1 in 5 People on Atripla Switch, Usually Due to Central Nervous System Side Effects

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One-fifth of all people who start the Atripla (efavirenz/tenofovir/emtricitabine) combination pill eventually may need to change to a different regimen, most often due to neuropsychiatric symptoms such as insomnia, abnormal dreams, dizziness, anxiety, or depression, according to a study described in the July 17, 2012, issue of AIDS.

The once-daily Atripla single-tablet regimen is highly effective at suppressing HIV and is very convenient for patients, making it one of the most popular choices for people starting HIV treatment for the first time. Though generally safe, a significant proportion of patients develop central nervous system (CNS) side effects related to efavirenz (sold separately as Sustiva). These symptoms are often worse soon after starting the drug and improve over time, but in some cases they persist.

While Atripla remains among the most widely prescribed antiretroviral regimens, the advent of the Complera single-tablet regimen (rilpivirine/tenofovir/emtricitabine) in 2011 and the recent FDA approval of the 4-in-1 Stribild "quad" pill (elvitegravir/cobicistat/tenofovir/emtricitabine) offer new options for convenient first-line therapy. (Atripla, Complera, and Stribild are all marketed by Gilead Sciences.)

Andrew Scourfield, Mark Nelson, and colleagues fromChelsea and Westminster Hospital and Imperial College in London performed a retrospective case-based analysis of all 472 participants in a London HIV cohort who had received Atripla as their first antiretroviral regimen. For individuals who discontinued Atripla, they collected data about the emergence and progression of adverse events.

Most participants (94%) were men, about 75% were white, and the median age was 37 years. The median CD4 T-cell count at treatment initiation was 285 cells/mm3.

Results

o   Nightmares or vivid dreams: 44%;

o   Insomnia 43%;

o   Depression: 35%.

o   Liver toxicity: 8%;

o   Skin rash: 7%;

o   Virological failure or resistance: 7%;

o   Pregnancy: 3% (efavirenz is considered contraindicated for pregnant women due to potential for birth defects);

o   Participation in a switch research trial: 2%;

o   "Lifestyle" issues, e.g., drug or alcohol use: 2%;

o   Gastrointestinal side effects: 1%;

o   Drug-drug interaction: 1%.

o   6 people (10%) switched within the first 4 weeks;

o   4 people (6%) did so between 4 and 12 weeks;

o   30 people (48%) did so between 12 and 52 weeks;

o   23 people (36%) did so a year or more after starting Atripla (52 to 96 weeks).

"One-fifth of all individuals commencing Atripla will need to switch therapy, often for adverse events," the study authors concluded. "The commonest reason for switch in our cohort was CNS toxicity, which although it may develop shortly after initiation may persist, ultimately leading to discontinuation of Atripla months or years later."

"Higher rates of CNS toxicity have been reported in those with African ancestry due to polymorphisms of cytochrome P450 2B6 (CYP2B6)," an enzyme that metabolizes drugs in the liver, the researchers elaborated in their discussion. "[H]owever, our data showed no increased prevalence of CNS toxicity in this ethnic group and no association with nadir [lowest-ever] CD4 cell count."

"It is noteworthy that 3 individuals discontinued antiretroviral therapy without consultation due to CNS side effects, 1 of these presented with Pneumocystis carinii pneumonia and 1 with detectable resistance mutations," they warned. "Another 3 individuals took deliberate overdoses in suicide attempts that they directly attributed to their CNS toxicity (1 of these was on treatment for hepatitis C)."

"With the advent of new combination tablets and treatment strategies, physicians should elucidate whether individuals have continuing CNS toxicity on Atripla as this group may benefit from alternative agents," they recommended.

10/16/12

Reference

A Scourfield, J Zheng, S Chinthapalli, M Nelson, et al. Discontinuation of Atripla as first-line therapy in HIV-1 infected individuals. AIDS 26(11):1399-1401. July 17, 2012.