The Academy’s “Clinical Research Update” features clinical information from Carolyn Chu, MD, MSc, AAHIVS who serves as chief medical officer for the Academy. Dr. Chu provides a short synopsis of key clinical studies, reviews, and clinical practice guidelines selected on the basis of having immediate or important clinical implications for our Academy frontline members and their patients. Periodic updates from the U.S. Department of Health and Human Services (DHHS) HIV Clinical Practice Guidelines are also included.
Clinical Research Update 2.23.21 – Interventions to Improve HIV Care Continuum Outcomes Among Individuals Released from Prison or Jail
Clinical Research Update 2.9.21 – Risk of Smoking-related Cancers Among Women and Men Living With and Without HIV
Clinical Research Update 1.26.21 – Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine and the BNT162b2 mRNA Covid-19 Vaccine
Clinical Research Update 12.29.20 – NIH Workshop on HIV-Associated Comorbidities, Coinfections, and Complications: Summary and Recommendation for Future Research
Clinical Research Update 12.22.20 – Risk Factors for Weight Gain Following Switch to Integrase Inhibitor-Based Antiretroviral Therapy
Clinical Research Update 12.15.20 – Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate
Clinical Research Update 12.8.20 – COVID-19 Related Medical Mistrust, Health Impacts, and Potential Vaccine Hesitancy Among Black Americans Living with HIV
Clinical Research Update 12.1.20 – Outcomes of Coronary Artery Bypass Grafting in Patients with HIV
Clinical Research Update 11.24.20 – Evolution of Drug Interactions with Antiretroviral Medication in People with HIV
Clinical Research Update 11.17.20 – Surprisingly Low Levels of Measles Immunity in Persons With HIV: A Seroprevalence Survey in a United States HIV Clinic
Clinical Research Update 11.10.20 – Safety and Efficacy of the HIV-1 Attachment Inhibitor Prodrug Fostemsavir in Heavily Treatment-Experienced Individuals: Week 96 Results of the Phase 3 BRIGHTE Study
Clinical Research Update 11.3.20 – Virological Failure and Acquired Genotypic Resistance Associated with Contemporary Antiretroviral Treatment Regimens
Clinical Research Update 10.27.20 – Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients with HIV and Coronavirus Disease-19
Clinical Research Update 10.20.20 – ART Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the ISA–USA Panel
Clinical Research Update 10.13.20 – Structural and Functional Brain Abnormalities in HIV Disease Revealed by Multimodal MRI Fusion: Association with Cognitive Function
Clinical Research Update 10.6.20 – Frailty Is Associated with Mortality and Incident Comorbidity Among Middle-Aged HIV-Positive and HIV-Negative Participants
Clinical Research Update 9.29.20 – Screening & Enrollment by Sex in HIV Clinical Trials in the United States
Clinical Research Update 9.22.20 – Prevalence of Hepatitis A Immunity and Decision-tree analysis Among Men Who Have Sex With Men and are Living With HIV in Tokyo
Clinical Research Update 9.15.20 – Prospective International Study of Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome and Death in People Living with HIV and Severe Lymphopenia
Clinical Research Update 9.8.20 – Trends in Time from HIV Diagnosis to First Viral Suppression Following Revised U.S. HIV Treatment Guidelines, 2012–2017
Clinical Research Update 9.1.20 – Outcomes Among HIV-Positive Patients Hospitalized With COVID-19
Clinical Research Update 8.25.20 – Rapid antiretroviral therapy among individuals with acute and early HIV
Clinical Reserach Update 8.18.20 – HIV infection is associated with lower risk of hepatocellular carcinoma after sustained virological response to direct-acting antivirals in HCV infected-patients with advanced fibrosis
Clinical Research Update 8.11.20 – Deaths attributable to cancer in the United States HIV population during 2001-2015
Clinical Research Update 8.4.20 – AIDS 2020 Highlights – Part Four
Clinical Research Update 7.28.20 – AIDS 2020 Highlights – Part Three
Clinical Research Update 7.21.20 – AIDS 2020 Highlights – Part Two
Clinical Research Update 7.14.20 – AIDS 2020 Highlights – Part One
Clinical Research Update 6.30.20 – Initiation of ART in the Hospital is Associated with Linkage to HIV Care for Persons with HIV and Substance Use
Clinical Research update 6.23.20 – Integrase Strand Transfer Inhibitors are associated with lower risk of incident Cardiovascular Disease in People Living with HIV
Clinical Research Update 6.16.20 – The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men
Clinical Research Update 6.9.20 – The HIV Outpatient Study—25 Years of HIV Patient Care and Epidemiologic Research
Clinical Research Update 6.2.20 – Recurrence and Occurrence of Kaposi’s Sarcoma in Patients Living with HIV and on Antiretroviral Therapy, despite Suppressed HIV Viremia
Clinical Research Update 5.26.20 (CROI 2020) – Changes in Body Mass Index and the Risk of Cardiovascular Disease: The D:A:D Study
Clinical Research Update 5.19.20 (CROI 2020) – Trends in HIV Drug Resistance in the United States
Clinical Research Update 5.12.20 (CROI 2020) – 144-Week Efficacy and Safety of B/F/TAF in Treatment-Naive Adults ≥50 Years
Clinical Research Update 5.5.20 (CROI 2020) – Increased Overall Life Expectancy but Not Comorbidity-free Years for People with HIV
Clinical Research Update 4.28.20 (CROI 2020) – HIV Viral Blips in Adults Treated with INSTI-based Regimens through 144 weeks
Clinical Research Update 4.21.20 (CROI 2020) – Long-Acting Cabotegravir + Rilpivirine for HIV Treatment: FLAIR Week 96 Results
Clinical Research Update 4.14.20 (CROI 2020) – Safety and Efficacy of Dolutegravir vs Efavirenz and Tenofovir Disoproxil Fumarate vs Tenofovir Alafenamide in Pregnancy: IMPAACT 2010 Trial
Clinical Research Update 4.7.20 (CROI 2020) – Cabotegravir + Rilpivirine every 2 Months is Non-Inferior to Monthly: ATLAS-2M Study
Clinical Reseach Update 3.31.20 – Elvitegravir-Cobicistat-Emtricitabine-Tenofovir Alafenamide Single-tablet Regimen for HIV Postexposure Prophylaxis
Clinical Research Update 3.24.20 – Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression
Clinical Research Update 3.17.20 – The Modern Epidemic of Syphilis
Clinical Research Update 3.10.20 – Outcomes in Human Immunodeficiency Virus-Infected Recipients of Heart Transplants
Clinical Research Update 3.3.20 – Dolutegravir- based Antiretroviral Therapy for Patients Coinfected with Tuberculosis and HIV
Clinical Research Update 2.25.20 – Adherence and Viral Suppression among Participants of the Patient-centered HIV Care Model Project: A Collaboration Between Community-based Pharmacists and HIV Clinical Providers
Clinical Research Update 2.18.20 – Atherosclerotic Cardiovascular Disease Risk Profile of Tenofovir Alafenamide versus Tenofovir Disoproxil Fumarate
Clinical Research Update 2.11.20 – HIV and Hepatitis C Virus Infection Testing Among Commercially Insured Persons Who Inject Drugs
Clinical Research Update 2.4.20 – Week 96 results of a phase 3 trial of D/C/F/TAF in treatment-naïve HIV-1 patients.
Clinical Research Update 1.28.20 – Clinical and Economic Impact of Ibalizumab for People with Multidrug-Resistant HIV in the United States
Clinical Research Update 1.21.20 – Accuracy in self-report of viral suppression among HIV-positive men with HIV-negative male partners
Clinical Research Update 1.7.20 – Effect of Cannabis Use on HIV DNA during Suppressive Antiretroviral Therapy
Clinical Research Update 12.17.10 – Nonadherence to Any Prescribed Medication Due to Costs among Adults with HIV Infection
Clinical Research Update 12.10.19 – Female genital tract shedding of HIV-1 is rare in women with suppressed HIV-1 in plasma
Clinical Research Update 12.3.19 – Use of Contemporary Protease Inhibitors and Risk of Incident Chronic Kidney Disease in Persons with HIV: The D:A:D Study
Clinical Research Update 11.26.19 – Switching to Fixed-Dose Bictegravir, Emtricitabine, and Tenofovir Alafenamide (B/F/TAF) in Virologically Suppressed HIV-1 Infected Women
Clinical Research Update 11.19.19 – Effect of daily consumption of extra virgin olive oil on the lipid profile and microbiota of HIV-infected patients over 50 years of age
Clinical Research Update 11.12.19 – Changes in Body Mass Index and Atherosclerotic Disease Risk Score After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide
Clinical Research Update 11.5.19 – Noninferiority of simplified dolutegravir monotherapy compared to continued combination antiretroviral therapy that was initiated during primary HIV infection: A randomized, controlled, multisite, open-label noninferiority trial.
Clinical Research Update 10.29.19 – Lipid management for the Prevention of Atherosclerotic Heart Disease
Clinical Research Update 10.22.19 – Use of Recommended Preventive Health Care Services and Variations in HIV Care among Women with HIV in the United States
Clinical Research Update 10.8.19 – Association of Human Immunodeficiency Virus Infection and Risk of Peripheral Artery Disease
Clinical Research Update 10.1.19 – Non-AIDS comorbidity burden differs by sex, race, and insurance type in aging adults in HIV care.
Clinical Research Update 9.24.19 – Weight gain associated with Integrase Stand Transfer Inhibitor use in women
Clinical Research Update 9.17.19 – Serious clinical events in HIV-positive persons with chronic kidney disease
Clinical Research Update 9.10.19 – Update to the Varicella-Zoster Virus (VZV) Disease Section of the DHHS Adult and Adolescent Opportunistic Infections Guidelines
Clinical Research Update 9.3.19 – Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials
Clinical Research Update 8.27.19 – Increased risk of anemia, neutropenia and thrombocytopenia in people with HIV and well-controlled viral replication
Clinical Research Update 8.20.19 – Alopecia After Switch to Tenofovir Alafenamide in 6 African American Women
Clinical Research Update 8.13.19 – Low level viremia and virologic failure in persons with HIV infection treated with antiretroviral therapy
Clinical Research Update 8.6.19 – Generalized anxiety disorder symptoms among persons with diagnosed HIV in the United States
Clinical Research Update 7.30.19 – Long-term evolution of CD4+cell count in patients under combined antiretroviral therapy
Clinical Research Update 7.16.19 – Nonadherence and unsuppressed viral load across adolescence among US youth with perinatally acquired HIV
Clinical Research Update 7.9.19 – Herpes Zoster rates continue to decline in people living with HIV but remain higher than rates reported in the general US Population.
Clinical Research Update 7.2.19 – Pregnancy and Neonatal Outcomes Following Prenatal Exposure to Dolutegravir
Clinical Research Update 6.25.19 – Colorectal Cancer Screening in People With and Without HIV in an Integrated Health Care Setting
Clinical Research Update 6.18.19 – The benefit of immediate compared with deferred antiretroviral therapy on CD4+ cell count recovery in early HIV infection
Clinical Research Update 6.11.19 – Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: Week 96 results from a randomized, double-blind, multicenter, phase 3, non-inferiority trial
Clinical Research Update 5.30.19 – Clinical impact and cost-effectiveness of genotype testing at HIV diagnosis in the United States
Clinical Research Update 5.16.19 – Sexually Acquired Hepatitis C Infection in HIV-Uninfected Men Who Have Sex with Men Using Preexposure Prophylaxis Against HIV
Clinical Research Update 5.9.19 – Differences by Sex in Cardiovascular Comorbid Conditions Among Older Adults Receiving HIV
Clinical Research Update 5.2.19 – Characterizing the HIV Care Continuum among Transgender Women and Cisgender Women and Men in Clinical Care
Clinical Research Update 4.18.19 – Association of PrEP with Incidence of STIs Among High Risk Individuals
Clinical Research Update 4.11.19 – Short Physical Performance Battery (SPPB)
Clinical Research Update 4.4.19 – What’s New in the DHHS Guidelines?
Featured Literature 3/28/19
De Voux A. et al. Syphilis testing among sexually active men who have sex with men and who are receiving care in the United States: Medical Monitoring Project, 2013-2014. Clin Infect Dis, March 2019; 68:934-939.
Current guidelines from the CDC recommend yearly screening for syphilis in sexually active MSM including those with HIV. More frequent testing is recommended for MSM at high-risk or if clinically indicated. This study analyzed the most recent data from the Medical Monitoring Project – a surveillance system that includes cross-sectional estimates of clinical and behavioral characteristics of HIV-positive adults receiving medical care in the U.S. Data was abstracted from patient medical records looking specifically at the prevalence of syphilis testing in MSM by an HIV provider in the past 3, 6, or 12 months. The majority of subjects were >30 years and 86% identified as homosexual. Almost 50% reported condomless sex in the past 12 months and 58% reported multiple sex partners. Only 71% of all sexually active MSM had at least one syphilis test in the past 12 months. The numbers were slightly higher (75%) for men reporting condomless sex (75%) and for those reporting >two sex partners (77%). The prevalence of syphilis testing was only 43% in the past six months and 22% in the past three months in men reporting condomless sex. Being that almost one-third of sexually active MSM were not tested for syphilis in the past year, the authors conclude that this lack of screening represents missed opportunities to diagnose and treat this common STI and decrease the risk of HIV transmission as well.
Commentary: The low rate of screening is disconcerting as rates of syphilis (30,644 cases reported in 2017) and other STDs in the U.S. continue to increase. Greater efforts to improve syphilis screening, especially for high-risk patients are unquestionably needed.
Featured Literature 3/21/19
High virologic suppression rates with immediate antiretroviral therapy initiation in a vulnerable urban clinic population.
Coffey, S et al. AIDS: April 1, 2019 – Volume 33(5):825–32
There has been a progressive move to encourage providers to start ART as soon as possible following a new HIV diagnosis. This study from theRAPIDprogram (Rapid ART for Individuals with HIV Diagnosis) in San Francisco included patients directly referred from testing sites for same or next-day intake visits. All received multidisciplinary evaluations and insurance enrollment/optimization. Patients were provided ART starter packs with close follow-up. Of the 225 patients referred to RAPID from 2013 to 2017, 96% were started on immediate-ART. More than 50% had a substance use disorder, 48% had a mental health diagnoses and 31% had unstable housing. Baseline median CD4+ cell count 441 and viral load was 37,000 copies. At one year after intake, 96% achieved viral suppression. Over a median follow-up time of 1.09 years (range of 0-3.92), 15% had viral rebound, but most (78%) re-suppressed. Viral suppression rates were 92% at last recorded viral load. The study concludes that in an urban clinic caring for patients with high rates of mental illness, substance use and housing instability, immediate ART is feasible, acceptable, and can be successfully implemented with adequate staffing and support.
Commentary: Same-day treatment has proven successful in various settings. Although immediate ART is discussed in the DHHS guidelines, it is not part of their current recommendations. This strategy is recommended by the WHO guidelines. Immediate treatment may not be clinically necessary for patients with less intensive needs but certainly should be started as early as possible.
Sakabumi, DZ. Chronic Distal Sensory Polyneuropathy Is a Major Contributor to Balance Disturbances in Persons Living With HIV Journal of Acquired Immune Deficiency Syndromes: 2019;80(5):568–573.
Medical comorbidities are common in older persons living with HIV (PLWH). Chronic distal sensory polyneuropathy(cDSPN), historically associated with peripheral nerve damage from advanced HIV disease or antiretroviral therapy-particularly dideoxynucleosides may contribute to balance difficulties and falls. The contribution of neuropathy has not been well-studied in the post-ART era. This study included 3,379 PLWH and HIV-negative adults. All participants underwent a thorough neurologic examination to document objective findings of cDSPN including pain, numbness, or pain. They also were asked specific questions regarding balance disturbance over the past 10 years that were classified as “mild to moderate”, “minimal” or “none”. Other variable assessed were age, HIV status, treatment characteristics and current medications including sedatives and opioids. Fifty-two percent of the subject met criteria for cDSPN. Balance problems were more common in those with cDSPN. Eleven percent reported balance disturbances with the rate in PLWH exceeding that of HIV-negative persons [odds ratio 2.6] with older participants more likely to report balance disturbances than younger ones. Adjusting for relevant covariates, disturbances attributable to cDSPN were much more frequent among HIV+ adults. Among individuals with cDSPN, the authors conclude that this condition contributes to balance problems in PLWH. Office based assessment for sensory neuropathy in older PLWH should be a clinical priority. It can identify those at risk for falls and subsequent consequences – including fractures, intracranial injuries, hospitalization, and death.
Commentary: In the post-ART era, peripheral neuropathies are rarely discussed or assessed for clinically. The prevalence is this study was > 50%. This remains yet another co-morbidity in our aging HIV population that should be considered and evaluated diagnostically by EMG and nerve conduction studies if indicated.
Althoff KN. Contributions of traditional and HIV-related risk factors on non-AIDS-defining cancer, myocardial infarction, and end-stage liver and renal diseases in adults with HIV in the USA and Canada: a collaboration of cohort studies. Lancet HIV 2019;6(2) PE93-E104.This study included patients from NA-ACCORD (US and Canada) who were in care from 2000 to 2014. The goal was to estimate population attributable factors (PAFs) of modifiable or preventable HIV-related and traditional risk factors for AIDS-defining cancers, Myocardial infarction (MI), end-stage liver disease, and end-stage renal disease. Traditional risk factors were addressed including smoking, hypertension, diabetes, hyperlipidemia, and stage 4 kidney disease. HIV risk factors included history of AIDS, CD4 count < 200, and detectable viremia (HIV-RNA > 400). The authors determined that smoking cessation would have avoided 24% of non-AIDS cancers and 37% of heart attacks. Treating hypertension and elevated cholesterol would have prevented between 44% and 42% of MIs. Similar benefits were seen for treating hypertension (39 % reduction in renal disease). Treatment of chronic HCV had the greatest PAF in preventing liver disease.
Commentary: Although not surprising, these data can be useful in screening, counseling, and treating patients regarding co-morbid conditions and risk factors for cancer, heart disease as well as kidney and liver disease. As with other studies, smoking cessation has a significant impact on reducing disease incidence in PLWH.
Cessation of cigarette smoking and the impact on cancer incidence in HIV-infected persons: The data collection on adverse events of Anti-HIV Drugs Study. Clin Infect Dis 15 February 2019;68(4)650-656.
Cancers continue to be a major source of morbidity and mortality in persons living with HIV. The reasons are likely multifactorial and include chronic immune suppression and inflammation, longer life-expectancy but also lifestyle-related factors. This study from the D:A:D cohort included 35,442 patients who contributed 310,000-person years of follow-up. At baseline, 49% were active smokers and 21% were ex-smokers. The incidence of all cancers in this group was 2,183 and was highest in the first year after patients stopped smoking. There were 271 cases of lung cancer and the risk for this malignancy, although greatest in year one of smoking cessation, remained 8-fold higher even at five years after smoking cessation. For other cancers related to smoking (head and neck, esophageal, gastric, GU, colon, rectal, ovarian and cervical), incidence declined after one year of not smoking to a level similar to that in non-smokers.
Commentary: The D:A:D cohort continues to provide valuable observational data regarding co-morbidities in PLWH. Despite this discouraging data related to lung cancer, smoking cessation should remain a priority in caring for these individuals.
Eron J et al. Safety of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-1 infected adults with end-stage renal disease on chronic hemodialysis: an open-label, single-arm, multicenter phase 3 trial. Lancet HIV 2019,6(1): PE15-E24.
This was open-label, single-arm, that included 55 patients with ESRD (creatinine clearance <15 mL/min), on chronic hemodialysis (HD). All had viral suppression (HIV-1 RNA <50 copies per mL) and a CD4 count of at least 200 while on a stable ART for at least 6 months. Patients were switched to co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (Genvoya) daily after HD. The primary endpoint was the incidence of treatment-emergent adverse events > grade 3 up to week 48. Thirty-three percent experienced an AE but none were felt to be treatment-related and only 3 stopped ART. At 48 weeks, switching to the single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide was well tolerated. 82% maintained HIV-RNA levels of < 50 copies. This study will continue for at least 96 weeks.
Commentary: Although not recommended by the current DHHS guidelines, this STR may be a reasonable option for patients with HIV on HD who are often on multiple medications and thus lessen pill burden. Per the original study design, these patients will be followed for 96 weeks so more data regarding efficacy and safety should be forthcoming.
Prophylaxis for disseminated Mycobacterium avium Complex Disease (MAC) no longer recommended by DHHS Guidelines. Included in the most recent update from the DHHS is a new recommendation the primary prophylaxis against disseminated MAC disease is NOT recommended for adults and adolescents with HIV who immediately initiate ART. Primary MAC prophylaxis, if previously initiated, should be discontinued in adults and adolescents who are on a fully suppressive ART regimen. Patients who are not receiving ART or who remain viremic on ART and have no current options for a fully suppressive ART regimen should receive chemoprophylaxis against disseminated MAC if they have CD4 counts <50 cells/mm3. These new recommendations are based on two randomized, placebo-controlled trials and observational data which found that persons with HIV taking ART could discontinue primary prophylaxis with minimal risk of developing MAC disease. These recommendations are now consistent with the IAS-USA guidelines published in July 2018.