The human immunodeficiency virus (HIV) is constantly changing, and because medications are being improved, the recommendations for the best ways to treat HIV are being updated regularly.
In April 2015, the US Department of Health & Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents, which works through the Office of AIDS Research Advisory Council, published updated guidelines to include the latest data and research.1 New medications launched in the past year are now included in the guidelines, along with updates regarding which regimens are best for the treatment of HIV infection in adults and adolescents in the United States.
Understanding Regimen Ratings
The panel, which consists of 40 voting members with expertise in HIV care and research, based the recommendations in these guidelines on studies published in peer-reviewed journals. However, they noted that on some occasions when new information may affect patient safety, the panel may include unpublished data as evidence to revise the guidelines. Data were rated based on the strength of the recommendation (A, strong; B, moderate; C, optional) and quality of the evidence to support the recommendation (I, ≥1 randomized controlled trials with clinical outcomes and/or validated laboratory end points; II, ≥1 well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; and III, expert opinion).
This year there are 5 recommended regimens with A-I ratings, 6 alternative regimens with BI-III ratings, and 7 other regimens with CI-III ratings. Integrase strand transfer inhibitors (INSTIs) dominate the recommended regimens, along with 1 protease inhibitor–based regimen (Table).1 In addition, the INSTIs have been effective in controlling viral loads with limited toxicity and a minimal amount of drug–drug interactions, according to the panel. The protease inhibitor regimen is less likely than other regimens to lead to drug resistance in this patient population and is used for patients with variable or questionable medication adherence. Two regimens previously classified as recommended are now categorized as alternative.
Key Changes in Regimen Recommendations
- Combination therapy with atazanavir and ritonavir was previously recommended as treatment and is now classified as an alternative regimen based on data from a recent study by Lennox and colleagues for the AIDS Clinical Trials Group A5257 team. The results of the study demonstrated that ritonavir-boosted atazanavir plus tenofir/emtricitabine had higher rates of discontinuation because of toxicity.2
- Similarly, the updated guidelines now classify Atripla (efavirenz, tenofovir disoproxil fumarate, and emtricitabine) as an alternative regimen. The drug has been getting increased attention from clinicians and those conducting clinical trials because of the increased risk for suicide and central nervous system adverse events associated with taking efavirenz.3 Because of this safety issue, Atripla was removed from the preferred regimen grouping.
- The recommendation to use 2 nucleoside reverse transcriptase inhibitors (NRTIs) as the backbone of all therapies whenever possible has not changed. Likewise, the need for human leukocyte antigen (HLA) testing prior to abacavir use, and the creatinine clearance recommendations regarding tenofovir disoproxil fumarate use, remain the same.
- Regimens with caveats based on viral load and CD4+ T-cell count were moved to the alternative or other categories, with that same requirement. These medications are less efficacious if the patient’s CD4 levels do not meet the specified criteria, and would have less benefit.
- The 2 regimens with <2 NRTIs are now listed in the other category, and would only be appropriate for use in patients who are unable to use abacavir or tenofovir disoproxil fumarate.1
New Antiretroviral Medications
Three new antiretroviral medications recently entered the market. The first is a once-daily, single-tablet, combination product called Triumeq.4 Triumeq was approved in August 2014, and contains dolutegravir, an INSTI, with a backbone of abacavir and lamivudine to complete the full regimen. Based on experience and research on the topic, there seems to be a push for once-daily, single-tablet, full regimens to increase patient adherence and improve outcomes. Limitations for these products include the inability to adjust for specific patient characteristics (eg, poor kidney function or HLA type). In January 2015, 2 medications with the pharmacokinetic booster cobicistat as a part of their formulation were introduced.5-8 Atazanavir and darunavir are now available as combination products containing cobicistat, thus decreasing some of the pill burden and increasing the effects of these protease inhibitors.
The future of HIV antiretrovirals may be shifting from creating new medications to improving those currently available through boosting and combining. Hopefully these innovations, along with the panel’s guideline updates, will help lower the pill burden and improve patient adherence and outcomes.
- US Department of Health & Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Updated April 8, 2015. Accessed August 10, 2015.
- Lennox JL, Landovitz RJ, Ribaudo HJ, et al. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014;161:461-471.
- Mollan KR, Smurzynski M, Eron JJ, et al. Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data. Ann Intern Med. 2014;161:1-10.
- Page MR. Triumeq by ViiV Healthcare. Specialty Pharmacy Times. April 15, 2015. www.specialtypharmacytimes.com/publications/specialty-pharmacy-times/2015/april-2015/Triumeq-by-ViiV-Healthcare. Accessed August 10, 2015.
- US Department of Health & Human Services. Darunavir/Cobicistat. https://aidsinfo.nih.gov/drugs/538/prezcobix/0/professional. Updated February 16, 2015. Accessed August 10, 2015.
- US Department of Health & Human Services. Atazanavir/Cobicistat. https://aidsinfo.nih.gov/drugs/537/evotaz/0/professional. Updated February 13, 2015. Accessed August 10, 2015.
- US Food and Drug Administration. Evotaz. www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=206353&DrugName=EVOTAZ&ActiveIngred=ATAZANAVIR%2SULFATE%3B%20COBICISTAT&SponsorApplicant=BRISTOL%2MYERS%20SQUIBB&ProductMktStatus=1&goto=Search.DrugDetails. Accessed August 10, 2015.
- US Food and Drug Administration. Prezcobix. www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=205395&DrugName=PREZCOBIX&ActiveIngred=COBICISTAT%3B%2DARUNAVIR%20ETHANOLATE&SponsorApplicant=JANSSEN%20PRODS&ProductMktStatus=1&goto=Search.DrugDetails. Accessed August 10, 2015.