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

Adherence 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. We 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. In 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. These 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 effect

Self-reported adherence and pharmacy refill adherence are both predictive for an undetectable viral load among HIV-infected migrants receiving cART

HIV-infected migrants were shown to have poorer treatment outcomes than Dutch HIV-infected patients, often due to worse treatment adherence. Self-reported adherence would be an easy way to monitor adherence, but its validity relative to pharmacy refill adherence has not been extensively evaluated in migrants. All HIV-infected migrants older than 18 years and in care at the two Rotterdam HIV-treatment centers were eligible. Refill data with leftover medication (PRL) (residual pill count) were obtained from their pharmacies up to 15 months prior to inclusion. Self-reported adherence to combination Antiretroviral Therapy was assessed by four questions about adherence at inclusion. Additionally, risk factors for pharmacy refill non-adherence were examined. In total, 299 HIV-infected migrants were included. Viral load (VL) was detectable in 11% of the patients. Specificity of PRL was 53% for patients with an adherence of 100% and decreased with lower cut-off values. Sensitivity and negative predictive value (NPV) were 68% and 15% and increased with lower cut-off values. Positive predictive value (PPV) was around 93% for all cut-off values. Using the self-reported questions, 139 patients (47%) reported to be adherent. Sensitivity was 49% and specificity was 72%. PPV and NPV were 95% and 13%. No risk factors for pharmacy refill non-adherence were found in multivariable analyses. Both PRL and self-reported adherence, can predict undetectable VL in HIV-infected migrants. PPV and NPV are similar for both methods. This study shows that using four self-reported items is sufficient to predict adherence which is crucial for optimal clinical outcome in HIV-infected migrants

Perceptions of HIV cure and willingness to participate in HIV cure-related trials among people enrolled in the Netherlands cohort study on acute HIV infection

BACKGROUND: People who initiate antiretroviral therapy (ART) during acute HIV infection are potential candidates for HIV cure-related clinical trials, as early ART reduces the size of the HIV reservoir. These trials, which may include ART interruption (ATI), might involve potential risks. We explored knowledge and perception of HIV cure and willingness to participate in cure-related trials among participants of the Netherlands Cohort Study on Acute HIV infection (NOVA study), who started antiretroviral therapy immediately after diagnosis of acute HIV infection. METHODS: We conducted 20 in-depth qualitative interviews with NOVA study participants between October–December 2018. Data were analyzed thematically, using inductive and iterative coding techniques. FINDINGS: Most participants had limited knowledge of HIV cure and understood HIV cure as complete eradication of HIV from their bodies. HIV cure was considered important to most participants, mostly due to the stigma surrounding HIV. More than half would consider undergoing brief ATI during trial participation, but only one person considered extended ATI. Viral rebound and increased infectiousness during ATI were perceived as large concerns. Participants remained hopeful of being cured during trial participation, even though they were informed that no personal medical benefit was to be expected. INTERPRETATION: Our results highlight the need for thorough informed consent procedures with assessment of comprehension and exploration of personal motives prior to enrollment in cure-related trials. Researchers might need to moderate their expectations about how many participants will enroll in a trial with extended ATI

Risk factors for non-adherence to cART in immigrants with HIV living in the Netherlands: Results from the Rotterdam ADherence (ROAD) project

In the Netherlands, immigrant people living with HIV (PLWH) have poorer psychological and treatment outcomes than Dutch PLWH. This cross-sectional field study examined risk factors for non-adherence to combination Antiretroviral Therapy (cART) among immigrant PLWH. First and second generation immigrant PLWH attending outpatient clinics at two HIV-treatment centers in Rotterdam were selected for this study. Socio-demographic and clinical characteristics for all eligible participants were collected from an existing database. Trained interviewers subsequently completed questionnaires together with consenting participants (n = 352) to gather additional data on socio-demographic characteristics, psychosocial variables, and self-reported adherence to cART. Univariable and multivariable logistic regression analyses were conducted among 301 participants who had used cART 6 months prior to inclusion. Independent risk factors for self-reported non-adherence were (I) not having attended formal education or only primary school (OR = 3.25; 95%CI: 1.28-8.26, versus University), (II) experiencing low levels of social support (OR = 2.56; 95%CI: 1.37-4.82), and (III) reporting low treatment adherence self-efficacy (OR = 2.99; 95%CI: 1.59-5.64). Additionally, HIV-RNA >50 copies/ml and internalized HIV-related stigma were marginally associated (P<0.10) with non-adherence (OR = 2.53; 95%CI: 0.91-7.06 and OR = 1.82; 95%CI: 0.97-3.43). The findings that low educational attainment, lack of social support, and low treatment adherence self-efficacy are associated with non-adherence point to the need for tailored supportive interventions. Establishing contact with peer immigrant PLWH who serve as role models might be a successful intervention for this specific population

Long-term MRA follow-up after coiling of intracranial aneurysms: impact on mood and anxiety

Magnetic resonance angiography (MRA) screening for recurrence of a coiled intracranial aneurysm and formation of new aneurysms long-term after coiling may induce anxiety and depression. In coiled patients, we evaluated effects on mood and level of anxiety from long-term follow-up MRA in comparison to general population norms. Of 162 patients participating in a long-term (> 4.5 years) MRA follow-up after coiling, 120 completed the EQ-5D questionnaire, a visual analog health scale and a self-developed screening related questionnaire at the time of MRA. Three months later, the same questionnaires were completed by 100 of these 120 patients. Results were compared to general population norms adjusted for gender and age. Any problem with anxiety or depression was reported in 56 of 120 patients (47%; 95%CI38a dagger"56%) at baseline and 42 of 100 patients (42%; 95%CI32a dagger"52%) at 3 months, equally for screen-positives and -negatives. Compared to the reference population, participants scored 38% (95%CI9a dagger"67%) and 27% (95%CI4a dagger"50%) more often any problem with anxiety or depression. Three months after screening, 21% (20 of 92) of screen-negatives and 13% (one of eight) of screen-positives reported to be less afraid of subarachnoid hemorrhage (SAH) compared to before screening. One of eight screen-positives reported increased fear of SAH. Patients with coiled intracranial aneurysms participating in long-term MRA screening reported significantly more often to be anxious or depressed than a reference group. Screening did not significantly increase anxiety or depression temporarily. However, subjectively, patients did report an increase in anxiety caused by screening, which decreased after 3 months

Adherence to preventive measures after SARS-CoV-2 vaccination and after awareness of antibody response in kidney transplant recipients in the Netherlands:a nationwide questionnaire study

BACKGROUND: Kidney transplant recipients (KTRs) were advised to tightly adhere to government recommendations to curb the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) because of a high risk of morbidity and mortality and decreased immunogenicity after vaccination. The aim of this study was to analyse the change in adherence to preventive measures after vaccination and awareness of antibody response, and to evaluate its effectiveness.METHODS: In this large-scale, national questionnaire study, questionnaires were sent to 3531 KTRs enrolled in the Dutch RECOVAC studies, retrospectively asking for adherence to nine preventive measures on a 5-point Likert scale before and after SARS-CoV-2 vaccination and after awareness of antibody response. Blood samples were collected 28 days after the second vaccination. Antibody response was categorised as non-responder (≤50 BAU/mL), low-responder (&gt;50 ≤ 300 BAU/mL) or high-responder (&gt;300 BAU/mL), and shared with participants as a correlate of protection. Participants of whom demographics on sex and age, blood samples and completed questionnaires were available, were included. Our study took place between February 2021 and January 2022. The primary outcome of adherence before and after vaccination was assessed between August and October 2021 and compared via the Wilcoxon signed rank sum test. Logistic regression analysis was performed to estimate the association between antibody response and non-adherence, and adherence on acquiring SARS-CoV-2 infection. This study is registered at ClinicalTrials.gov (NCT04841785).FINDINGS: In 2939 KTRs (83%) who completed the first questionnaire on adherence to preventive measures, adherence was higher before than after vaccination (4.56, IQR 4.11-4.78 and 4.22, IQR 3.67-4.67, p &lt; 0.001). Adherence after awareness of antibody response was analysed in 2399 KTRs (82%) of whom also blood samples were available, containing 949 non-responders, 500 low-responders and 950 high-responders. Compared to non-responders, low- and high-responders reported higher non-adherence. Higher adherence was associated with lower infection rates before and after vaccination (OR 0.67 [0.51-0.91], p = 0.008 and OR 0.48 [0.28-0.86], p = 0.010).INTERPRETATION: Adherence decreased after SARS-CoV-2 vaccination and in KTRs who were aware of a subsequent antibody response compared with those without. Preventive measures in this vulnerable group seem to be effective, regardless of vaccination status. This study starts a debate on sharing antibody results with the patient and future studies should elucidate whether decreased adherence in antibody responders is justified, also in view of future pandemics.FUNDING: The Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation.</p

Self-reported adherence to antiretroviral therapy for HIV-1 infection and virologic treatment response - A meta-analysis

Background: Adherence to highly active antiretroviral therapy (HAART) for HIV-1 infection is essential for plasma HIV-1 RNA suppression. Self-report is the most frequently used measure of adherence to HAART, but its validity is controversial. Studies on the relation between self-reported adherence and virologic treatment response have shown inconsistent results. We investigated whether this variability between studies about the effect of self-reported adherence on virologic treatment response could be attributed to study design features. Methods: We searched for studies reporting on adult nonpregnant patients prescribed antiretroviral therapy for chronic HIV-1 infection using a self-reported adherence measure and providing information about the relation between adherence and plasma HIV-1 RNA concentrations. Meta-analysis with random effects modeling was used to pool data and to investigate sources of heterogeneity. Results: Sixty-five studies fulfilled inclusion criteria, containing data from 15,351 patients. The pooled odds ratio (95% confidence interval) of detectable plasma viral load in nonadherent patients was 2.31 (1.99-2.68). There was significant heterogeneity among studies (P <0.001). Not ascertaining confidentiality of responses, use of actual viral load measurements, an adherence threshold lower than 95%, higher percentages of patients on their initial antiretroviral regimen, and higher percentages of patients with a history of intravenous drug use within a study were associated with higher point estimates. Conclusions: Overall, we observed that self-reported adherence measures can distinguish between clinically meaningful patterns of medication-taking behavior. Distinct study characteristics were significantly associated with the relation between adherence and virologic response. These characteristics should be taken into consideration when interpreting results from studies on self-reported adherenc