Dr. Gibert is chair of the institutional review board and director of special projects at the Washington DC VAMC and professor of medicine at the George Washington University School of Medicine and Public Health in Washington, DC.
Author disclosures The author reports no actual or potential conflicts of interest with regard to this article.
Disclaimer The opinions expressed herein are those of the author and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
References
Treatment-Experienced Patients
The guidelines were updated to include more direction on virologic failure to a first-line regimen as well as a second-line regimen failure or beyond. It includes a discussion of treatment options for achieving full virologic suppression. There also are treatment recommendations for patients with multidrug viral resistance in whom maximal viral suppression may not be achieved. For such patients, ART should be continued to preserve immunologic function, lessen clinical progression, and minimize resistance to drug classes that could include new efficacious drugs. 17,18
There is also a discussion in the guidelines of the issues surrounding isolated CNS virologic failure and the onset of new neurologic symptoms. With CNS virologic failure, magnetic resonance brain imaging may be abnormal with a lymphocytic pleocytosis in the cerebrospinal fluid (CSF). If available to guide therapy, CSF HIV RNA should be measured, and HIV drug resistance in the CSF should be tested. Central nervous system viral escape should be differentiated from other CNS conditions, such as herpes zoster infection; incidental mild CSF HIV RNA increases; or the now relatively common but chronic neurocognitive impairment seen with HIV infection. 19,20
Poor CD4+ Recovery and Persistent Inflammation Despite Viral Suppression
For patients on ART who achieve viral suppression but fail to have a significant increase in CD4+ cell count over time (particularly for the patient with a CD4+ cell count < 200 cells/mm3), the guidelines do not endorse additional ARTs or switching the regimen. However, there may be an increased risk of non-AIDS mortality and morbidity, including cardiovascular disease. For such patients, interleukin-2 adjunctive therapy has no demonstrated clinical benefit. 21 Interleukin-7 and recombinant human growth hormone should be used only as part of a clinical trial.
It is now evident that immune activation and inflammation, although lessened, persist despite ART-mediated viral suppression. 22,23 There is no recommendation to monitor markers of immune activation and inflammation. Efforts should focus on risk factor modifications, such as smoking cessation, improved diet, treatment of alcohol abuse and dependence, regular exercise, and maintenance of appropriate weight. Emphasis should be on treating chronic comorbidities, such as hypertension, diabetes, osteoporosis, and hyperlipidemia.
HIV/HCV Co-infection
According to the WHO, 130 to 150 million people worldwide have chronic HCV infection. 24 In the U.S., it is estimated that up to one-quarter of HIV-infected persons have HCV co-infection. 25 With the currently available oral direct-acting agents (DAAs) for the treatment of chronic HCV infection in patients with HIV/HCV co-infection, rates of sustained virologic response to treatment are comparable in patients with HIV/HCV co-infection with those of patients with HCV monoinfection. 26 Accordingly, all HIV-infected patients should be screened for HCV infection, and HIV ART should not be deferred for most patients.
For patients with a CD4+ cell count of < 200 cells/mm3, treatment of HCV should be deferred until the patients are on a stable and effective ART regimen. Whereas for those with a CD4+ cell count > 500 cells/mm3, HCV can be treated before initiating HIV ART. When initiating HCV therapy, clinicians must pay attention to drug-drug interactions. Patients with cirrhosis are particularly at risk. The most recent guidelines for the treatment of HCV co-infection should be reviewed when selecting a DAA to treat HCV. 27 Many patients are now being treated successfully for HCV co-infection. Extending such therapy to all patients with HIV/HCV co-infection for whom treatment is appropriate should be a priority for clinicians, insurance providers, and policy makers.
