Swiss research identifies factors associated with use of non-recommended HIV therapy

New Swiss research shows the importance of observing antiretroviral treatment guidelines, even in people who have well-controlled HIV infection. Published in the online edition of the Journal of Acquired Immune Deficiency Syndromes, the study demonstrated that toxicities and concerns about long-term side-effects were common reasons for switching to recommended treatment. CD4 cell count, viral load and adherence either remained stable or improved after the treatment change.

“Our results demonstrate the benefit of observing available cART [combination antiretroviral therapy] recommendations and suggest that recommendations should be observed even in well-controlled patients,” comment the authors.

HIV is a particularly complex area of medicine. There are expert consensus guidelines to enable physicians to prescribe the safest, most appropriate combination of anti-HIV drugs. These are updated regularly to reflect advances in HIV medicine.

Certain combinations of antiretroviral drugs are not recommended because of concerns about their safety and efficacy.

This includes the use of therapy based on double boosted protease inhibitors; treatment consisting of three nucleoside reverse transcriptase inhibitors (triple NRTI); and the combination of d4T (stavudine, Zerit) with ddI (Videx).

A team of investigators looked at the prescribing practices of HIV physicians in Switzerland between 2006 and 2010.

The retrospective study involved participants enrolled in the Swiss HIV Cohort Study who were taking antiretroviral therapy and who had an undetectable viral load.

Three non-recommended regimens in 2006 US guidelines were included in the authors’ analysis: double boosted protease inhibitors (104 participants); triple-NRTI therapy (436 participants); and a combination including d4T/ddI (21 participants). They compared the characteristics of these participants with those of 3171 individuals taking recommended regimens and looked at the factors associated with switching to recommended combinations of drugs and outcomes after changing treatment.

There were a number of significant baseline differences between participants taking non-recommended combinations and individuals prescribed standard HIV therapy.

Individuals prescribed double boosted protease inhibitors had more advanced HIV disease and were highly treatment-experienced. Their adherence was poorer and their cholesterol and triglycerides were higher, even though they were more likely to be prescribed lipid-lowering medication.

Participants in the triple-NRTI group were less likely to have advanced HIV disease and had less experience of antiretroviral treatment.

“The association between recommendation non-adherence and high CD4 count may be due to perceived level of security on the part of the prescribing physician,” suggest the investigators.  

However, participants taking triple-NRTI therapy had a higher Framingham risk score (ten-year risk of cardiovascular disease) than the control patients and most were under the care of private practitioners. The authors explain: “Private practitioners are HIV community physicians who care for less ill patients such as those on triple-NRTIs.”

Individuals prescribed d4T/ddI were more likely to be receiving care at a peripheral hospital and more than half frequently missed doses of their medication.

In September 2007, 73% of participants prescribed a double boosted protease inhibitor at baseline were still taking this regimen. The proportion had fallen to 23% in September 2010. Women and individuals with a higher CD4 cell count were more likely to continue to take this combination. All participants with diabetes or a history of cardiovascular disease switched to an alternative regimen.

Most participants taking a triple-NRTI combination remained on this regimen throughout follow-up (2007 = 86%; 2010 = 53%). Participants with a history of cardiovascular disease were more likely to switch. Those who maintained an undetectable viral load were more likely to remain on the treatment until 2010.

The proportion of participants remaining on the d4T/ddI combination fell to 47% in 2007. By 2010, just one individual was still taking these two drugs.

The most common reason for switching from a double boosted protease inhibitor was the choice of the physician (39%), followed by decision of the participant (17%), concerns about cardiovascular disease (14%) and other toxicities (10%).

Lipodystrophy (29%) was the main reason why participants stopped triple-NRTI treatment. Other common reasons included decision of the doctor (19%) and decision of the patient (11%).

Switching from d4T/ddI was most often due to a decision by the doctor (33%), followed by lipodystrophy (22%), other toxicities (11%) and concerns about cardiovascular disease (11%).

Changing to recommended therapy had benefits for participants. These included a better chance of sustaining an undetectable viral load for individuals who had been prescribed triple-NRTI treatment (p = 0.02) and a trend towards improved adherence for participants switched from d4T/ddI.

The authors suggest that these reasons show that “clinicians observe recommendations when they become ‘relevant’ to patients…clinicians seem to react to an event once it has happened, rather than switch cART as primary prevention, if patients exhibit good virological and immunological control.”

Despite this, they conclude that switching to recommended treatment has benefits for patients.

Boillat-Blanco N et al. Impact of recommendation updates in well-controlled patients on non-recommended antiretroviral therapies: the Swiss Cohort Study. J Acquir Immune Defic Syndr, online edition. DOI: 10.1097/QAI.0b013e31827b26a, 2012.