CLINICAL CORNER

AAHIVM’s “Clinical Corner” 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.

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