Having to take a large number of pills as part of a HAART regimen is associated with poor adherence, stopping or changing treatment, and virological and immunological responses in individuals starting HIV for the first time with a protease inhibitor based regimen, according to a large multicentre US study presented as a poster to the Second International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris. Also presented as a poster at this conference is another US study showing that transient viral load blips have no connection to lapses in adherence.
NNRTI regimens and new formulations of protease inhibitors have substantially reduced HAART pill burden in the last few years, however pill burden is recognised as a potential factor leading to suboptimal levels of adherence. Viral load blips have been the subject of some controversy, and although it is thought that most are caused by lab error, some studies have suggested that transient rises in viral load can be predictive of more sustained viral rebound.
This study pill burden was conducted by San Francisco General Hospital, University College San Francisco in association with the drug company Bristol Myers Squibb. Study objectives were to assess the proportion of patients achieving adherence of at least 90%, the proportion changing regime or changing treatment, and the number achieving viral load suppression below 50 copies/mL and a CD4 cell increase of at least 100 cells/mm3.
Adherence was assessed by looking at the number of 30 day prescription refills which a patient obtained over a twelve month period. Obtaining eleven refills was regarded as being indicative of 90% adherence.
At baseline, patients had an average age of 40 years, mean CD4 cell count was 347 cells/mm3 and viral load was a little over 100,000 copies/mL. Depression was diagnosed in 12% of patients. Patients recruited to the study from the HIV Insite database between 1995 and 2002.
Indinavir was the most commonly used protease inhibitor, forming the basis of anti-HIV therapy in 46% of patients. Saquinavir was used by 20% of individuals, nelfinavir by 18%, ritonavir by 12.5%, with less than 1% using either amprenavir, lopinavir or hard-gel saquinavir.
Only 40% of patients achieved 90% adherence, and only 36% experienced a fall in HIV viral load below 50 copies/mL. Treatment was stopped or changed by 65% of patients.
Investigators found that a decreased pill burden (p=0.1) predicted adherence of at least 90%, and that increased pill burden (p3.
The investigators conclude that increasing pill burden is an independent predictor of lower adherence, and poor immunological and virological outcomes from HAART.
Investigators at UCLA assessed the relationship between adherence and transient blips in viral load in 128 HAART-treated patients. Adherence was measured using electronic medicine bottle caps. A viral load blip was defined as an increase in viral load from a previously undetectable level to a detectable, but low level (below 1000 copies/mL), with a return to undetectable levels when viral load was next tested.
A total of 28 blips were observed in the study, which tested viral load on a monthly basis. Adherence in the month before the last undetectable viral load before the blip was 86%, 84% in the month of the blip, and 80% in the month after the blip when viral load returned to normal. Although such levels of adherence would be regarded as suboptimal, they were higher than the adherence seen in control patients who maintained an undetectable viral load for a three month period (77%, 79% and 75%, p=0.046).
When adherence was compared on a weekly basis between blippers and control patients, it was found that, once again, individuals experiencing transient increases in viral load had higher adherence.
The investigators conclude: "We found no evidence that adherence lapses or variance in dose timing are associated with blips" and called for further research into the immunological, drug-related, and other factors involved in viral load blips.
Dansburg DR et al. Pill burden predicts adherence, regimen discontinuation or switch, viral load, and CD4 cell response in a nationwide US sample of HIV+ antiretroviral naïve people on protease inhibitor (PI) therapy. Antiviral Therapy 8 (suppl.1), abstract 757, 395, 2003.
Miller LG et al. Episodes of transient HIV viremia (blips) are not associated with drops in medication adherence. Antiviral Therapy 8 (suppl.1), abstract 761, 396, 2003.