HIV-positive individuals with a detectable viral load who achieve high levels of adherence to their HAART regimen are more likely to develop new drug resistance mutations than patients with a detectable viral load and poor adherence, according to a study conducted by the University of San Francisco and published in the September 5th edition of AIDS.
It should be emphasised that the findings of the study relate only to patients with incomplete viral suppression, and do not have implications for individuals who have achieved a viral load below 50 copies/mL and are highly adherent to their anti-HIV treatment regimens.
The investigators also point out that they are not advocating that patients with detectable viral loads become less adherent to their medication to avoid developing new resistance mutations, as even in the presence of resistance and a detectable viral load, high levels of adherence are still associated with a clinical benefit and delayed progression to AIDS and death.
A total of 148 HIV-positive individuals who were homeless or had unstable housing tenure were recruited to the Research on Access to Care in the Homeless (REACH) cohort at the University of San Francisco. The study participants were taking a three drug anti-HIV regimen. Every three to six weeks individuals had their adherence assessed using an unannounced pill count. Viral load was monitored every month. In the sub-set of patients with a detectable HIV viral load, blood samples obtained for genotyping six months apart.
A majority of the study participants (58%) were taking a protease inhibitor- based HAART regimen, and 48% had been previously treated with either NRTI mono or dual therapy. A history of injecting drug use was reported by over 37% of individuals.
Median adherence over the twelve months of the study was 64.7%, and the level of adherence was closely related to viral load. A viral load below 50 copies/mL was present in 25% of patients, who had mean adherence of 82% compared to 58% adherence in the patients with detectable HIV viral load.
Adherence was also closely associated with the amount of anti-HIV therapy which patients received. Individuals who took 92% - 100% of their anti-HIV drugs received a mean of 11.1 months of HAART, whilst patients who took 0 – 41% of their medication received only 6.4 months of anti-HIV therapy (p
Participants with a detectable viral load had an average of 3.2 drug resistant mutations when the first sample was obtained for genotype resistance testing. The number of mutations was associated with the length of antiretroviral therapy (p=0.02) and prior mono or dual NRTI therapy (p=0.006).
By the time the second sample was obtained for genotyping six months later, those patients whose HIV viral load remained detectable had developed a mean of 0.93 new resistance mutations. The number of new resistance mutations developed was positively associated with the level of adherence between the first and second sample obtained for genotyping (p=0.004), and the number of months of antiretroviral therapy received (p=0.005).
The investigators estimated that 23% of patients with a detectable viral load who have a level of adherence of between 82% - 100% would develop new drug resistance mutations, compared to 12% of patients who took a maximum of 41% of their doses.
”Our observations suggest that 23% of drug resistance mutations occur in individuals in the top quintile of adherence (92 – 100%), and over 50% of all drug resistance occurs in the 40% most adherent patients (79 – 100%)” conclude the investigators.
The investigators highlight several components to this conclusion. “First, the rate of accumulating drug resistance mutations increased with increasing adherence amongst patients with incomplete viral suppression. Second, individuals with high levels of adherence sustained therapy over a longer period of time than people with low levels of adherence. Prolonged therapy in the absence of complete viral suppression is more likely to create high level drug resistance to multiple classes than brief periods of therapy. Third, the proportion of people with sustained viral loads below 50 copies/mL increased with improving adherence.”
In addition, the investigators stress that their findings do not suggest that low levels of adherence should be advocated as a way of avoiding drug resistance in patients with detectable viral loads.
“High levels of adherence, even with drug-resistant virus, will likely provide more clinical benefit than either low levels of adherence or no treatment” stress the investigators, adding, “the goal remains for patients and providers to strive for exceptional levels of adherence both to delay disease progression…and to achieve reliable and durable viral suppression in order to limit the development of drug resistance as much as possible.”
Further information on this website
Adherence - factsheet
Adherence tips - factsheet
Late/missed doses - factsheet
Adherence - booklet in the information for HIV-positive people series (pdf)
Bangsberg DR et al. High levels of adherence do not prevent accumulation of HIV drug resistance mutations. AIDS 17: 1925 – 1932, 2003.