV viral non-suppression among people engaged in HIV care in an urban clinic, 2014-2019.

AIMS: To estimate the joint effects of substance use disorder (SUD) and recent substance use on human immunodeficiency virus (HIV) non-suppression. DESIGN: Retrospective clinical cohort study with repeated observations within individuals. SETTING: Baltimore, Maryland, United States. PARTICIPANTS: 1881 patients contributed 10 794 observations. MEASUREMENTS: The primary independent variable was the combination of history of SUD and recent substance use. History of SUD was defined as any prior International Classification of Diseases 9/10 code for cocaine or opioid disorder. Recent substance use was defined as the self-report of cocaine or non-prescribed opioid use on the National Institute of Drug Abuse-modified Alcohol, Smoking and Substance Involvement Screening Test or clinician-documented cocaine or opioid use abstracted from the medical record. The outcome was viral non-suppression, defined as HIV RNA >200 copies/mL on the first viral load measurement within 1 year subsequent to each observation of substance use. We adjusted for birth sex, Black race, age, HIV acquisition risk factors, years in care and CD4 cell count. In secondary analyses, we also adjusted for depressive, anxiety and panic symptoms, cannabis use and cannabis use disorder. FINDINGS: On their first observation, 31% of patients had a history of an SUD and 18% had recent substance use. Relative to no history of SUD and no recent substance use, the 1-year fully adjusted risk difference (RD) for viral non-suppression associated with cocaine and opioid use disorder and recent substance use was 7.7% (95% CI = 5.3%-10.0%), the RD was 5.5% (95% CI = 1.2%-9.7%) for history of cocaine use disorder without recent substance use, and the RD was 4.6% (95% CI = 2.7%-6.5%) for recent substance use without a SUD. CONCLUSIONS: Substance use and substance use disorders appear to be highly prevalent among, and independently associated with, viral non-suppression among people with HIV.

The Testing Imperative: Why the US Ending the Human Immunodeficiency Virus (HIV) Epidemic Program Needs to Renew Efforts to Expand HIV Testing in Clinical and Community-Based Settings.

Data from several modeling studies demonstrate that large-scale increases in human immunodeficiency virus (HIV) testing across settings with a high burden of HIV may produce the largest incidence reductions to support the US Ending the HIV Epidemic (EHE) initiative's goal of reducing new HIV infections 90% by 2030. Despite US Centers for Disease Control and Prevention's recommendations for routine HIV screening within clinical settings and at least yearly screening for individuals most at risk of acquiring HIV, fewer than half of US adults report ever receiving an HIV test. Furthermore, total domestic funding for HIV prevention has remained unchanged between 2013 and 2019. The authors describe the evidence supporting the value of expanded HIV testing, identify challenges in implementation, and present recommendations to address these barriers through approaches at local and federal levels to reach EHE targets.

Alcohol consumption upon direct-acting antiviral therapy for hepatitis C among persons with human immunodeficiency virus in the United States.

BACKGROUND: Direct-acting antivirals (DAA) are highly effective against hepatitis C virus (HCV) infection among persons with human immunodeficiency virus (PWH). However, alcohol use post-DAA treatment poses a continued threat to the liver. Whether the focus on liver health alone during HCV treatment can impact alcohol consumption is unclear. Therefore, we examined the change in alcohol use among HCV-coinfected PWH who received DAA therapy by non-addiction medical providers. METHODS: In our longitudinal clinical cohort study, we identified HCV-coinfected PWH who received interferon-free DAA therapy between January 2014 and June 2019 in the Centers for AIDS Research Network of Integrated Clinical Systems. The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was the alcohol screening instrument. We used mixed-effects logistic regression models to estimate the longitudinal change in alcohol use upon DAA therapy. RESULTS: Among 738 HCV-coinfected PWH, 339 (46 %) reported any alcohol use at the end of HCV treatment, including 113 (15 %) with high-risk use (i.e., AUDIT-C ≥3 for women, ≥4 for men). Concurrently, 280 (38 %) PWH noted active drug use, and 357 (48 %) were currently smoking. We observed no changes in the odds of any alcohol or high-risk alcohol use over time with DAA therapy. Findings were similar in the PWH subgroup with a history of alcohol use before DAA treatment. CONCLUSIONS: For PWH with HCV, alcohol use did not change following interferon-free DAA treatment by non-addiction medical providers. Thus, clinicians should consider integrating targeted alcohol use interventions into HCV care to motivate reduced alcohol consumption and safeguard future liver health.

The relationship of alcohol and other drug use during the COVID-19 pandemic among people with or at risk of HIV; A cross-sectional survey of people enrolled in Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) cohorts.

BACKGROUND: Alcohol use during the COVID-19 pandemic increased. People living with HIV or at risk for HIV acquisition often have psycho-social and structural barriers or co-occurring substance use making them vulnerable to the adverse effects of alcohol. We describe factors associated with alcohol use during the COVID-19 pandemic in this group. METHODS: From May 2020 to February 2021, 1984 people enrolled in 6 existing cohort studies completed surveys about alcohol and other drug use during the COVID-19 pandemic. We describe the past-month prevalence of no alcohol use, low-risk use, and hazardous use. We use multinomial regression to describe factors associated with low-risk or hazardous alcohol use relative to no alcohol use. RESULTS: Forty-five percent of participants reported no alcohol use, 33% low-risk use, and 22% hazardous use in the past 30 days. Cannabis and stimulant use were associated with a higher prevalence of low-risk use relative to no use. Tobacco, stimulant, cannabis use and recent overdose were associated with a higher prevalence of hazardous use relative to no use. Substance use treatment and living with HIV were associated with a lower prevalence of low-risk or hazardous use relative to no use. CONCLUSIONS: Stimulant use was strongly associated with a higher prevalence of hazardous alcohol use while engagement in substance use treatment or living with HIV was associated with a lower prevalence. Ascertaining hazardous alcohol and other drug use, particularly stimulants, in clinical care could identify people at higher risk for adverse outcome and harm reduction counseling.

COVID-19 and the HIV continuum in people living with HIV enrolled in Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) cohorts.

BACKGROUND: The COVID-19 pandemic disrupted the normal delivery of HIV care, altered social support networks, and caused economic insecurity. People with HIV (PWH) are vulnerable to such disruptions, particularly if they have a history of substance use. We describe engagement in care and adherence to antiretroviral therapy (ART) for PWH during the pandemic. METHODS: From May 2020 to February 2021, 773 PWH enrolled in 6 existing cohorts completed 1495 surveys about substance use and engagement in HIV care during the COVID-19 pandemic. We described the prevalence and correlates of having missed a visit with an HIV provider in the past month and having missed a dose of ART in the past week. RESULTS: Thirteen percent of people missed an HIV visit in the past month. Missing a visit was associated with unstable housing, food insecurity, anxiety, low resiliency, disruptions to mental health care, and substance use including cigarette smoking, hazardous alcohol use, cocaine, and cannabis use. Nineteen percent of people reported missing at least one dose of ART in the week prior to their survey. Missing a dose of ART was associated with being a man, low resiliency, disruptions to mental health care, cigarette smoking, hazardous alcohol use, cocaine, and cannabis use, and experiencing disruptions to substance use treatment. CONCLUSIONS: Social determinants of health, substance use, and disruptions to mental health and substance use treatment were associated with poorer engagement in HIV care. Close attention to continuity of care during times of social disruption is especially critical for PWH.

Potential Effects of the Coronavirus Disease 2019 (COVID-19) Pandemic on Human Immunodeficiency Virus (HIV) Transmission: A Modeling Study in 32 US Cities.

BACKGROUND: The degree to which the 2019 novel coronavirus disease (COVID-19) pandemic will affect the US human immunodeficiency virus (HIV) epidemic is unclear. METHODS: We used the Johns Hopkins Epidemiologic and Economic Model to project HIV infections from 2020 to 2025 in 32 US metropolitan statistical areas (MSAs). We sampled a range of effects of the pandemic on sexual transmission (0-50% reduction), viral suppression among people with HIV (0-40% reduction), HIV testing (0-50% reduction), and pre-exposure prophylaxis use (0-30% reduction), and indexed reductions over time to Google Community Mobility Reports. RESULTS: Simulations projected reported diagnoses would drop in 2020 and rebound in 2021 or 2022, regardless of underlying incidence. If sexual transmission normalized by July 2021 and HIV care normalized by January 2022, we projected 1161 (1%) more infections from 2020 to 2025 across all 32 cities than if COVID-19 had not occurred. Among "optimistic" simulations in which sexual transmission was sharply reduced and viral suppression was maintained we projected 8% lower incidence (95% credible interval: 14% lower to no change). Among "pessimistic" simulations where sexual transmission was largely unchanged but viral suppression fell, we projected 11% higher incidence (1-21% higher). MSA-specific projections are available at www.jheem.org?covid. CONCLUSIONS: The effects of COVID-19 on HIV transmission remain uncertain and differ between cities. Reported diagnoses of HIV in 2020-2021 are likely to correlate poorly with underlying incidence. Minimizing disruptions to HIV care is critical to mitigating negative effects of the COVID-19 pandemic on HIV transmission.

What Will It Take to End HIV in the United States? : A Comprehensive, Local-Level Modeling Study.

BACKGROUND: The Ending the HIV Epidemic (EHE) initiative aims to reduce incident HIV infections by 90% over a span of 10 years. The intensity of interventions needed to achieve this for local epidemics is unclear. OBJECTIVE: To estimate the effect of HIV interventions at the city level. DESIGN: A compartmental model of city-level HIV transmission stratified by age, race, sex, and HIV risk factor was developed and calibrated. SETTING: 32 priority metropolitan statistical areas (MSAs). PATIENTS: Simulated populations in each MSA. INTERVENTION: Combinations of HIV testing and preexposure prophylaxis (PrEP) coverage among those at risk for HIV, plus viral suppression in persons with diagnosed HIV infection. MEASUREMENTS: The primary outcome was the projected reduction in incident cases from 2020 to 2030. RESULTS: Absent intervention, HIV incidence was projected to decrease by 19% across all 32 MSAs. Modest increases in testing (1.25-fold per year), PrEP coverage (5 percentage points), and viral suppression (10 percentage points) across the population could achieve reductions of 34% to 67% by 2030. Twenty-five percent PrEP coverage, testing twice a year on average, and 90% viral suppression among young Black and Hispanic men who have sex with men (MSM) achieved similar reductions (13% to 68%). Including all MSM and persons who inject drugs could reduce incidence by 48% to 90%. Thirteen of 32 MSAs could achieve greater than 90% reductions in HIV incidence with large-scale interventions that include heterosexuals. A web application with location-specific results is publicly available (www.jheem.org). LIMITATION: The COVID-19 pandemic was not represented. CONCLUSION: Large reductions in HIV incidence are achievable with substantial investment, but the EHE goals will be difficult to achieve in most locations. An interactive model that can help policymakers maximize the effect in their local environments is presented. PRIMARY FUNDING SOURCE: National Institutes of Health.

The Effect of Buprenorphine on Human Immunodeficiency Virus Viral Suppression.

BACKGROUND: Opioid use is prevalent among people living with human immunodeficiency virus (HIV; PLWH) and adversely affects HIV outcomes. We assessed the effect of buprenorphine (BUP) initiation on subsequent HIV viral loads. METHODS: We identified PLWH from the Johns Hopkins HIV Clinical Cohort who initiated BUP between 2002 and 2017. Poisson regression with robust variance was used to estimate the prevalence of viral suppression (<200 copies/mL) before and after BUP initiation. We matched individuals who initiated BUP with controls based on viral load measurement dates and used prior event rate ratio (PERR) methods to estimate the effect of BUP initiation on viral suppression. PERR methods account for unmeasured confounders. RESULTS: We identified 279 PLWH who initiated BUP. After BUP initiation, PLWH were more likely to be virally suppressed (prevalence ratio [PR], 1.19; 95% confidence interval [CI], 1.03-1.37). After matching PLWH who initiated BUP to controls and accounting for measured and unmeasured confounders, BUP initiation increased viral suppression for both those on antiretroviral therapy (ART) at baseline (PERR PR, 1.08; 95% CI, 1.00-1.18) and those not on ART at baseline (PR, 1.31; 95% CI, 1.10-1.61). CONCLUSIONS: Our results indicate that the initiation of BUP results in an increase in the probability of being virally suppressed after accounting for both measured and unmeasured confounders. Persons with opioid use disorder should initiate BUP to not only treat substance use but also to increase viral suppression allowing for treatment as prevention.

A comparison of cancer stage at diagnosis and treatment initiation between enrollees in an urban HIV clinic and SEER.

PURPOSE: A comparison of stage at cancer diagnosis and cancer treatment rates between people with HIV (PWH) and the general US population is needed to identify any disparities by HIV status. METHODS: We compared 236 PWH in clinical care diagnosed with cancer from 1997 to 2014 to a sample from NCI's Surveillance, Epidemiology and End Results (SEER) Program, presumed to be HIV negative. We performed G-computation using random forest methods to estimate stage and treatment percent differences (PD) by HIV. We conducted sensitivity analyses among non-AIDS-defining cancers (NADC), by sex and by CD4 ≤ 200 or > 200 cells/mm3. RESULTS: PWH were less likely to be diagnosed at localized stage (PD = - 16%; 95% CI - 21, - 11) and more likely to be diagnosed at regional stage (PD = 14%; 95% CI 8, 19) than those in SEER. Cancer treatment rates were 13% lower among PWH as compared to SEER (95% CI - 18, - 8). The difference in percent receiving cancer treatment was more pronounced for those with lower CD4 at cancer diagnosis (PD -15%; 95% CI - 27, - 6). Lower treatment rates were observed among NADC, males, and women with CD4 ≤ 200. CONCLUSION: Cancer care for PWH could be improved by diagnosis at earlier stages and increasing rates of cancer treatment.

Short Communication: Differences in 5-Year Survival After Cancer Diagnosis Between HIV Clinic Enrollees and the General U.S. Population.

A total of 236 people with HIV (PWH) with cancer diagnosed between 1997 and 2014 in the Johns Hopkins HIV Clinical Cohort (JHHCC) were compared with a sample from NCI's Surveillance, Epidemiology, and End Results (SEER) Program, presumed to be HIV negative. Using G-computation with random survival forest methods, we estimated 5-year restricted mean survival time (RMST) differences by HIV status. Sensitivity analyses were performed among non-AIDS defining cancers, males, females, and stratifying PWH by CD4 ≤ 200 or >200 cells/mm3 at cancer diagnosis. PWH with CD4 ≤ 200 cells/mm3 had decreased survival compared with those in SEER (-7 months; 95% CI = -13 to -2). Women with HIV and CD4 ≤ 200 cells/mm3 at cancer diagnosis had lower survival than SEER women (-10 months; 95% CI = -18 to -2). In the total population, there was no significant difference in 5-year RMST; however, women with HIV and low CD4 had higher mortality despite accounting for stage at diagnosis and first course of cancer treatment.

Immune Status and Associated Mortality After Cancer Treatment Among Individuals With HIV in the Antiretroviral Therapy Era.

Importance: Immunologic decline associated with cancer treatment in people with HIV is not well characterized. Quantifying excess mortality associated with cancer treatment-related immunosuppression may help inform cancer treatment guidelines for persons with HIV. Objective: To estimate the association between cancer treatment and CD4 count and HIV RNA level in persons with HIV and between posttreatment CD4 count and HIV RNA trajectories and all-cause mortality. Design, Setting, and Participants: This observational cohort study included 196 adults with HIV who had an incident first cancer and available cancer treatment data while in the care of The Johns Hopkins HIV Clinic from January 1, 1997, through March 1, 2016. The study hypothesized that chemotherapy and/or radiotherapy in people with HIV would increase HIV RNA levels owing to treatment tolerability issues and would be associated with a larger initial decline in CD4 count and slower CD4 recovery compared with surgery or other treatment. An additional hypothesis was that these CD4 count declines would be associated with higher mortality independent of baseline CD4 count, antiretroviral therapy use, and risk due to the underlying cancer. Data were analyzed from December 1, 2017, through April 1, 2018. Exposures: Initial cancer treatment category (chemotherapy and/or radiotherapy vs surgery or other treatment). Main Outcomes and Measures: Post-cancer treatment longitudinal CD4 count, longitudinal HIV RNA level, and all-cause mortality. Results: Among the 196 participants (135 [68.9%] male; median age, 50 [interquartile range, 43-55] years), chemotherapy and/or radiotherapy decreased initial CD4 count by 203 cells/µL (95% CI, 92-306 cells/µL) among those with a baseline CD4 count of greater than 500 cells/µL. The decline for those with a baseline CD4 count of no greater than 350 cells/µL was 45 cells/µL (interaction estimate, 158 cells/µL; 95% CI, 31-276 cells/µL). Chemotherapy and/or radiotherapy had no detrimental association with HIV RNA levels. After initial cancer treatment, every 100 cells/µL decrease in CD4 count resulted in a 27% increase in mortality (hazard ratio, 1.27; 95% CI, 1.08-1.53), adjusting for HIV RNA level. No significant increase in mortality was associated with a unit increase in log10 HIV RNA after adjusting for CD4 count (hazard ratio, 1.24; 95% CI, 0.94-1.65). Conclusions and Relevance: In this study, chemotherapy and/or radiotherapy was associated with significantly reduced initial CD4 count in adults with HIV compared with surgery or other treatment. Lower CD4 count after cancer treatment was associated with an increased hazard of mortality. Further research is necessary on the immunosuppressive effects of cancer treatment in adults with HIV and whether health care professionals must consider the balance of cancer treatment efficacy against the potential cost of further immunosuppression. Monitoring of immune status may also be helpful given the decrease in CD4 count after treatment and the already immunocompromised state of patients with HIV.

Tobacco Smoking, Substance Use, and Mental Health Symptoms in People with HIV in an Urban HIV Clinic.

The prevalence of tobacco smoking among people with HIV (PWH) ranges from 40% to 70%. Additionally, tobacco smoking is higher among low-income individuals, yet few studies have examined tobacco smoking in low socioeconomic status PWH. Using data from a cohort of PWH receiving care in an urban HIV clinic, we characterized factors associated with current and former smoking and with initiation/re-initiation and cessation of tobacco use. Among a study sample of 1,607 PWH, the prevalence of current smoking was 46.6% among men and 46.0% among women. Current smoking in men and women was associated with Medicaid insurance status, substance use, and panic symptoms. In women, but not men, hazardous alcohol use decreased the likelihood of quitting smoking and increased the risk of initiation/re-initiation. Smoking interventions for low-income, urban PWH may need to be tailored to address mental health and substance use comorbidities.

Do Symptoms of Depression Interact with Substance Use to Affect HIV Continuum of Care Outcomes?

Few studies examine how depression and substance use interact to affect HIV control. In 14,380 persons with HIV (PWH), we used logistic regression and generalized estimating equations to evaluate how symptoms of depression interact with alcohol, cocaine, opioid, and methamphetamine use to affect subsequent retention in care, maintaining an active prescription for ART, and consistent virologic suppression. Among PWH with no or mild depressive symptoms, heavy alcohol use had no association with virologic suppression (OR 1.00 [0.95-1.06]); among those with moderate or severe symptoms, it was associated with reduced viral suppression (OR 0.80 [0.74-0.87]). We found no interactions with heavy alcohol use on retention in care or maintaining ART prescription or with other substances for any outcome. These results highlight the importance of treating moderate or severe depression in PWH, especially with comorbid heavy alcohol use, and support multifaceted interventions targeting alcohol use and depression.

Measurement of Current Substance Use in a Cohort of HIV-Infected Persons in Continuity HIV Care, 2007-2015.

Accurate, routine measurement of recent illicit substance use is challenging. The Johns Hopkins Human Immunodeficiency Virus Clinical Cohort (Baltimore, Maryland) collects 2 imperfect but routine measurements of recent substance use: medical record review and self-interview. We used Bayesian latent class modeling to estimate sensitivity and specificity of each measurement as well as prevalence of substance use among 2,064 patients engaged in care during 2007-2015. Sensitivity of medical record review was higher than sensitivity of self-interview for cocaine and heroin use; posterior estimates ranged from 44% to 76% for cocaine use and from 39% to 67% for heroin use, depending on model assumptions and priors. In contrast, sensitivity of self-interview was higher than sensitivity of medical record review for any alcohol use, hazardous alcohol use, and cigarette smoking. Posterior estimates of sensitivity of self-interview were generally above 80%, 85%, and 87% for each substance, respectively. Specificity was high for all measurements. From one model, we estimated prevalence of substance use in the cohort to be 12.5% for cocaine, 9.3% for heroin, 48.5% for alcohol, 21.4% for hazardous alcohol, and 55.4% for cigarettes. Prevalence estimates from other models were generally comparable. Measurement error of substance use is nontrivial and should be accounted for in subsequent analyses.