Effect of directly observed therapy for highly active antiretroviral therapy on virologic, immunologic, and adherence outcomes: a meta-analysis and systematic review

Abstract

Introduction: Directly observed therapy of highly active antiretroviral therapy (DOT-HAART) is a feasible adherence intervention. Prospective DOT-HAART studies have shown mixed results, and optimal target groups have yet to be defined. We performed a meta-analysis and systematic review to assess the effect of DOT-HAART on adherence and virologic and immunologic response.

Methods: We performed a comprehensive search through August 2009 to identify peer-reviewed controlled studies that involved outpatient DOT-HAART among adults and reported at least 1 outcome assessed in this meta-analysis. Random-effects meta-analyses were performed; differences in effect on virologic suppression were examined using stratified meta-analyses and meta-regression on several study characteristics.

Results: Seventeen studies met inclusion criteria. Compared with control groups, DOT-HAART recipients were more likely to achieve an undetectable viral load (random effects risk ratio 1.24, 95% confidence interval (CI): 1.08 to 1.41), a greater increase in CD4 cell count (random effects weighted mean difference 43 cells/microL, 95% CI: 12 to 74 cells/microL), and HAART adherence of > or =95% (random effects risk ratio 1.17, 95% CI: 1.03 to 1.32). Results varied with respect to virologic response. DOT-HAART did not have a significant effect on virologic suppression when restricted to randomized controlled studies. Post-treatment effect was not observed in a limited number of studies.

Conclusions: DOT-HAART had a significant effect on virologic, immunologic, and adherence outcomes, although its efficacy was not supported when restricting analysis to randomized controlled trials. DOT-HAART shows greatest treatment effect when targeting individuals with greater risk of nonadherence and when delivering the intervention that maximizes participant convenience and provides enhanced adherence support. Further investigation is needed to assess the postintervention effect and cost-effectiveness of DOT-HAART.

FIGURE 1

Flow diagram of selection process for systematic review and meta-analysis. CRISP, Computer Retrieval of Information on Scientific Projects database; CROI, Conference on Retroviruses and Opportunistic Infections; IAS, International AIDS Society; NIMH/IAPAC, National Institute of Mental Health and the International Association of Physicians in AIDS Care International Conference on HIV Treatment Adherence.

FIGURE 2

Forest plot of studies with results on the effect of DOT-HAART on virologic suppression. Values shown are among data available. The size of the squares is proportional to the inverse variance of log-transformed RRs. The arrow indicates that the 95% CI has been truncated to limits of the x axis scale. n, the number of patients achieving virologic suppression; N, the total number of patients in the study arm; RE, random effects.

FIGURE 3

Durability of DOT-HAART. Postintervention change in effect of DOT-HAART on virologic suppression in studies that assessed durability of DOT-HAART.

FIGURE 4

Forest plot of studies with results on the effect of DOT-HAART on mean change in CD4 cell count. Values shown are among data available. The size of the squares is proportional to the inverse variance of mean differences. The arrow indicates that the 95% CI has been truncated to limits of the x axis scale.

FIGURE 5

Forest plot of studies with results on the effect of DOT-HAART on ≥95% adherence to prescribed doses. Values shown are among data available. The size of the squares is proportional to the inverse variance of log-transformed RRs. The arrow indicates that the 95% CI has been truncated to limits of the x axis scale. n, the number of patients achieving ≥95% adherence; N, the total number of patients in the study arm.