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

Experience in clinical practice, these landmark clinical trials, and several cohort studies served as the basis of the changes in the new HSS guidelines that endorse ART for all HIV-infected persons. The World Health Organization (WHO) has recently published similar guidelines. ¹⁰ It is yet to be determined whether the guidelines have been implemented successfully. Nonetheless, for both the clinician and the patient where access to ongoing care and ART are available, the new guidelines greatly simplify the treatment choices.

What's New in the Guidelines?

The Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents presents significant changes in several of the tables that are most clinically useful, including Tables 6, 7, and 8. ¹ Table 6 presents recommended, alternative, and other antiretroviral regimen options. The guidelines also added new tables describing antiretroviral regimen considerations for initial therapy and the mechanisms of antiretroviral-associated drug interactions.

Initial Combination Regimens for the Antiretroviral-Naïve Patient

Five regimens are now recommended for ART-naïve patients: 4 are integrase strand transfer inhibitor-based regimens, and 1 is a ritonavir-boosted PI-based regimen (Table 1). A nonnucleoside reverse transcriptase inhibitor-based regimen is no longer recommended. The guidelines include regimens that are now considered less favorable for a variety of reasons, including reduced virologic activity and greater risk of toxicities, higher pill burden, and more potential drug interactions. Several regimens that have been widely used are now included in this latter option, in particular efavirenz plus abacavir/lamivudine (3TC), lopinavir/ritonavir plus abacavir (ABC)/3TC, and tenofovir fumarate (TDF)/emtricitabine (FTC).

The most significant change in the guideline is the reclassification of efavirenz from a recommended to an alternative therapy. The principal reasons for this change are central nervous system (CNS) AEs, which can include depression and a reported 2-fold increase in the risk of suicide or suicidal ideation. ¹¹

In November 2015, the FDA approved Genvoya, a once-daily, fixed-dose combination tablet containing elvitegravir, cobicistat, FTC, and tenofovir alafenamide (TAF). ¹² With this approval, there are now 5 once-daily HIV treatment options. This new drug is similar to elvitegravir/cobicistat/TDF/FTC, but it substitutes TAF for TDF. The benefits of this substitution include less bone loss and decreased renal toxicity. ^13-15 Genvoya may be prescribed in patients with a 30 mL/min creatinine clearance. The TAF-containing once-daily formulation achieves higher intracellular levels and lower blood levels of TAF. Therefore, the cholesterol-lowering benefits are less than those of the TDF-containing alternative.

In the 2015 guidelines, Table 7 provides concise guidance on the selection of an ART regimen based on patient and regimen characteristics, including food-based AEs; the presence of other medical and/or psychiatric conditions; and the presence of co-infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), and tuberculosis. ¹ In addition, Table 8 outlines the advantages and disadvantages of the different classes of ART. ¹ For example, dolutegravir may have a higher barrier to resistance than that of elvitegravir or raltegravir. ¹⁶ It is now possible for those living with HIV to have ongoing viral suppression, which will not only improve their lives, but also decrease the risk of HIV transmission to sexual partners. Starting from the time of diagnosis, achieving viral suppression is dependent on a link to care with initiation of ART and retention in care. The 5 once-daily options should improve adherence. The infrastructure to ensure lifelong retention in care, medication availability, and adherence still poses many challenges.