IAS-USA releases recommendations for treatment, prevention of HIV with antiretroviral drugs

The International Antiviral Society-USA Panel has released updated guidelines for using antiretroviral drugs in adults with HIV, and for using antiretroviral agents for HIV prevention.

The recommendations, published in JAMA, are an update from 2014, due to "substantial advances in the use of antiretroviral drugs (ARVs)," Huldrych F. Günthard, MD, from the division of infectious diseases and hospital epidemiology at University Hospital Zurich, and colleagues said.

"The revision of these recommendations discusses the latest developments in uses of ARVs, summarizing current knowledge on the following: When to start therapy, including optimal initial treatment regimens; [antiretroviral therapy (ART)] for patients with opportunistic infections (OIs); when and how to switch ART; laboratory monitoring; engagement in care and ART adherence; and prevention of HIV infection," they wrote.

The authors assembled a panel of HIV experts to assess data from peer-reviewed journals, conference abstracts and regulatory agencies. Each recommendation was graded on both the quality and strength of available evidence.

The panel issued a strong recommendation with high quality evidence that ART be used for all patients infected with HIV with detectable viremia, regardless of CD4 cell count. They recommended several optimal regimens, which consist of two nucleoside reverse transcriptase inhibitors (NRTIs) and an integrase strand transfer inhibitor (InSTI). The following regimens received strong recommendations with high quality evidence: Triumeq (dolutegravir/abacavir/lamivudine, Viiv Healthcare); Tivicay (dolutegravir, Viiv Healthcare) plus Descovy (tenofovir alafenamide[TAF]/emtricitabine, Gilead Sciences); and Genvoya (elvitegravir/cobicistat/TAF/emtricitabine, Gilead Sciences).

They reported that other regimens, such as nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with two NRTIs, are also effective.

There was strong, high-quality evidence for pregnant women with HIV to initiate ART for their health and to reduce HIV transmission, and for patients with hepatitis B with HIV to initiate ART with tenofovir disoproxil fumarate (TDF) or TAF, lamivudine or emtricitabine and another component.

The panel issued other recommendations for special populations, such as using entecavir for patients who have hepatitis B; ensuring that patients with hepatitis C and HIV utilize ART regimens that don't interact with other therapies; not using TDF for patients with osteoporosis or osteopenia; and monitoring patients with kidney disease when ART is initiated or changed.

As detailed in the guidelines, some patients who achieved virologic suppression with older regimens may benefit from switching to a single-pill regimen, such as dolutegravir/abacavir/lamivudine, elvitegravir/cobicistat/emtricitabine/TAF, Stribild (elvitegravir/cobicistat/emtricitabine/TDF, Gilead Sciences) or Complera (rilpivirine/emtricitabine/TDF, Gilead Sciences). Some scenarios in which patients may want to switch include food restrictions, adverse effects, drug interactions, pregnancy or drug toxicities.

The panel also stressed the importance of improving care access and retention.

"Achieving the full benefits of treatment and prevention afforded by ART requires early diagnosis, rapid linkage to care, continuous retention in care, and uninterrupted access and adherence to ART," Günthard and colleagues said. "Late diagnosis and presentation for HIV care and global challenges that have improved only modestly over decades. To avoid missed opportunities for earlier diagnosis, routine opt-out HIV screening is recommended in primary medical care settings and emergency departments and for all pregnant women."

They suggested various approaches, including brief case management after HIV diagnosis and phone and text reminders before appointments and after missed appointments, which both had strong and high-quality evidence.

Finally, the researchers issued strong, high-quality evidence-based recommendations for daily Truvada (tenofovir disoproxil fumarate/emticitabine, Gilead Sciences) as preexposure prophylaxis (PrEP) to prevent HIV infections in high-risk individuals, such as those "from a population with an HIV incidence of at least 2% per year of HIV-infected persons who do not have viral suppression."

"Antiretroviral agents remain the cornerstone of HIV treatment and prevention," Günthard and colleagues concluded. "All HIV-infected individuals with detectable plasma virus should receive treatment, with recommended initial regimens consisting of an InSTI plus two NTRIs. PrEP should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults."

In an accompanying editorial, Kenneth H. Mayer, MD, and Douglas S. Krakower, MD, both affiliated with The Fenway Institute, Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, wrote that the guidelines represent many successes, but there are still challenges ahead.

"The current IAS-USA guidelines reflect the hard-won success of 35 years of clinical research," they wrote. "Although challenges remain to optimize the cascade of care and to prevent new infections, and an aging epidemic will present new challenges, these concerns reflect the successes of highly effective antiretroviral therapy."

Mayer and Krakower concluded: "Historians may wonder whether the pace of discovery in the early days of the epidemic could have been accelerated, but no one can doubt the signal accomplishments of biobehavioral research and community engagement in forging a common strategy to deal with this global pandemic, one that continues to pose new challenges. – by Chelsea Frajerman Pardes

Disclosures: Günthard reports receipt of grants from the Swiss National Science Foundation, Swiss HIV Cohort Study, University of Zurich, Yvonne Jacob Foundation, and Gilead Sciences; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences; and travel reimbursement from Gilead, Bristol-Myers Squibb, and Janssen. Mayer reports unrestricted research grants from Gilead Sciences and ViiV Healthcare. Krawkower reports unrestricted research grants from Gilead Sciences. Please see the full studies for a complete list of all other authors’ relevant financial disclosures.