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IAS 2013: Single Tablet Regimens Do Not Always Produce Better HIV Treatment Outcomes

One pill per day does not necessarily lead to more durable HIV suppression than regimens containing more pills taken twice-daily, according to a study presented at the recent 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur.

Single-tablet regimens (STRs) containing a complete combination antiretroviral regimen in a once-daily coformulated pill are considered a breakthrough in treatment simplicity and convenience. Some studies have found that they promote better adherence, which is associated with reduced risk of virological failure and disease progression.

The currently approved STRs -- Atripla (efavirenz/tenofovir/emtricitabine), Complera (rilpivirine/tenofovir/emtricitabine), and Stribild (elvitegravir/cobicistat/tenofovir/emtricitabine) -- are highly effective and generally well-tolerated, though many people experience central nervous side effects caused by efavirenz.

Benoit Trottier from Clinique Medicale L'Actuel in Montréal and colleagues conducted a retrospective analysis of patients who started ART since 2007. Their aim was to compare regimens that maximize convenience versus those with minimal side effects. Some prior studies have found that absence of toxicities is a more important factor for regimen durability than simplicity, they noted as background.

The study included 575 patients at their clinic who started one of 4 recommended first-line ART regimens:

• Atripla STR (efavirenz/tenofovir/emtricitabine);
• Boosted atazanavir (Reyataz) plus 2 NRTIs;
• Boosted darunavir (Prezista) plus 2 NRTIs;
• Raltegravir (Isentress) plus 2 NRTIs.

More than 90% of participants were men and the median age was about 40 years. The median baseline CD4 T-cell count was approximately 300 cells/mm³, with 16% having <200 cells/mm³.

The primary endpoint was time until discontinuation of the first-line regimen, though NRTI backbone changes were allowed for those using non-STR combinations. The secondary endpoint was time to loss of virological response. The median duration of follow-up was just under 3 years.

Results

• Overall, approximately one-third of participants discontinued their regimen during follow-up.
• The most common reason for discontinuation was drug side effects or toxicities.
• Rates of discontinuation were statistically similar for people using Atripla (35%) and those using non-STR regimens (31%).
• Treatment duration was statistically equivalent between Atripla and non-STR regimens.
• After adjusting for other factors, people who started on raltegravir were less likely to change their regimen than those who started on either Atripla or one of the protease inhibitors.
• Injection drug use history and high baseline viral load were also associated with greater likelihood of switching regimens.
• People who started Atripla were significantly more likely to maintain virological suppression than those taking any non-STR regimen.
• Atripla and raltegravir, however, were associated with similar response rates.
• Use of atazanavir or darunavir, as well as injection drug use, predicted loss of virological response.

"Our findings suggest that [single-tablet regimens] do not necessarily result in a more durable treatment," the researchers concluded. "Even with a higher pill burden and multiple doses, a 2 NRTI + raltegravir regimen is more durable" than Atripla or the other combinations.

"The main reason for first line discontinuation/switch remain the adverse drug effects, very few virological failure[s] were observed," they continued. However, Initiating antiretroviral treatment with a STR or raltegravir-based treatment "seems to provide a longer virological control compared to other non-STR regimens studied."

These findings are limited to the specific drugs in Atripla and may not apply to other available STRs, which do not contain efavirenz. However, those coformulations are still too new to allow for such a large retrospective comparison.

8/7/13

Reference

B Trottier, N Machouf, R Thomas, et al. Single tablet regimens do not necessarily translate into more durable HIV treatments. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract TUPDB0106.