Assessing HIV Care Outcomes Among Persons Who Use Drugs in Puerto Rico Before and After Hurricane Maria.

OBJECTIVES: To explore the health impacts of Hurricane Maria (HM) on HIV care outcomes among people living with HIV who use drugs. METHODS: Using data from an ongoing cohort study in San Juan, Puerto Rico (Proyecto PACTo), we measured differences in HIV care outcomes (viral load, viral suppression, and CD4 counts) before and after HM using assessments conducted at 6-month intervals. Generalized estimating equations were used to assess factors associated with HIV care outcomes. RESULTS: All HIV care outcomes showed a deterioration from pre-HM values to post-HM values (mean viral load increased, CD4 counts decreased, and rate of viral suppression decreased) after controlling for pre-HM sociodemographic and health characteristics. In addition to HM, age (aIRR = 1·01), being homeless (aIRR = 0·78) and having health insurance (aIRR = 1·6) were independently associated with viral suppression. PARTICIPANTS: 219 participants completed follow-up visits between April 2017 and January 2018, before and after HM. CONCLUSIONS: People living with HIV who use drugs in Puerto Rico experienced poorer HIV outcomes following HM. Socio-environmental factors contributing to these outcomes is discussed in the context of disaster response, recovery, and program planning.

Geographical Differences in the Self-Reported Functional Impairment of People With Human Immunodeficiency Virus (HIV) and Associations With Cardiometabolic Risk.

BACKGROUND: We sought to explore multinational differences in functional status by global burden of disease (GBD) regions in the REPRIEVE cohort. METHODS: REPRIEVE is a prospective, double-blind, randomized, placebo-controlled, multicenter, phase III primary cardiovascular prevention study of pitavastatin calcium vs placebo among people with human immunodeficiency virus (HIV, PWH) ages 40-75 on antiretroviral therapy (ART). GBD super regions were defined using World Health Organization classifications. Participants were categorized by impairment on the Duke Activity Status Instrument (DASI: none, some, moderate, severe). Logistic regression models examined risk factors and GBD regions associated with functional impairment. The association between functional impairment and cardiometabolic risk was also explored. RESULTS: Of 7736 participants, the majority were from high-income countries (n = 4065), were male (65%), and had received ART for ≥ 10 years. The median DASI score was 58.2 (interquartile range [IQR] 50.2, 58.2); 36% reported at least some impairment. In adjusted analyses, functional impairment was significantly more frequent among participants from Southeast/East Asia. Other factors associated with greater impairment included female sex, Black race, older age, current/former smoking, higher body mass index, use of ART for ≥ 10 years, and select ART regimens; differences were seen in risks across GBD regions. Functional impairment was associated with increased cardiometabolic risk. CONCLUSIONS: Over 1/3 of middle-aged and older PWH in a global cohort across diverse GBD regions demonstrate functional impairments. The associations between DASI and cardiometabolic risk suggest that a measure of functional status may improve risk prediction; these longitudinal associations will be further investigated over REPRIEVE trial follow-up.

A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial.

BACKGROUND: Despite widespread availability of direct-acting antivirals including generic formulations, limited progress has been made in the global adoption of hepatitis C virus (HCV) treatment. Barriers to treatment scale-up include availability and access to diagnostic and monitoring tests, health-care infrastructure, and requirement for frequent visits during treatment. METHODS: ACTG A5360 was a phase 4, open-label, single-arm trial across 38 sites in Brazil, South Africa, Thailand, Uganda, and the USA. Key inclusion criteria were age of 18 years or older, evidence of active HCV infection (HCV RNA >1000 IU/mL) and HCV treatment-naive; patients with compensated cirrhosis and HIV/HCV co-infection were included but their enrolment was capped. All participants received a fixed dose combination of oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. The minimal monitoring (MINMON) approach consisted of four components: (1) there was no pre-treatment genotyping; (2) the entire treatment course (84 tablets) was dispensed at entry; (3) there were no scheduled visits or laboratory monitoring; and (4) there were two points of remote contact, at week 4 for adherence and week 22, to schedule outcome assessment at week 24 (-2 weeks to +4 weeks). Participants who missed the week 24 window could return for a visit to assess treatment response any time before week 72. Unplanned visits for any reason were permissible before the week 24 visit. The primary efficacy outcome was sustained virological response (SVR), defined as HCV RNA less than the lower limit of quantification measured at least 22 weeks post-treatment initiation; the primary safety outcome was serious adverse events. The primary efficacy analysis included all participants who initiated treatment, using a missing=failure approach. The primary safety analysis included all participants who initiated treatment and had at least one post-treatment assessment. This trial is registered at ClinicalTrials.gov, NCT03512210. FINDINGS: Between Oct 22, 2018, and July 19, 2019, 400 participants were enrolled across all 38 sites; 399 initiated treatment. At the SVR assessment visit, 355 (89%) of 397 participants reported taking 100% of the trial medication during the 12-week treatment period; two patients did not have any follow-up visits after the entry visit and were excluded from the safety analyses. Overall, 379 of the 399 who initiated treatment had an SVR (95·0%, 95% CI 92·4-96·7). 14 (4%) of 397 participants reported serious adverse events between treatment initiation and week 28; none were treatment related or led to treatment discontinuation or death. 15 (4%) of 399 participants had unplanned visits; none were related to treatment. INTERPRETATION: In this diverse global population of people with HCV, the MINMON approach with sofosbuvir-velpatasvir treatment was safe and achieved SVR comparable to standard monitoring observed in real-world data. Coupled with innovative case finding strategies, this strategy could be crucial to the global HCV elimination agenda. FUNDING: US National Institutes of Health and Gilead Sciences.

Early immunologic response to mRNA COVID-19 vaccine in patients receiving biologics and/or immunomodulators.

Patients with immune conditions and immune-modifying therapies were excluded from the Covid-19 vaccine trials. Studies have shown conflicting response to different vaccines in persons receiving immune suppressors or biologics. The aim of this study is to evaluate humoral and cellular response to Covid-19 vaccines in patients with Inflammatory Bowel Disease (IBD) using biologic and/or immunomodulatory (IMM) therapies. Methods: Participants are adults with IBD receiving biologics or IMM planning to receive a Covid 19 vaccine. Cellular immunity (CD4+ and CD8+ T cell levels) with flow cytometry are measured at baseline and 2 weeks after each vaccine dose. Humoral immunity (antibody titers and neutralizing capacity,VNT%) is analyzed by ELISA at baseline, 2 weeks after each dose, and 6 and 12 months after vaccine. We present the early results of the first 19 subjects. The study is approved by the IRB. Results: 19 subjects (18 in biologics and 1 in IMM) who received 2 doses of the Pfizer-BioNTech vaccine are included. Total IgG antibodies increased 21.13 times after the first dose and 90 times after the second dose. VTN% increased 11.92 times after the first dose and 53.79 times after the second dose. When compared with a healthy control cohort, total IgG antibodies and VTN% were lower in the subjects after the first dose. After the second dose, IgG antibodies increased but remained lower than controls, but VTN% were similar to controls. CD4 and CD8 mean levels had an upward trend after vaccination. Conclusions: Neutralizing capacity response to the vaccine in subjects was similar to a healthy cohort in spite of lower increases in total IgG antibodies. The CD4 and CD8 results observed may support the capacity to mount an effective cellular response in patients on biologics. Larger studies are needed to determine vaccine efficacy in these patients.

Public Health Academic Alliance for COVID-19 Response: The Role of a National Medical Task Force in Puerto Rico.

Alliances between the government and academic communities can be a key component of the public health response to an emergency such as the coronavirus disease 2019 (COVID-19) pandemic. The Governor of Puerto Rico designated the Puerto Rico Medical Task Force (MTF) COVID-19 to provide direct guidance and evaluation of the government response to the epidemic in Puerto Rico. Several work groups were formed within the MTF to create protocols and provide evidence-based recommendations on different public health aspects. The collaboration between the academia and the government enhanced the Puerto Rican public health response and contributed to the reduction seen in the contagion curve. Healthcare services and hospitals have not reached their maximum patient care capacity and the death toll has been controlled. Incorporating a national MTF with members of the academia into the government structure was beneficial during the COVID-19 response in Puerto Rico. A similar strategy could serve as a model for other states or territories and countries in similar scenarios.

Brief Report: Effects of Low-Volume High-Intensity Interval Training in Hispanic HIV+ Women: A Nonrandomized Study.

BACKGROUND: Low cardiorespiratory fitness (CRF) is usually observed in people living with HIV. The effect of a low-volume high-intensity interval training (LV-HIIT) on CRF in HIV+ and HIV- Hispanic women was evaluated in this study. SETTING: A nonrandomized clinical trial with pre-test and post-test using a LV-HIIT intervention was conducted in the AIDS Clinical Trials Unit and the Puerto Rico Clinical and Translational Research Consortium at the University of Puerto Rico Medical Sciences Campus. METHODS: Twenty-nine HIV+ and 13 HIV- Hispanic women recruited from community-based programs and clinics, and able to engage in daily physical activities, volunteered to participate. Of these, 20 HIV+ (69%) and 11 HIV- (85%) completed the study and were included in the analyses. LV-HIIT consisted of 6-week, 3 d/wk, 8-10 high-intensity and low-intensity intervals on a cycle ergometer at 80%-90% of heart rate reserve. Main outcome measures were CRF (defined as VO2peak), peak workload, and time to peak exercise. RESULTS: Average peak workload and time to peak exercise increased after training (P < 0.05) in both groups. However, average CRF was significantly higher after training only in the HIV- group. Gains in CRF were observed in 100% of HIV- and 50% of HIV+ women. This was not influenced by exercise testing, habitual physical activity, or anthropometric variables. CONCLUSIONS: Given the lack of change in CRF observed in the HIV+ group after LV-HIIT intervention, it is important to focus on variations that may occur within groups.

Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy.

BACKGROUND: Direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection. METHODS: We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S. RESULTS: Mean baseline plasma HCV ribonucleic acid (RNA) = 6.7 log10 IU/mL and changed by -4.1 log10 IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean %HCV-infected cells = 25.2% (95% confidence interval [CI], 7.4%-42.9%), correlating with plasma HCV RNA (Spearman rank correlation r = 0.9); at biopsy 2 (Day 7 in 4 of 5 participants), mean %HCV-infected cells = 1.0% (95% CI, 0.2%-1.7%) (P < .05 for change), and DAAs were detectable in liver. Plasma C-X-C motif chemokine 10 (CXCL10) concentrations changed by mean = -160 pg/mL per day at 24 hours, but no further after Day 4. CONCLUSIONS: We conclude that HCV infection is rapidly cleared from liver with DAA leaving <2% HCV-infected hepatocytes at Day 7. We extrapolate that HCV eradication could occur in these participants by 63 days, although immune activation might persist. Single-cell longitudinal estimates of HCV clearance from liver have never been reported previously and could be applied to estimating the minimum treatment duration required for HCV infection.

Comorbidities in a sample of adults with HIV in Puerto Rico: an exploratory study.

BACKGROUND: Puerto Rico is among the areas with the highest estimated rates of people living with HIV in the United States. Despite the epidemiologic data available, there is limited real-world information that can help understand the comorbidities of people with HIV. In this study, we describe common comorbidities among adults with HIV attending treatment clinics in Puerto Rico. METHODS: An exploratory, retrospective, cross-sectional study was conducted at five HIV clinics in Puerto Rico. A random sample of medical records was reviewed. Descriptive statistics were used to summarize patient demographics, morbidity, and clinical characteristics. Multivariate analyses were conducted to explore comorbidities by age and sex. RESULTS: A total of 250 (179 men; 71 women) medical records were reviewed. Participants' mean age was 47.9 years and on average they had been living with HIV for 9 years. Most (97.6%) had at least one comorbidity. The most common comorbidities were dyslipidemia and hypertension. Men were more likely to have been diagnosed with alcohol misuse while women were more likely to have been diagnosed with obesity, human papillomavirus (HPV), hypothyroidism, and osteoporosis. Participants younger than 50 years of age were more likely to have history of alcohol misuse while older individuals (50 years and old) were more likely to have been diagnosed with dyslipidemia, hypertension, and diabetes. Adjusting by sex and age, women were more likely to have been diagnosed with obesity and depression and those older than 50 years were more likely to have had a diagnosis of dyslipidemia, hypertension, HPV, and diabetes. CONCLUSIONS: This is one of the few studies assessing comorbidities among adults with HIV in Puerto Rico, among Latino/Hispanics within the United States, and Latin America. Consistent with other studies, cardiovascular diseases are common among adults with HIV in Puerto Rico. Findings support the need for awareness and real-world evidence about comorbidities among people with HIV when implementing screenings and prescribing drugs.

When "the Cure" Is the Risk: Understanding How Substance Use Affects HIV and HCV in a Layered Risk Environment in San Juan, Puerto Rico.

BACKGROUND: Substance use, particularly injection drug use, continues to fuel the HIV/HCV (hepatitis C virus) epidemics in San Juan, Puerto Rico (PR). AIM: This article examines individual and sociostructural factors that affect HIV/HCV risk among people who use drugs (PWUD) living with or at risk for HIV/HCV in San Juan, PR. Findings were used to inform a community-level intervention to enhance HIV care access and retention for this population. METHOD: A rapid ethnographic assessment in collaboration with a community-based organization was conducted. Data collection took place between June and December 2013 and included field observations, 49 unstructured interviews with PWUD, and 19 key informant interviews with community stakeholders. Fieldnotes, photographs, and interview transcripts were analyzed for recurrent themes and to address the intervention-planning needs. Study results are presented as fieldnote excerpts, direct quotes from interviews, and photographs. RESULTS: Findings suggest that PWUD in PR face myriad challenges that affect HIV/HCV risk and hinder linkage to and retention in care. Results describe a layered risk environment where PWUD encounter many barriers to prevention, care, and treatment such as transience, social isolation, stigma, limited housing options, and inadequate medical and substance use disorder treatment services. DISCUSSION: These observed circumstances provide an empirical basis for the development and evaluation of comprehensive interventions that may serve to reduce barriers to care and link individuals to other supportive services. CONCLUSION: New approaches and comprehensive interventions are needed to break the structures that perpetuate risk and lack of engagement and retention in HIV care and substance use disorder treatment in San Juan.

Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults.

In a double-blind, phase 3 trial, 663 HIV-infected, virologically suppressed adults were randomized to switch to tenofovir alafenamide (TAF; n = 333) vs. remain on tenofovir disoproxil fumarate (TDF; n = 330), each coformulated with emtricitabine (FTC), while continuing their third agent (boosted protease inhibitor or unboosted third agent). At week 96, 88.6% on FTC/TAF and 89.1% on FTC/TDF had HIV-1 RNA <50 copies per milliliter [adjusted difference -0.5% (95% confidence interval: -5.3 to 4.4%)]. Proteinuria, albuminuria, proximal renal tubular function, and bone mineral density improved after switching to TAF- from TDF-containing regimens. These longer-term data support FTC/TAF as a safe, well-tolerated, and durable nucleotide reverse transcriptase inhibitor backbone.

The structural and health policy environment for delivering integrated HIV and substance use disorder treatments in Puerto Rico.

BACKGROUND: HIV prevalence in Puerto Rico is nearly twice that of the mainland United States, a level that was substantially fueled by injection drug use. Puerto Rico has a longstanding history of health provision by the public sector that directly affects how HIV and substance use disorder (SUD) treatment services are provided and funded. As part of pre-implementation research for a randomized trial of a community-level intervention to enhance HIV care access for substance users in San Juan, Puerto Rico, we sought to understand the structural and health policy environment for providing HIV and SUD treatments. METHODS: We conducted semi-structured qualitative interviews (n = 8) with government and program administrators in English and Spanish. Data were analyzed to identify dominant and recurrent themes. RESULTS: Participants discussed how lack of integration among medical and mental health service providers, lack of public transportation, and turnover in appointed government officials were barriers to integrated HIV and SUD treatment. Federal funding for support services for HIV patients was a facilitator. The Affordable Care Act has limited impact in Puerto Rico because provisions related to health insurance reform do not apply to U.S. territories. DISCUSSION AND CONCLUSIONS: Implications for intervention design include the need to provide care coordination for services from multiple providers, who are often physically separated and working in different reimbursement systems, and the potential for mobile and patient transportation services to bridge these gaps. Continuous interaction with political leaders is needed to maintain current facilitators. These findings are relevant as the current economic crisis in Puerto Rico affects funding, and may be relevant for other settings with substance use-driven epidemics.

Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1.

BACKGROUND: Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need. METHODS: We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 virologic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events. CONCLUSIONS: Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.).

Metabolic syndrome in relation to cardiorespiratory fitness, active and sedentary behavior in HIV+ Hispanics with and without lipodystrophy.

OBJECTIVE: Hispanics in Puerto Rico (PR) have a high prevalence of metabolic syndrome (met-syn), partially explained by low physical activity (PA) and possibly low cardiorespiratory fitness (VO2peak). Met-syn is also associated with lipodystrophy in HIV infected (HIV+) adults taking antiretroviral therapies. However, associations between met-syn, VO2peak, PA, sedentary behavior and lipodystrophy among HIV+ Hispanics have not been adequately reported. We tested the following hypotheses: 1) HIV+ Hispanics with lipodystrophy (HIV-Lipo) would have a higher prevalence of met-syn, lower VO2peak and PA, and higher sedentary behavior compared with those without lipodystrophy (HIV-no-Lipo) and without HIV infection (Non-HIV); and 2) met-syn would be inversely associated with VO2peak and PA, and directly associated with sedentary behavior. METHODS: Ninety Hispanic adults (32 HIV-Lipo, 28 HIV-no-Lipo, 30 Non-HIV) completed measurements of VO2,peak, anthropometry, PA and sedentary behavior with accelerometry, blood pressure, fasting glucose, insulin, and lipids. ANOVA and chi-square tests were used to detect differences between groups, and regression analyses to test associations between variables. RESULTS: More HIV-Lipo (69%) had met-syn compared with HIV-no-Lipo (39%) and Non-HIV (37%) (P = 0.002). Sedentary behavior and PA were not different, but VO2peak differed between all groups: lowest in HIV-Lipo and highest in non-HIV. PA and sedentary behavior were not associated with met-syn, but PA was directly associated with VO2peak (R2 = 0.26, p < 0.01). Also, a lower odds ratio for met-syn was observed with higher VO2peak (0.87; 95% CI: 0.83-0.95). CONCLUSION: Met-syn is related to lipodystrophy in HIV+ Hispanics in PR, and high VO2peak may protect against met-syn in this population.

Prevalence of cardiometabolic risk factors in Hispanics living with HIV.

OBJECTIVE: Human immunodeficiency virus (HIV) infection and antiretroviral treatment are associated with metabolic and cardiovascular complications that resemble metabolic syndrome (MetS) and potentially increase the risk of diabetes and cardiovascular disease in this population. The purpose of this study was to determine the prevalence of MetS and its individual components among Hispanics living with HIV in Puerto Rico. METHODS: Data from 909 clinical records were extracted and the prevalence of MetS determined using the NCEP-ATPIII criteria. Fisher's exact test was used to detect sex differences, and logistic regression to examine the effect of age, sex, smoking, years of HIV infection, antiretroviral therapy, and Hepatitis C coinfection. RESULTS: The prevalence of MetS in our study group (35.4%) was higher than previously reported in the United States, but not higher than in the general population in Puerto Rico. Females had a higher prevalence of MetS (44.2%) than males (30.5%); mostly explained by high body mass index and waist circumference. Age and sex were associated with the presence of MetS. CONCLUSION: Understanding ethnic and sex differences in the prevalence of metabolic risk factors is essential for the implementation of specific targeted interventions to prevent subsequent vascular morbidity and mortality in this population.

A randomized, partially blinded phase 2 trial of antiretroviral therapy, HIV-specific immunizations, and interleukin-2 cycles to promote efficient control of viral replication (ACTG A5024).

Strategies to limit life-long dependence on antiretroviral therapy (ART) are needed. We randomized 81 human immunodeficiency virus (HIV)-infected subjects to 4 interventional arms involving continued ART plus ALVAC vCP1452 (or placebo) with or without interleukin (IL)-2 infusions. Viral load rebound 12 weeks after ART interruption was then analyzed to assess immune control. Fifty-two subjects reached the study end point. ALVAC recipients had 0.5 log(10) lower virologic rebounds (P=.033). IL-2 plus vaccine boosted CD4(+) T cell counts (P<.001) but did not diminish viral rebound. Significant changes were not detected for HIV-specific lymphoproliferative responses in any arm. This exploratory protocol provides useful clinical data for future therapeutic immunization trial design.

Physical and leisure activity, body composition, and life satisfaction in HIV-positive Hispanics in Puerto Rico.

Hispanics represent 13% of the U.S. population but account for 19% of the new AIDS cases reported in 2000. The antiretroviral drug therapy used for the treatment of HIV/AIDS may cause lipodystrophy and insulin resistance, among other effects. Physical and leisure activities reduce these effects and improve the emotional and physical well-being of HIV-positive persons. This study describes physical and leisure activities, life satisfaction, depression, and body composition of HIV-positive Hispanics in Puerto Rico and compares body composition, CD4 counts, depression, leisure time, and life satisfaction of participants classified as physically active or inactive. Sixty-eight individuals were evaluated using questionnaires and biophysical measurements. Descriptive statistics and independent t tests were used for data analysis. Physically active participants had higher life satisfaction scores and healthier body composition as compared to those physically inactive. Health professionals must encourage the promotion of a physically active lifestyle among HIV-positive Hispanics.