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
Participants in the triple-NRTI group were less
likely to have advanced HIV disease and had less experience of antiretroviral
“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
Despite this, they conclude that switching
to recommended treatment has benefits for patients.