Modern HIV treatment can work well with adherence below 95%

Michael Carter
Published: 07 November 2008

Patients taking modern antiretroviral regimens still have a good chance of maintaining an undetectable viral load if their adherence is below 95%, Spanish researchers report in the October edition of AIDS Research and Human Retroviruses. They found that patients taking HIV treatment based on either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor at an adherence rate of only 80% was associated with a risk of virological failure below 10%.

This is the equivalent of missing no more than one dose in five of a once-daily combination. Ninety per cent adherence is the equivalent of missing one dose in ten - a substantial difference in the frequency of missed doses.

But the study’s authors emphasise that the goal should still be to achieve the highest possible rate of treatment adherence as there were very low rates of treatment failure even amongst patients whose level of adherence was at least 90%.

Antiretroviral therapy provides HIV-positive individuals with the chance of living a long and healthy life. However, HIV treatment is a life-long commitment and can involve side-effects. Furthermore, many patients find it difficult to sustain high levels of adherence to their antiretroviral therapy, and poor treatment adherence is associated with the emergence of drug-resistant HIV as well as an increased risk of HIV-related illness and death.

It is generally said that it is necessary to take at least 95% of HIV treatment doses at the right time and in the right way for antiretroviral therapy to have the best chance of achieving and maintaining suppression of HIV.

However, this estimate was based upon outcomes seen in patients taking older unboosted protease inhibitors, a class of drugs that is no longer recommended. Therefore researchers in Barcelona studied the level of adherence needed to maintain an undetectable viral load in patients taking antiretroviral therapy based upon NNRTIs or boosted protease inhibitors.

Their research involved 1142 treatment-naïve and treatment-experienced patients who were prescribed antiretroviral therapy between 2004 and 2005. All the patients had achieved an undetectable viral load. The study lasted one year.

These patients were divided according to the type of antiretroviral regimen they were taking: unboosted protease inhibitor (11%); boosted protease inhibitor (31%); and NNRTI (58%). Adherence was assessed by pill count during routine clinic appointments. The researchers compared the risk of viral load increasing to detectable for each of the drug classes at various levels of adherence: below 70%; 70-80%; 80-90% and above 90%. They also examined whether any treatment or patient characteristics were associated with adherence and outcome.

Most of the patients (1059) maintained an undetectable viral load for the duration of the study, and their mean level of adherence was 96%. Mean adherence for the 83 individuals who experienced a breakthrough in their viral load was 76%.

Compared to patients with 90% adherence or better, the risk of virologic failure was 9% for those with adherence between 80-90%, increasing to 46% of those with adherence between 70-80% and 77% for those who took below 70% of their doses.

At all levels of adherence below 90%, those taking an unboosted protease inhibitor were the group most likely to develop resistance (100% failure rate for adherence below 70%, 71%failure rate for adherence between 70-79%, 24% failure rate for adherence between 80-89%).

Although the failure rate for patients taking a boosted protease inhibitor and adherence below 90% was higher for patients taking a boosted protease inhibitor than those taking an NNRTI, it was not significantly so (below 70%, 50% vs. 35%; between 70-79%, 37% vs. 24%, between 80-89%, 9% vs. 6%).

The only factors associated with adherence were the number of pills (with the chances of adherence decreasing significantly as the number of pills increased, p < 0.001), and number of daily doses. However, although adherence was poorer amongst patients taking their treatment three times a day, there were no significant differences between patients taking their treatment once-daily and twice-daily.

“Our data show that virologic success is possible with less than 95% adherence”, conclude the investigators, adding, “for patients taking NNRTI- or boosted protease inhibitor-based regimens with adherence rates of 80%, the failure rate is less than 10%.”

However, the investigators found extremely low rates of treatment failure for patients with adherence above 90% (1% for those taking an unboosted protease inhibitor, 0.5% for those taking a boosted protease inhibitor and 1.4% for those taking an NNRTI) and therefore conclude, that the goal should still be to achieve “the highest rate of adherence possible.”

Reference

Marin M. Relationship between adherence level, type of antiretroviral regimen, and plasma HIV type 1 RNA viral load: a prospective cohort study. AIDS Research and Human Retroviruses 24: 1263-68, 2008.