Feasibility of Four Interventions to Improve Treatment Adherence in Migrants Living with HIV in The Netherlands.

We evaluated the feasibility and efficacy of four existing interventions to improve adherence to them in migrants living with HIV (MLWH): directly administered antiretroviral therapy (DAART), group medical appointments (GMA), early detection and treatment of psychological distress, and peer support by trained MLWH. At baseline and after the interventions, socio-demographic characteristics, psychosocial variables, and data on HIV treatment adherence were collected. The two questionnaires were completed by 234/301 (78%) MLWH included at baseline. Detectable HIV RNA decreased (from 10.3 to 6.8%) as did internalized HIV-related stigma (from 15 to 14 points), and self-reported adherence increased (between 5.5 and 8.3%). DAART and GMA were not feasible interventions. Screening of psychological distress was feasible; however, follow-up diagnostic screening and linkage to psychiatric services were not. Peer support for and by MLWH was feasible. Within this small intervention group, results on HIV RNA < 400 copies/mL (decrease of 23.6%) and outpatient clinic attendance (up to 20.4% kept more appointments) were promising.

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.

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.

Immunological analysis of treatment interruption after early highly active antiretroviral therapy.

We longitudinally evaluated HIV-specific T-cell immunity after discontinuation of highly active antiretroviral therapy (HAART). After treatment interruption (TI), some individuals could maintain a low plasma viral load (<15,000 copies/mL), whereas others could not (>50,000 copies/mL). Before HAART was initiated, plasma viral load was similar. After TI, the numbers of CD8(+) T cells increased more in individuals without viral control, whereas individuals maintaining a low viral load showed a more pronounced increase in HIV-specific CD8(+) T-cell numbers. No differences were seen in the number or percentage of cytokine-producing HIV-1-specific CD4(+) T cells, or in proliferative capacity of T cells. Four weeks after TI, the magnitude of the total HIV-1-specific CD8(+) T-cell response (IFN-γ(+) and/or IL-2(+) and/or CD107a(+)) was significantly higher in individuals maintaining viral control. Degranulation contributed more to the overall CD8(+) T-cell response than cytokine production. Whether increased T-cell functionality is a cause or consequence of low viral load remains to be elucidated.

Effects of active treatment discontinuation in patients with a CD4+ T-cell nadir greater than 350 cells/mm3: 48-week Treatment Interruption in Early Starters Netherlands Study (TRIESTAN).

OBJECTIVE: To evaluate the safety and efficacy of discontinuing highly active antiretroviral therapy (HAART) in HIV-1-positive patients who initiated HAART at a CD4+ T-cell count >350 cells/mm. METHODS: Eligible patients were identified from the Dutch AIDS Therapy Evaluation, The Netherlands (ATHENA) national observational cohort. Interruption or continuation of HAART was offered to all. RESULTS: Of 71 patients enrolled, 46 (64%) interrupted HAART (STOP group) and 25 (36%) continued HAART (control group). The median CD4+ T-cell nadirs at the start of HAART were 469 (interquartile range [IQR]: 430-720) cells/mm3 and 510 (IQR: 440-637) cells/mm3, respectively. At week 48, the median plasma HIV RNA level in the STOP group had stabilized at approximately pre-HAART values (4.55 log10, IQR: 4.2-4.9 copies/mL), but the CD4+ T-cell count still exceeded the pre-HAART count (563 cells/mm3, IQR: 450-710 cells/mm3). Only 5 patients (11%) had reinitiated HAART after 48 weeks, all for personal reasons. No Centers for Disease Control and Prevention category events or death occurred after interruption. In 6 (13%) of 46 patients, mild symptoms of acute retroviral rebound syndrome (ARVS) were identified. No improvement was observed in mental or physical health scores. In 37% of patients, nonnucleoside reverse transcriptase inhibitor drug concentrations were still detectable 1 week after stopping. CONCLUSIONS: Although HAART can safely be interrupted in patients with a high CD4 T-cell nadir, no improvement in quality of life was established. Patients can experience ARVS, the risk for development of resistance after treatment interruption is realistic, and there is a potential hazard of HIV transmission to sexual partners. We would not actively advise stopping treatment in patients who started treatment too early according to current guidelines.