Modern NNRTI regimens can be effective with 85% adherence

Some modern HIV treatment regimens can achieve viral suppression with adherence rates as low as 85%, investigators from the US Veteran Aging Cohort Study report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The authors monitored trends in adherence and viral suppression between 2001 and 2010. Both adherence and rates of viral suppression improved over the course of the study. Moreover, significant increases in rates of viral suppression were observed among people with less than perfect adherence, especially when individuals were taking therapy based on a non-nucleoside reverse transcriptase inhibitor (NNRTI).

“Our data suggest that adherence levels lower than 95% may be sufficient for viral suppression in populations using newer NNRTI formulations,” write the authors, “85-89% adherence on NNRTI-based regimens may be sufficient for viral suppression.”

The goal of HIV therapy is an undetectable viral load. The proportion of people achieving viral suppression (defined in the present study as viral load below 400 copies/ml) has increased dramatically in recent years. This is due in part to improvements in anti-HIV drugs. Modern antiretrovirals have a good safety profile with a powerful and durable anti-HIV effect. In addition, most have simple dosing schedules and a number of fixed-dose combination pills are now available that provide effective treatment in a single daily pill.

Glossary

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

retention in care

A patient’s regular and ongoing engagement with medical care at a health care facility. 

integrase inhibitors (INI, INSTI)

A class of antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs) block integrase, which is an HIV enzyme that the virus uses to insert its genetic material into a cell that it has infected. Blocking integrase prevents HIV from replicating.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

Research involving people taking older anti-HIV combinations suggested that it was necessary to take at least 95% of doses at the right time and in the right way to have the best chances of achieving an undetectable viral load. But it’s unclear if modern combinations require such a high level of adherence.

To answer this question, investigators monitored rates of adherence and viral suppression among 22,000 HIV-positive veterans over a ten-year period. The authors especially wanted to see if the level of adherence needed to achieve an undetectable viral load differed between regimens based on NNRTIs, protease inhibitors and newer agents such as integrase inhibitors. Adherence was assessed using pharmacy refill. The researchers acknowledged this is a less than perfect way of assessing pill taking, but believe it to be more reliable than patient recall.

Participants had a median baseline age of 46 years and contributed approximately 82,000 person-years of follow-up.

The proportion of people taking complicated, multi-drug protease inhibitor or NNRTI-based regimens declined during follow-up from 65% to 43%, and from 33% to 16%, respectively.

In 2006, only 1% of patients were taking single-pill NNRTI-based therapy (emtricitabine/tenofovir/efavirenz), but this had increased to 29% by 2010. Therapy containing an integrase inhibitor was used by 11% of patients in 2010.

The proportion of people with 95% or better adherence increased from 37% in 2001 to 42% in 2010. The authors described this increase as “marginal.”

People taking NNRTI-based regimens were more likely to have near-perfect adherence than individuals taking combinations containing a protease inhibitor. Users of single-pill therapy had better adherence than people taking multi-pill regimens.

Analysis of people with adherence below 95% showed the proportion with viral suppression increased from 38% in 2001 to 94% in 2010. An increase in rates of viral suppression was observed even among people with adherence as low as 70-75%.

The proportion of people with sustained viral suppression increased from 78% in 2001 to 92% in 2010.

Overall, the chances of achieving viral suppression were the same for people with adherence of 90-94% and people with adherence above 95%.

Comparison of patients according to regimen type showed that, at all adherence levels, rates of viral suppression were higher among individuals on NNRTI therapy.

For people taking a protease inhibitor, adherence above 95% was associated with the highest rates of viral suppression, and poorer outcomes were observed even when patients were taking between 90-94% of their doses.

However, for people taking NNRTI-based therapy, an adherence level of 85% was associated with just as high a chance of achieving an undetectable viral load as an adherence rate of 95% or above.

“Providers should not let concerns regarding barriers to adherence hinder the prescription of newer HAART regimens at early stages of disease,” suggest the authors. “Efforts must be made to maximize the prescription and use of single pill regimens. Future work should focus on the use of other approved single pill regimens and newer drugs now included as recommended regimens in more recent guidelines, and their use in populations with poor access to and retention in care.”

References

Viswanathan S et al. Adherence and HIV RNA suppression in current era of highly active antiretroviral therapy (HAART). J Acquired Immune Defic Syndr, online edition. DOI: 10/1097/QAI.0000000000000643, 2015.