Addressing Adherence

Top 3 Reasons for Virologic Failure

1. Medication Nonadherence

Medication nonadherence is the leading cause of viral resistance, as described below. In some situations, however, virologic failure may occur without resistance, if youth are taking so few of their ARVs that no selective pressure is exerted on the HIV.

2. Inadequate Drug Levels

When a youth who is taking ARVs does not have adequate suppression of HIV viral load, providers should first determine whether the medication dosages are adequate.

• Subtherapeutic drug levels may occur because of inadequate adherence with the ARV regimen; this is the most common reason for virologic failure.
• As youth grow, their dosage requirements may increase; ARV doses may not be adjusted adequately.
• Numerous drug-drug interactions must be assessed carefully (eg, tenofovir can reduce drug concentrations of unboosted atazanavir to subtherapeutic levels).
• Diarrheal illness can adversely affect drug absorption.
• Poor drug absorption may occur if atazanavir is given with acid-blocking medications. It also may occur more frequently with other ARVs that require food for absorption, as youth often do not follow the food-requiring instructions because of busy lifestyles or irregular schedules.

3. Resistance to ARVs

Youth for whom ART regimens are failing may harbor HIV that is resistant to one or more of their medications. They may have been infected with a resistant virus; in one study, 20% of newly infected youth had HIV that had at least one significant resistance mutation.9 IHowever, the most common reason for the development of new resistance is inadequate adherence to ART, with the emergence of resistance in the setting of inadequate drug levels.

When a patient does not take medications regularly and at appropriate dosages, viral replication occurs in the presence of subtherapeutic drug levels. This leads to selective pressure for the virus to mutate and become resistant to the medications currently being used. Even worse, some viral mutations can lead to cross-resistance to other antiretroviral agents. Once a mutation occurs in the HIV virus within an individual, most experts believe it will remain there forever.

Inadequate adherence can take various forms. Youth may not take any of their medications, may avoid a single medication they see as having bad side effects, or may randomly or predictably skip doses of the regimen. Partial viral suppression commonly leads to further viral resistance and greater increases in viral load over time.

References

9. Viani RM, Peralta L, Aldrovandi G, et al. Adolescent Medicine Trials Network for HIV/AIDS Interventions. Prevalence of primary HIV-1 drug resistance among recently infected adolescents: a multicenter adolescent medicine trials network for HIV/AIDS interventions study. J Infect Dis. 2006 Dec 1;194(11):1505-9.