Revisions to the April 8, 2015, version of the guidelines are largely based on findings from two large, randomized controlled trials that addressed the optimal time to initiate antiretroviral therapy (ART) -- START (Strategic Timing of Antiretroviral Therapy) and TEMPRANO. Both studies demonstrated approximately a 50% reduction in morbidity and mortality among HIV-infected individuals with CD4 T lymphocyte cell (CD4) counts >500 cells/mm3 randomized to receive antiretroviral therapy (ART) immediately versus delaying initiation of ART. Key updates related to these studies and other significant changes are highlighted throughout the guidelines.
The following guideline sections include key updates:
Based on the START and TEMPRANO findings, the Panel on Antiretroviral Guidelines for Adults and Adolescents (the Panel) has increased the strength and evidence rating for the recommendation on initiating ART to AI for all HIV-infected patients, regardless of CD4 count. Revisions to this section focus on the data supporting ART for all patients.
Following are the updated recommendations in this section:
- ART is recommended for all HIV-infected individuals, regardless of CD4 cell count, to reduce the morbidity and mortality associated with HIV infection (AI).
- ART is also recommended for HIV-infected individuals to prevent HIV transmission (AI).
- When initiating ART, it is important to educate patients on the benefits and considerations regarding ART, and to address strategies to optimize adherence. On a case-by-case basis, ART may be deferred because of clinical and/or psychosocial factors, but therapy should be initiated as soon as possible.
The recommendation for initiation of ART in patients diagnosed with acute and recent infection has been strengthened. The changes are highlighted below:
- "Antiretroviral therapy (ART) is recommended for all individuals with HIV-1 infection and should be offered to those with early HIV-1 infection (BII)."
- "Antiretroviral therapy (ART) is recommended for all individuals with HIV-1 infection (AI) including those with early HIV-1 infection."
Following are two key updates to this section:
- The Panel noted that although the START and TEMPRANO study populations did not include adolescents, the recommendation to treat all HIV patients has been extrapolated to adolescents based on the expectation that they will derive benefits from early ART similar to those observed in adults.
- Recommendation that ART initiation in post-pubertal adolescents (sexual maturity rating [SMR] IV and V) be guided by the Adult and Adolescents Guidelines and therapy initiation in pre-pubertal adolescents (SMR I-III) by the Pediatric Guidelines.
The updated section is focused on the current recommendation to treat all patients regardless of CD4 count. The section emphasizes that ART is especially important for older patients because they have a greater risk of serious non-AIDS complications and potentially a blunted immunologic response to ART.
The list of Recommended regimens for initial ART has been expanded to include elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine for patients with estimated creatinine clearance ≥30 mL/min (AI).
More updates to the What to Start section will be forthcoming in the next revision of these Guidelines (anticipated in May or June 2016), including additional discussion of the newest recommended regimen.