Early antiretroviral therapy for HIV advised in new guidelines

Antiretroviral therapy (ART) should be offered to all patients as soon as possible, regardless of CD4 cell count, because earlier ART may lead to improved outcomes, according to new recommendations presented during AIDS 2012, the 19th International AIDS Conference, held in Washington, D.C. The new guidelines, published online July 25 in JAMA: The Journal of the American Medical Association, include recommendations on changes in therapeutic options and modifications in the timing and choice of ART in the setting of opportunistic illnesses.

Improvements and updates

According to the panel, evidence indicates that ART reduces the likelihood of HIV transmission while providing clinical benefit to treated individuals.

"The concentration of HIV in both blood and seminal plasma correlates with the probability of transmission of HIV to a sexual partner. Reducing levels of HIV with ART decreases the probability of transmission, as confirmed in the HPTN 052 study, in which ART was 96% effective in reducing HIV transmission," the authors stated.

Therapy can be offered, regardless of CD4 cell count, as long as a patient is ready and willing to adhere to the regimen. "Clinicians should engage supportive services as needed to assist with ART education and to address barriers to adherence," the authors wrote.

Initial recommendations

The initial recommended regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir).

Both tenofovir and emtricitabine are available as a once-daily fixed-drug combination and have no food restrictions. Tenofovir has been well tolerated but has been associated with kidney injury. Before using tenofovir, renal function needs to be assessed and then monitored over time. Tenofovir should be discontinued when the eGFR is less than 30 mL/min.

Prescribers should consider convenience for the patient, potential toxicities, and the ability to continuously suppress HIV. Interactions among drugs also are a growing challenge, the authors noted.

The strength of the recommendation increases as CD4 cell count decreases and in the presence of certain conditions, such as pregnancy, chronic hepatitis B virus (HBV) coinfection, hepatitis C virus (HCV) coinfection, age older than 60 years, and HIV-associated nephropathy. The guidelines offer alternatives for patients with or at risk of these concurrent conditions and add that patients should be monitored for their CD4 cell count, as well as for HIV-1 RNA levels, ART adherence, HIV drug resistance, and quality-of-care indicators.

A lifelong commitment

The authors warn that treatment should not be interrupted except for clinical trials, surgery, severe illness, or serious drug toxicity. Regimens may be switched for reasons that include virologic, immunologic, or clinical failure and drug toxicity or intolerance; however, treatment failure should be confirmed and addressed immediately, and all potential contributory factors should be considered to prevent further evolution of drug resistance.

"The aim of therapy continues to be maximal, lifelong, and continuous suppression of HIV replication to prevent emergence of resistance, facilitate optimal immune recovery, and improve health," the authors wrote. "Although it is crucial to intensify efforts to find a cure for persons who are already infected and an effective vaccine for those who are not, many of the tools needed to control the HIV/AIDS pandemic are already at hand. Critical components of the toolkit to eradicate AIDS include expanded HIV testing, increased focus on engagement in HIV care, early and persistent access to ART, and attention to improving ART adherence. These must occur in the context of strategies to address social determinants of health, including the elimination of stigma and discrimination."

Heather Onorati is a freelance medical writer based in Cleveland, Ohio.