For HIV care providers, one of the most debated questions has been when to start antiretroviral therapy for patients living with HIV. In particular, when to start treatment depended on a number of factors when caring for newly diagnosed patients, especially those with higher CD4+ cell counts. However, now the answer to when to start is the same for all patients, including those newly diagnosed.
When to Start
In May 2015, the landmark Strategic Timing of AntiRetroviral Treatment (START) study definitively answered the "when to start" question when researchers stopped it 18 months early because of overwhelming results: Starting treatment immediately regardless of CD4+ cell count was more beneficial than waiting until the CD4+ cell count dropped.
START was a global study with 215 sites in 35 countries and a diverse study population of 4,685 treatment-naive patients living with HIV. At IAS 2015, the final results were presented, which showed that there was a significant reduction in AIDS and non-AIDS events for those who started treatment immediately compared with those who waited until their CD4+ cell counts dropped below 350.
At the same time, the TEMPRANO study, which followed over 2,000 HIV-positive patients in Cote d'Ivoire, also found that starting treatment immediately lowered the risk of death, AIDS and non-AIDS events.
Treatment Guideline Recommendations
In light of these two randomized controlled trials, the U.S. Department of Health & Human Services (HHS), which since 2012 has recommended starting treatment for everybody regardless of CD4+ cell count, upgraded this recommendation from A2 to A1 -- the strongest rating -- in its HIV treatment guidelines.
In Sept. 2015, the World Health Organization (WHO) followed suit and released an early update to its guidelines, which now also recommend starting antiretroviral therapy for all individuals living with HIV regardless of CD4+ cell count. Previously, the WHO had recommended treatment only for those whose CD4+ cell counts dropped below 350, and for certain patients with CD4+ cell counts between 350 and 500.
What to Start
With a treat-all approach in place, the next question is what to start. According to the latest HHS HIV treatment guidelines, updated in April 2015, there are five recommended regimens for treatment-naive patients: four integrase inhibitor-based regimens and one boosted protease inhibitor regimen.
The five recommended regimens are:
- Abacavir/dolutegravir/lamivudine (Triumeq) -- only for patients who are HLA-B*5701 negative;
- Dolutegravir (Tivicay, DTG) plus tenofovir/emtricitabine (Truvada);
- Elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild) -- only for patients with pre-treatment creatinine clearance > 70 mL/min;
- Raltegravir (Isentress) plus tenofovir/emtricitabine;
- Darunavir (Prezista) boosted with ritonavir (Norvir) plus tenofovir/emtricitabine.
Two popular regimens that were previously classified as recommended were moved to the alternative regimens category, with the following rationale as described in the guidelines:
- Ritonavir-boosted atazanavir (Reyataz) plus tenofovir/emtricitabine -- based on the results of a large comparative clinical trial showing a greater rate of discontinuation with ritonavir-boosted atazanavir plus tenofovir/emtricitabine because of toxicities when compared to ritonavir-boosted darunavir or raltegravir, plus tenofovir/emtricitabine;
- Efavirenz/tenofovir/emtricitabine (Atripla) -- Based on concerns about the tolerability of efavirenz in clinical trials and practice, "especially the high rate of central nervous system (CNS)-related toxicities and a possible association with suicidality."
"[I]t comes down to progress we've made in improving side effects. Many choices are available now that are simply easier for patients -- and clinicians, who can skip the time on pre-treatment education and management of tricky side effects," wrote Paul Sax, M.D., a member of the HHS treatment guidelines panel, in a blog entry about the changes.
As with any treatment, the choice depends on the desired coformulation and dosing schedule, as well as potential drug-drug interactions and drug resistance.
Although it seems straightforward to simply start treatment for all newly diagnosed patients using one of the five recommended regimens, providers should keep in mind that an HIV diagnosis is a stressful, life-changing event for any patient.
In addition to the mental and emotional trauma of a diagnosis, starting treatment is a lifelong commitment that can be a physical and financial burden. Providers should carefully work with patients to help keep adherence high. Be sure to discuss with patients what works best for them and to direct them to the best available resources when needed.