CLINICAL RESEARCH UPDATE


AAHIVM’s “Clinical Research Update” features clinical information from Jeffrey T. Kirchner, DO, AAHIVS who serves as chief medical officer for the Academy. Dr. Kirchner 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 AAHIVM front-line 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 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 5.23.19 – Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy

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.

Featured Literature:
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.

Featured Literature: 
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.

Featured Literature:
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.

Featured Literature:
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.

Learn more: https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-opportunistic-infection/0