Adherence levels are high and even seem to improve in patients taking long-term antiretroviral therapy, UK investigators report in the online edition of AIDS.
An analysis of over 2000 patients with up to nine years of follow-up showed that, not only did the majority of patients remain adherent to their antiretroviral therapy, but that the chances of a patient remaining adherent increased by about 2% a year.
“These encouraging observations have implications for our understanding of the likelihood that patients will be able to maintain sufficient levels of adherence for a lifetime,” comment the investigators from London’s Royal Free Hospital.
Treatment with combination antiretroviral therapy can significantly extend the prognosis of HIV-positive individuals. HIV treatment works by inhibiting HIV replication, and the target of therapy is an undetectable viral load (below 50 copies/ml).
Very high levels of adherence (at least 95%) are needed to achieve and maintain an undetectable viral load. Lower levels of adherence have been associated with an increase in viral load, the emergence of resistant strains of HIV, a fall in CD4 cell count and an increased risk of illness and even death.
Some research has suggested that levels of adherence to HIV treatment diminish the longer a patient receives it. But these studies have been small and have generally had a follow-up period of less than three years.
Therefore investigators at the Royal Free Hospital in London monitored adherence levels in their cohort of 2060 patients who have received therapy with anti-HIV drugs.
Adherence was monitored in six-monthly periods, and adherence was defined as the proportion of days in that period covered by antiretroviral drugs.
Patients were assessed for a median of 4.5 years, the longest duration of follow-up being nine years. A total of 16,545 six-month adherence periods were available for analysis.
Most of the patients were male (78%), white (66%), and maintained an undetectable viral load for the duration of follow-up (79%).
Median coverage of HIV treatment during the study was 92%. This remained stable throughout the study.
Far from declining, there was a trend suggesting that adherence increased the longer a patient received treatment (OR = 1.02; 95% CI, 1.01 to 1.04; p = 0.0533).
Factors associated with poorer adherence included being a black heterosexual man (p = 0.0153). The investigators suggest, “this is likely to relate to socioeconomic and migration status, characterised by more difficult access to care, and perhaps less access to information.”
Individuals who had experienced three or more virologic treatment failures were significantly less likely to be adherent than individuals who had always maintained an undetectable viral load (p < 0.0001).
Increasing age was significantly associated with better levels of adherence (p < 0.0001). The investigators suggest that older patients are more likely to attend their clinic appointments and “are more aware of the negative clinical effects of low adherence”.
Combinations including boosted atazanavir (Reyataz) or boosted saquinavir (Invirase) were associated with good adherence levels. This could be an indication of the better tolerability of more modern antiretroviral drugs, a theory supported by the finding that adherence levels were poorer in the early periods of the study (p = 0.0003).
There was also evidence that adherence levels predicted engagement with HIV care. Patients with poor levels of adherence (below 60% drug coverage) were significantly more likely to be lost to follow-up than those with the best levels of adherence.
However, the researchers found that 48% of patients experienced one period of poor adherence, although this was often a one-off event.
“We found no evidence of a decrease in average levels of adherence to HAART [highly active antiretroviral therapy] over time, and even some evidence of a small increase,”, comment the investigators.
The levels of adherence observed in the study are, the investigators note, consistent with the high proportion of patients with an undetectable viral load in the cohort.
Some research suggests that an undetectable viral load can be achieved and maintained with adherence levels below 95% with some newer antiretroviral drugs.
However, the investigators suggest that the highest possible level of adherence should always be the target. This not only means that there is a very low risk of treatment failure and resistance, but also that HIV levels in genital secretions are suppressed, thereby reducing the risk of sexual HIV transmission.
“Adherence to antiretroviral therapy is generally high in routine practice and does not have a tendency to decline over … long periods, providing encouragement that maintenance of adherence for a lifetime may well be possible," conclude the investigators.