Early adherence to ART key to long-term virological outcomes

Adherence to antiretroviral therapy (ART) in the first few months after starting treatment is crucial to the long-term outcomes, French research published in the online edition of the Journal of Acquired Immune Deficiency Syndromes suggests. People who took all or nearly all their doses in the first four months after initiating ART were approximately four times more likely to have prolonged viral suppression in up to 12 years of follow-up, compared to people who frequently missed doses. Findings also showed the importance of maintaining high levels of adherence during long-term therapy.

“This unexpected long-term virological impact of early adherence reinforces the message that, when starting antiretrovirals, all means should be mobilized to ensure optimum early adherence to achieve prolonged antiretroviral success,” comment the authors.

Adherence is the single most important factor under the control of people living with HIV that determines the success of ART. The aim of treatment is an undetectable viral load, an outcome associated with adherence levels of at least 95% with older anti-HIV drugs (though modern therapies are more forgiving of missed doses).

Investigators from the prospective, multi-centre, French APROCO-COPILOTE cohort wanted to see if very early adherence to ART (the first four months of treatment) was associated with longer-term viral suppression (up to 12 years of follow-up).

The study population consisted of 891 people who initiated ART based on a first-generation protease inhibitor between 1997 and 1999. They were followed for a mean of nine years and a median of eleven years.

Self-reported adherence data were collected four months after the initiation of treatment. Adherence was “high” if people took 100% of their doses, medium if 99.9% to 80% of doses were taken and low if below 80% of doses were taken in the previous four days. Further data on adherence were collected at regular intervals during follow-up.

Baseline characteristics were as follows: median age was 37 years, 21% of people were female, 20% had AIDS, the median CD4 cell count was 286 cells/mm³ and median viral load was 29,000 copies/ml.

The proportion of people with prolonged virological suppression increased from 48% at the 20-month follow-up intervals to 73% after 12 years of therapy.

At month 4, 57% of people had high adherence, 33% had medium adherence and 10% had poor adherence. During follow-up, 66% of people maintained high adherence, 25% fluctuated between high and medium adherence and 9% had at least one episode of low adherence.

There was clear evidence that early adherence was associated with long-term outcomes.

High and medium adherence versus low adherence at month 4 of therapy was significantly associated with increased chances of prolonged virological suppression (adjusted OR 3.73; 95% CI 1.98-6.98).

Maintaining good adherence was also associated with better virological outcomes between months 20 and 144 after treatment initiation. Compared to people with an episode of poor adherence, individuals with high and moderate adherence were over three (adjusted OR 3.28; 95% CI 2.64-4.08) and two (adjusted OR 2.26; 95% CI 1.81-2.83) times more likely to have persistent viral suppression.

“Targeted interventions for enhancing adherence need to be implemented both at ART initiation, and over the course of treatment,” write the authors.

They call for further studies looking at the impact of early adherence on long-term outcomes with modern, more potent antiretrovirals that are more forgiving of missed doses.