Do Once-Daily Regimens Improve Adherence to Antiretroviral Therapy?

On July 12, the Food and Drug Administration approved the Atripla (tenofovir/ emtricitabine/ efavirenz) combination pill, the first-ever one-pill, once-daily antiretroviral regimen. Enthusiasm for once-daily therapy stems from the hope that more convenient regimens will improve adherence, and thereby reduce the development of drug-resistant HIV.

A study reported in the June 2006 Journal of Acquired Immune Deficiency Syndromes lends support to the idea that simplified therapy is associated with better adherence.

From July through September 2005, the researchers conducted a survey of HIV positive people to investigate their preferences regarding antiretroviral therapy. A questionnaire was posted on the web site of a large Italian non-profit HIV/AIDS organization (www.nadironlus.org), which receives more than 40,000 hits per month. The same questionnaire was also administered during in-person interviews at six Italian clinical centers.

The respondents were asked:

The type of antiretroviral therapy they were taking;

The number of previous regimens used;

The number of daily doses;

Their preferred type of antiretroviral formulation;

Self-reported missed doses;

Problems related to therapy;

Where they seek information about antiretroviral drugs;

How they collaborate with their physician to choose a regimen.

Participants were asked whether they would like simpler therapy. If they answered yes, they were asked whether they would prefer fewer pills or fewer daily doses.

Results

416 individuals completed the questionnaire (229 via the web and 187 during face-to-face interviews); of these, 82% were taking HAART. The mean age was 32 years, 28% were women, and 32% were HCV/HIV coinfected.

Among participants taking HAART, the most commonly used medications were:

- AZT (Retrovir) plus 3TC (Epivir), 35%;
- tenofovir (Viread), 30%;
- efavirenz (Sustiva), 22%;
- nevirapine (Viramune), 18%;
- lopinavir/ritonavir (Kaletra), 19%;
- atazanavir (Reyataz), 10%.

30% were taking their first HAART regimen, 23% were on their second regimen, 17% were on a third regimen, and 30% had tried four or more regimens.

18% were taking once-daily regimens, 70% were on twice-daily regimens, 11% were on a thrice-daily regimen, and 1% took antiretrovirals more than three times daily.

More than 90% said they would like to simplify their therapy.

52% said they would like to reduce the number of pills they took each day, while 39% said they would like a reduced number of daily doses.

Just over 7% reported they were non-adherent, defined as missing at least one dose in the previous week.

No difference in the rate of non-adherence was noted between respondents taking once-daily and twice-daily regimens.

Among respondents taking twice-daily regimens, 13 out of 18 non-adherent respondents (72%) said they would prefer a reduced number of doses, compared with 87 out of 198 adherent respondents (44%) (P = 0.02).

Non-adherence was more common among patients taking their third or a subsequent regimen, compared with people on their first or second regimen (P = 0.001).

Non-adherence was also more common among participants who reported body shape changes (P = 0.055), and among those who preferred a reduced number of doses rather than fewer pills daily (P = 0.045).

154 respondents (37%) reported some problem with therapy:

- adverse events, 42%;
- body shape changes, 32%;
- too many pills, 24%;
- too many doses, 2%.

Participants reported seeking information on antiretroviral drugs from:

- a physician, 73%;
- the web, 65%;
- HIV/AIDS organizations, 36%;
- the media, 30%.

Conclusion

Based on the survey results, the researchers concluded that the main concerns of HIV positive people taking HAART are related to tolerability of drugs and body shape changes. Desire for a reduced number of doses seemed to be a major issue only for a small proportion of respondents. However, a significant proportion of individuals taking twice-daily regimens who preferred a reduced number of daily doses reported less-than-optimal adherence. For these patients, the authors wrote, "the simplification of therapy may represent a crucial strategy to achieve the best results in terms of adherence improvement."

However, they suggested that overall satisfaction with therapy was influenced by a combination of factors, including tolerability, visible side effects, and number of pills. They added that patients who actively seek information on antiretroviral therapy and those who play a more active role in the patient-physician relationship had the best chances of receiving more convenient regimens.

7/18/06

Reference
R Murri, S Marcotullio, P Lupoli, and F von Schloesser. Is "Once-Daily" Regimen a Key Strategy for Improving Adherence to Antiretroviral Regimens? [Letter to the Editor]. Journal of Acquired Immune Deficiency Syndromes 42(2): 259-260. June 2006.