Previous poor adherence and HCV are risk factors for antiretroviral treatment failure

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Over a quarter of patients taking antiretroviral therapy at a leading US treatment centre experienced treatment failure, a study published in the January 1st edition of the Journal of Acquired Immune Deficiency Syndromes has found. The investigators, from the Massachusetts General Hospital also found that 18% of patients experienced treatment failure because of a rebound in viral load. Unsurprisingly, poor adherence was identified as a risk factor for treatment failure, but unlike some earlier studies, the investigators found that it was possible to predict which patients were likely to be non-adherent. Another surprising finding of the study was that coinfection with hepatitis C virus was a risk factor for the virological failure of HIV therapy.

Antiretroviral therapy performs poorer in a clinical setting than in clinical trials. Doctors at the Massachusetts General Hospital and Harvard Medical School wished to see if they could predict the factors associated with treatment failure in a large population of HIV-positive individuals with varied demographic characteristics and treatment histories. A retrospective, longitudinal study was therefore designed including 829 patients taking any antiretroviral regimen who had achieved a viral load below 400 copies/ml in a two-year period between early 2003 and late 2004.

Treatment failure was defined as loss to follow-up; stopping antiretroviral therapy without the prior agreement of the treating physician; or, a rebound in viral load above 400 copies/ml.

Glossary

treatment failure

Inability of a medical therapy to achieve the desired results. 

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

longitudinal study

A study in which information is collected on people over several weeks, months or years. People may be followed forward in time (a prospective study), or information may be collected on past events (a retrospective study).

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

Data were gathered on the patients’ baseline demographic characteristics, previous antiretroviral treatment history, adherence to earlier HIV treatment regimens and hepatitis C virus infection status.

Of the 829 patients included in the investigators initial analysis, approximately 75% (614) achieved at least one viral load below 400 copies/ml during the period of the study. Of these patients, 167 were defined as experiencing treatment failure, and of these 108 individuals were defined as experiencing virological failure.

In multivariate analysis, the investigators found that poor adherence (p 3 (p = 0.013), a detectable viral load at the start of the study period (p 3. Coinfection with hepatitis C virus was of borderline significance (p = 0.059).

The investigators then turned their attention to the factors associated with virological failure. They found that poor adherence (p 3, a baseline CD4 cell count below 200 cells/mm3, and coinfection with hepatitis C virus (p = 0.028) all predicted virological failure.

Taking a regimen that was composed of NRTIs and an NNRTI was, however, protective against virological failure (p = 0.05).

Unsurprisingly, adherence was a risk factor for treatment failure. But the investigators were able to predict which patients would be non-adherent and experience treatment failure. At baseline, 58 patients (9% of the cohort) were categorised as being poorly adherent. Of these individuals, 40 (69%) developed treatment failure, accounting for a quarter of all treatment failure. Patients defined as having poor adherence on entry to the study, were significantly more likely to experience treatment failure than patients with good adherence (p

References

Robbins GK et al. Predictors of antiretroviral treatment failure in an urban HIV clinic. J Acquir Immune Defic Syndr 44: 30 – 37, 2007.