Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in Virologically Suppressed Individuals Enrolled in the SMART Study

Suboptimal (ie, <100%) antiretroviral therapy (ART) adherence has been associated with heightened inflammation in cohort studies, even among people with virologic suppression. We aimed to evaluate this association among participants in the Strategies for Management of Antiretroviral Therapy (SMART) study who had virologic suppression (HIV-1 VL < 200 copies/mL) at enrollment. Based on self-reported adherence (7-day recall), plasma concentrations of interleukin 6 and D-dimer were 9% (95% confidence interval [CI], 1%-18%; P = .02) and 11% (95% CI, 1%-22%; P = .03) higher in participants who reported suboptimal vs 100% adherence, respectively. These findings confirm previous observations and support the hypothesis that suboptimal ART adherence, even in the context of virologic suppression, may have significant biological consequences. ClinicalTrials.gov number NCT00027352

Incomplete ART adherence is associated with higher inflammation in individuals who achieved virologic suppression in the START study

INTRODUCTION: Suboptimal ART adherence, despite HIV viral suppression, has been associated with chronic residual inflammation. Whether this association extends to individuals who initiate ART during early HIV infection remains unknown, which was the objective of this study. METHODS: Plasma levels of interleukin‐6 (IL‐6), high‐sensitivity C‐reactive protein, serum amyloid A protein (SAA), IL‐27, soluble intercellular adhesion molecule‐1, soluble vascular adhesion molecule‐1, D‐dimer and the CD4+/CD8+ T‐cell ratio, were analysed at baseline and eight months after ART initiation in treatment‐naïve participants with HIV and CD4+ T‐cells >500 cells/mm^{3} enrolled in the immediate arm of START. Adherence was assessed by seven‐day self‐report. Multivariable linear regression was utilized to analyse the association between ART adherence and each biomarker at the eight‐month visit in participants who achieved virologic suppression (<50 copies/mL). RESULTS: We evaluated 1627 participants (422 female) who achieved virologic suppression at the eight‐month visit in the period between 2009 and 2013. Median (IQR) CD4+ T‐cell count before ART was 651 (585, 769) cells/mm^{3}. Incomplete adherence was reported in 109 (7%) participants at the eight month visit. After adjusting for covariates, plasma IL‐6 was 1.12 (95% CI, 1.00 to 1.26; p = 0.047) fold higher in participants reporting incomplete versus 100% adherence. A similar association for SAA was observed in an exploratory analysis (1.29 (95% CI 1.04 to 1.60); p = 0.02). No significant differences in other biomarkers were observed. CONCLUSIONS: Incomplete ART adherence was associated with higher IL‐6 levels in individuals who achieved virologic suppression early after ART initiation in START. A potential similar association for SAA requires confirmation. These findings suggest a role for identifying strategies to maximize ART adherence even during virologic suppression. ClinicalTrials.gov number: NCT00867048

Intrapatient variability of the hair levels of pain medications in chronic migraine patients - a pilot study

Monitoring of prescription pain medications is strongly recommended, considering their abuse liability. We used hair analysis for monitoring pain medications in 12 women with chronic migraine and drug overuse. Hair samples were collected at baseline and after 4 and 8 months and analyzed by liquid chromatography‐electrospray tandem mass spectrometry (LC‐MS/MS). Intrapatient variability of the hair level‐to‐dose ratio was &lt; 20% in most cases. The hair analysis detected changes in the dose taken by the same patient over time, both occasionally and chronically. The agreement between the changes in hair drug levels and those of taken doses was excellent. Therefore, hair analysis appeared advantageous for long‐term monitoring of pain medications, which is otherwise difficult to determine in conventional matrices. In the same sample, multiple medications could be simultaneously determined, and with three samples, nine months of therapy were objectively documented

Outcomes for efavirenz versus nevirapine-containing regimens for treatment of HIV-1 infection: a systematic review and meta-analysis.

INTRODUCTION: There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART). METHODS: We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR) and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I(2) statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds. RESULTS: Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73-0.99] I(2) = 0%) and observational studies (RR 0.65 [0.59-0.71] I(2) = 54%). EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00-1.08] I(2) = 0%) and observational studies (RR 1.06 [1.00-1.12] I(2) = 68%). CONCLUSION: EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings