Treatment Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents: An Update

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.

Drug Interactions

Given the availability of numerous once-daily ART regimens, prescribing ART has been greatly simplified. Nonetheless, there are many pharmacokinetic drug-drug interactions between antiretroviral drugs and concomitant medications. When changing either the ART or adding or changing other medications, the clinician must always pay attention to potential drug-drug interactions. Consideration must be given to the interaction with drugs that affect antiretroviral absorption—particularly, acid-reducing agents and products that contain polyvalent cations, including calcium and magnesium.

When antiretrovirals that undergo hepatic metabolism are given with other drugs that also are metabolized by the cytochrome P450 enzyme system or other hepatic enzymes, the levels of antiretrovirals or other drug may be significantly increased or decreased.¹ The 2 booster—cobicistat and ritonavir—used to increase certain antiretrovirals levels also may alter the metabolism of other drugs.^28,29 The new guidelines contain updated and detailed tables on drug-drug interactions. Given the comorbid conditions, particularly among those aging with HIV, polypharmacy is an increasingly common concern. It is essential for clinicians to work with knowledgeable HIV pharmacists to ensure the correct and safe prescribing of all medications.