Nienke Langebeek

Predictors and correlates of adherence to combination antiretroviral therapy (ART) for chronic HIV infection: a meta-analysis

BackgroundAdherence to combination antiretroviral therapy (ART) is a key predictor of the success of human immunodeficiency virus (HIV) treatment, and is potentially amenable to intervention. Insight into predictors or correlates of non-adherence to ART may help guide targets for the development of adherence-enhancing interventions. Our objective was to review evidence on predictors/correlates of adherence to ART, and to aggregate findings into quantitative estimates of their impact on adherence.MethodsWe searched PubMed for original English-language papers, published between 1996 and June 2014, and the reference lists of all relevant articles found. Studies reporting on predictors/correlates of adherence of adults prescribed ART for chronic HIV infection were included without restriction to adherence assessment method, study design or geographical location. Two researchers independently extracted the data from the same papers. Random effects models with inverse variance weights were used to aggregate findings into pooled effects estimates with 95% confidence intervals. The standardized mean difference (SMD) was used as the common effect size. The impact of study design features (adherence assessment method, study design, and the United Nations Human Development Index (HDI) of the country in which the study was set) was investigated using categorical mixed effects meta-regression.ResultsIn total, 207 studies were included. The following predictors/correlates were most strongly associated with adherence: adherence self-efficacy (SMD = 0.603, P = 0.001), current substance use (SMD = -0.395, P = 0.001), concerns about ART (SMD = -0.388, P = 0.001), beliefs about the necessity/utility of ART (SMD = 0.357, P = 0.001), trust/satisfaction with the HIV care provider (SMD = 0.377, P = 0.001), depressive symptoms (SMD = -0.305, P = 0.001), stigma about HIV (SMD = -0.282, P = 0.001), and social support (SMD = 0.237, P = 0.001). Smaller but significant associations were observed for the following being prescribed a protease inhibitor-containing regimen (SMD = -0.196, P = 0.001), daily dosing frequency (SMD = -0.193, P = 0.001), financial constraints (SMD -0.187, P = 0.001) and pill burden (SMD = -0.124, P = 0.001). Higher trust/satisfaction with the HIV care provider, a lower daily dosing frequency, and fewer depressive symptoms were more strongly related with higher adherence in low and medium HDI countries than in high HDI countries.ConclusionsThese findings suggest that adherence-enhancing interventions should particularly target psychological factors such as self-efficacy and concerns/beliefs about the efficacy and safety of ART. Moreover, these findings suggest that simplification of regimens might have smaller but significant effects.

Abacavir/Lamivudine/Zidovudine Maintenance After Standard Induction in Antiretroviral Therapy-Naive Patients: FREE Randomized Trial Interim Results

Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4 <or=350 cells/mm(3) and HIV-1 RNA concentrations (viral load [VL]) greater than 30,000 copies per milliliter. Patients were randomized after reaching VL less than 50 copies per milliliter on two consecutive occasions between 12 and 24 weeks after start of zidovudine/lamuvidine and lopinavir/ritonavir combination. Eligible subjects switched to abacavir/lamivudine/zidovudine (TZV) or continued the PI-containing regimen. Here we present the 48-week data with virologic success rate (failure: VL > 50 copies per milliliter). Two hundred seven patients had similar baseline (BL) characteristics: median CD4 180 cells/mm(3), median VL 5.19 log(10) copies per milliliter. One hundred twenty subjects (58%) met randomization criteria. Baseline VL differed significantly between dropouts and randomized subjects (median 5.41 versus 5.06 log(10) copies per milliliter, p = 0.017), as did CD4 cells (median 160 and 200 cells/mm(3), p = 0.044). Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI. At week 48, 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression (log rank test; p = 0.379). CD4 counts increased significantly in both arms. In ART-naïve patients, TZV maintenance had similar antiviral efficacy compared to continued standard ART at 48 weeks after baseline. Patients on successful standard ART can be safely switched to a NRTI-only regimen, at least for the tested time period.

Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance

OBJECTIVES In ∼10% of newly diagnosed HIV-1 patients, drug-resistant viral variants are detected. In such transmitted HIV-1 variants, the thymidine analogue mutation (TAM) M41L is frequently observed as a single resistance mutation and these viral variants often belong to phylogenetic transmission clusters. The presence of at least three TAMs, in particular patterns with M41L/L210W, impairs the efficacy of the extensively used drug tenofovir. We investigated whether the presence of a single M41L mutation at baseline influences the selection of resistance to tenofovir and emtricitabine in vitro and in vivo. METHODS The impact of M41L on the development of drug resistance to tenofovir and emtricitabine was determined by extensive in vitro selection experiments and investigation of the virological outcome of patients on a first-line regimen. RESULTS The presence of a single M41L mutation did not influence the selected mutational profile or the genetic barrier to resistance to tenofovir and/or emtricitabine during long-term in vitro selection experiments. In vivo, virological outcome of first-line regimens containing tenofovir and emtricitabine was comparable between patients diagnosed with HIV-1 harbouring M41L (n=17, 16 were part of one transmission cluster) and WT virus (n=248). CONCLUSIONS Detection of a single M41L reverse transcriptase mutation at baseline did not influence the development of resistance in vitro or virological outcome on tenofovir-containing regimens in patients belonging to a large transmission cluster. Our results indicate that a high genetic barrier regimen may not be required when patients are diagnosed with HIV variants containing a single M41L mutation in reverse transcriptase.

Impact of comorbidity and ageing on health-related quality of life in Hiv-positive and Hiv-negative individuals

Background: HIV-infected individuals may be at risk for the premature onset of age-associated noncommunicable comorbidities. Being HIV-positive, having comorbidities and being of higher age may adversely impact health-related quality of life (HRQL). We investigated the possible contribution of HIV infection, comorbidities and age on HRQL and depression. Methods: HIV-infected individuals and uninfected controls from the AGEhIV Cohort Study were screened for the presence of comorbidities. They completed the Short Form 36-item Health Survey to assess HRQL and the nine-item Patient Health Questionnaire to assess depression. Linear and logistic regression were used to investigate to which extent comorbidities, aging and HIV infection were independently associated with HRQL and depression. Results: HIV-infected individuals (n = 541) reported significantly worse physical and mental HRQL and had a higher prevalence of depression than HIV-uninfected individuals (n = 526). A higher number of comorbidities and HIV-positive status were each independently associated with worse physical HRQL, whereas HIV-positive status and younger age were independently associated with worse mental HRQL and more depression. The difference in physical HRQL between HIV-positive and HIV-negative individuals did not become greater with a higher number of comorbidities or with higher age. Conclusion: In a cohort of largely well suppressed HIV-positive participants and HIV-negative controls, HIV-positive status was significantly and independently associated with worse physical and mental HRQL and with an increased likelihood of depression. Our finding that a higher number of comorbidities was independently associated with worse physical HRQL reinforces the importance to optimize prevention and management of comorbidities as the HIV-infected population continues to age.BACKGROUND HIV-infected individuals may be at risk for the premature onset of age-associated non-communicable co-morbidities. Being HIV-positive, having comorbidities and being of higher age may adversely impact health-related quality of life (HRQL). We investigated the possible contribution of HIV infection, co-morbidities, and age on HRQL and depression. METHODS HIV-infected individuals and uninfected controls from the AGEhIV Cohort Study were screened for the presence of co-morbidities. They completed the Short Form 36-item Health Survey to assess HRQL and the nine-item Patient Health Questionnaire to assess depression. Linear and logistic regression were used to investigate to which extent co-morbidities, aging and HIV infection were independently associated with HRQL and depression. RESULTS HIV-infected individuals (n = 541) reported significantly worse physical and mental HRQL and had a higher prevalence of depression than HIV-uninfected individuals (n = 526). A higher number of co-morbidities and HIV-positive status were each independently associated with worse physical HRQL, whereas HIV-positive status and younger age were independently associated with worse mental HRQL and more depression. The difference in physical HRQL between HIV-positive and HIV-negative individuals did not become greater with a higher number of co-morbidities or with higher age. CONCLUSIONS In a cohort of largely well-suppressed HIV-positive participants and HIV-negative controls, HIV-positive status was significantly and independently associated with worse physical and mental HRQL and with an increased likelihood of depression. Our finding that a higher number of co-morbidities was independently associated with worse physical HRQL reinforces the importance to optimize prevention and management of co-morbidities as the HIV-infected population continues to age.

Electronic Medication Monitoring-Informed Counseling to Improve Adherence to Combination Anti-Retroviral Therapy and Virologic Treatment Outcomes: A Meta-Analysis

Background Adherence to combination anti-retroviral therapy for HIV infection is a primary determinant of treatment success, but is often suboptimal. Previous studies have suggested that electronic medication monitoring-informed counseling is among the most effective adherence intervention components. Our objective was to review available evidence about the effectiveness of monitoring-informed counseling and to aggregate findings into quantitative estimates of the effect of such intervention on medication adherence and virologic treatment outcomes. Methods We searched PubMed for papers reporting on randomized controlled trials comparing intervention groups receiving monitoring-informed counseling as one of the intervention components versus control groups not receiving such counseling for their effect on medication adherence and viral load concentrations. The standardized mean difference (SMD) in adherence and the odds ratio (OR) of undetectable HIV RNA in intervention versus control groups were the common effect sizes. Random-effect models with inverse variance weights were used to aggregate findings into pooled effect estimates with 95% confidence limits (CI). Results A total of 13 studies were included. Adherence was significantly higher in intervention groups than in control groups (SMD 0.51, 95% CI 0.31–0.71). Patients in intervention groups were significantly more likely to have undetectable HIV RNA concentrations than patients in control groups (OR 1.35, 95% CI 1.12–1.63). However, in studies in which monitoring-informed counseling was the only intervention component, the difference in adherence and virologic response between intervention and control groups was not statistically significant. Conclusion Electronic monitoring-informed counseling improved adherence and virologic response compared with control groups not receiving such counseling in studies in which it was one out of multiple intervention components, but not in studies where it was the only intervention component.

A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96-week results from the FREE study

The aim of the study was to test the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen, with potential beneficial metabolic effects, as maintenance therapy after induction with dual NRTIs and a boosted protease inhibitor (PI).

A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy

The aim of the study was to test the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen, with potential beneficial metabolic effects, as maintenance therapy after induction with dual NRTIs and a boosted protease inhibitor (PI).

A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96-week results from the FREE study: Single-class NRTI maintenance ART

The aim of the study was to test the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen, with potential beneficial metabolic effects, as maintenance therapy after induction with dual NRTIs and a boosted protease inhibitor (PI).