Adherence to HIV treatment significantly increases survival, researchers find

(Medical Xpress)—HIV-positive individuals who strictly adhere to highly active antiretroviral therapy (HAART) have a significantly lower probability of premature morbidity and mortality as compared to those with suboptimal compliance to HAART, according to a new study from the BC Centre for Excellence in HIV/AIDS (BC-CfE).

The study, published this week in the peer-reviewed journal PLOS ONE, investigated 3,543 HIV-infected individuals who were more than 19 years old and had never been on HAART when they started treatment between January 1, 2000 and August 31, 2009. Participants were followed until their death due to any cause, or if alive, until the last contact date or August 31, 2010, whichever came first. At the end of the follow-up period from 2000 to 2010, 499 (14 per cent) deaths were recorded.

Researchers at the BC-CfE developed and validated a new metric, the Programmatic Compliance Score (PCS), to assess the impact of non-compliance with HIV treatment guidelines on mortality among HIV-positive individuals on therapy within a fully subsidized antiretroviral therapy program. The PCS was based on the BC-CfE therapeutic guidelines, which are consistent with the International AIDS Society
-USA (IAS-USA) antiretroviral therapy management guidelines. The researchers hypothesized that non-compliance would be associated with the highest probability of premature death.

Based on the IAS-USA guidelines, the PCS is composed of six non-performance indicators: having less than three CD4 (immunity affected by HIV) count tests in the first year after starting antiretroviral therapy; having less than three plasma viral load  (viral replication) tests in the first year after starting antiretroviral therapy; no drug resistance testing prior to starting treatment; starting on a non-recommended antiretroviral therapy regimen; starting therapy with CD4 <200 cells/mm3; and not achieving HIV viral load suppression within six months since starting treatment. The sum of these six indicators was used to develop the PCS score with zero indicating full compliance and six indicating most non-compliance.

The study found that each PCS component was highly associated with mortality, even after adjusting for several important demographical and clinical factors.  However, individuals with a PCS score of four or higher were 22 times more likely to die than those with a PCS score of zero.

"The study results independently validate IAS-USA HIV therapeutic guidelines," said Dr. Julio Montaner, senior author of the study, director of the BC-CfE and head of the Division of AIDS in the Faculty of Medicine at the University of British Columbia. "The findings highlight the importance of adhering to treatment as per the guidelines, especially during the first year on HAART, to ensure that we can optimize the benefits derived from treatment as it relates to decreasing morbidity and mortality, and secondarily preventing new HIV infections."

The study only used information collected during the first year on therapy to predict the risk of mortality. The first year on antiretroviral therapy is very important in a patient's treatment history, as it often dictates the trajectory the disease will follow. This is particularly critical with regards to HIV, which has a great capacity to mutate into harder to treat variants when it is exposed to suboptimal regimens or if there is incomplete adherence to the treatment. 

"PCS is a simple and highly predictive metric of mortality among HIV-positive individuals who have started treatment for the first time," said Dr. Viviane Lima, lead author of the study and senior statistician at the BC-CfE. "These results provide valuable insights for health providers and administrative bodies in B.C. and internationally to develop strategies that will assist us to help patients adhere to treatment and improve health outcomes."

In British Columbia, the B.C.-pioneered Treatment as Prevention strategy has led to the widespread expansion of HAART coverage.  The BC-CfE has demonstrated that the benefits of early HAART treatment are twofold: it reduces the level of HIV in the blood to undetectable levels thus improving the health of people with HIV, and decreases the level of HIV in sexual fluids to undetectable levels thus reducing the likelihood of HIV transmission by more than 96 per cent.

Despite the undisputable benefits of HAART, it is still not clear which metrics, at the individual and the population levels, should be used to monitor and evaluate the impact of this powerful intervention. The PCS metric, developed by the BC-CfE, can prove an effective predictor of mortality and help better manage patients on treatment.  Further efforts are needed to enhance the PCS as a means to further improve clinical outcomes.