Antiretroviral Agents for HIV: Guidelines Updated

March 27, 2013

The Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents has issued updates of its recommendations.

Antiretroviral therapy (ART) for the treatment of patients with HIV infection has dramatically reduced HIV-associated morbidity and mortality and transformed HIV disease into a chronic, manageable condition, according to the Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. In addition, effective treatment of HIV-infected patients with ART is highly effective at preventing transmission to sexual partners.

However, fewer than one-third of HIV-infected persons in the United States have suppressed viral loads, mostly because of undiagnosed HIV infection and failure to link or retain diagnosed patients in care, the panel noted. Also, despite improvements in HIV treatment and prevention, economic and social barriers persist that result in continued morbidity, mortality, and new HIV infections.

Therefore, the panel-a working group of the Office of AIDS Research Advisory Council-has issued updates of its recommendations in the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. The following key changes were made:

Drug-resistance testing. In persons for whom integrase strand transfer inhibitor (INSTI)-based regimens are not successful, the panel recommends that a genotypic assay for INSTI resistance be performed to determine whether to include a drug from this class in subsequent regimens. Previously, the panel recommended that INSTI resistance testing be considered in this setting.

Co-receptor tropism assay. A genotypic tropism assay is now commercially available that predicts HIV-1 co-receptor usage based on sequencing of the V3-coding region of HIV-1 env, the principal determinant of co-receptor usage. The panel recommends that a genotypic tropism assay be used as an alternative to a phenotypic tropism assay before initiation of a CCR5 antagonist–containing regimen.

Initiating ART in treatment-naive patients. Updated recommendations include the following:

• ART is recommended for all HIV-infected persons to reduce the risk of disease progression. The strength and evidence for this recommendation vary by pretreatment CD4 cell count.

• ART also is recommended for HIV-infected persons for preventing the transmission of HIV. The strength and evidence for this recommendation vary by transmission risks (perinatal transmission, heterosexual transmission, or other transmission risk groups).

• Patients starting ART should be willing and able to commit to treatment and understand the benefits and risks of therapy and the importance of adherence. They may choose to postpone therapy, and providers may elect to defer therapy on the basis of clinical or psychosocial factors or both.

What to start: Initial combination regimen for antiretroviral-naive patients. The following changes and updates were made:

• A rilpivirine-based regimen is recommended as an alternative NNRTI-based regimen only in patients with pretreatment HIV RNA at 100,000 copies/mL or less. This is based on results from clinical trials that show that that the proportion of patients who experienced virologic failure at 96 weeks was greater in patients with pretreatment HIV RNA at more than 100,000 copies/mL than in patients with pretherapy HIV RNA at 100,000 copies/mL or less.

• Elvitegravir/cobicistat/tenofovir/emtricitabine as a fixed-dose combination product is recommended as an alternative regimen for ART-naive patients with pretreatment creatinine clearance greater than 70 mL/min.

• The discussion on 3-NRTI regimens was removed from this section because 3-NRTI regimens are no longer recommended for ART-naive patients.

Acute and recent (early) HIV infection. The following changes were made:

• The term "early” HIV infection is now used when describing both the acute phase of HIV infection (immediately after HIV infection and before seroconversion) and recent HIV infection (within first 6 months).

• The recommendation for initiation of ART in patients with early infection was changed from “should be considered optional” to “should be offered.”

• The section was updated to include a summary of recent randomized controlled trials that examined the role of time-limited ART in patients with early HIV infection.

HIV-infected women. The following changes were made:

• The recommendation on the use of efavirenz during pregnancy was updated to be in accord with the recommendation in the Perinatal Antiretroviral Guidelines. The key update includes the following statement: “Because the risk of neural tube defects is restricted to the first 5 to 6 weeks of pregnancy and pregnancy is rarely recognized before 4 to 6 weeks of pregnancy, EFV can be continued in pregnant women receiving an EFV-based regimen who present for antenatal care in the first trimester, provided the regimen produces virologic suppression.”

• The panel also recommends that intravenous zidovudine use during labor may be omitted in women who have HIV RNA at less than 400 copies/mL near delivery. Oral combination ART should be continued during labor.

Drug-drug interaction. The following change was made:

• This section includes new information under the heading “Pharmacokinetic Enhancing.” The additional text describes the roles and mechanisms of ritonavir and cobicistat as pharmacokinetic enhancers to increase the exposure of antiretroviral drugs.