Therapeutic drug monitoring of antiretroviral drugs in HIV-infected patients

Introduction: Therapeutic drug monitoring (TDM) may be beneficial when applied to antiretroviral (ARV). Even though TDM can be a valuable strategy in HIV management, its role remains controversial.

Areas covered: This review provides a comprehensive update on important issues relating to TDM of ARV drugs in HIV-infected patients. Articles from PubMed with keywords relevant to each topic section were reviewed. Search strategies limited to articles published in English.

Expert commentary: There is evidence supporting the use of TDM in HIV treatment. However, some limitations need to be considered. The evidence supporting the use of routine TDM for all patients is limited, as it is not clear that this strategy offers any advantages over TDM for selected indications. Selected groups of patients including patients with physiological changes, patients with drug-drug interactions or toxicity, and the elderly could potentially benefit from TDM, as optimized dosing is challenging in these populations.     

Acceptability and satisfaction towards self‐collection for chlamydia and gonorrhoea testing among transgender women in Tangerine Clinic,Thailand: shifting towards the new normal

IntroductionProvider‐collected swabs are an unappealing procedure for many transgender women and may have led to suboptimal rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing. Self‐collection for CT/NG testing is recommended for men who have sex with men. However, the information on acceptability and clinical performance to support a recommendation for transgender women is lacking. We aimed to determine the acceptability and satisfaction towards self‐collection for CT/NG testing among Thai transgender women.MethodsThai transgender women who attended Tangerine Clinic (a transgender‐led, integrated, gender‐affirming care and sexual health services clinic in Bangkok, Thailand) between May and July 2020 and had condomless sexual intercourse within the past six months were offered to collect urine and perform self‐swabs of pharyngeal, rectal, and if applicable, neovaginal compartments for pooled nucleic acid amplification testing for CT/NG infections. Participants received a diagram, video and oral instructions about how to perform self‐collection procedure. Those who accepted self‐collection were also offered to receive provider collection to evaluate the performance between the two methods. Self‐administered questionnaires were used to assess satisfaction.ResultsAmong 216 transgender women enrolled, 142 (65.7%) accepted self‐collection. All who accepted had pharyngeal, rectal and urine samples collected. Of 31 transgender women who had undergone genital surgery, 28 (90.3%) accepted neovaginal self‐swab. The acceptance rate increased from 46.2% in May to 84.5% in July 2020. One participant had an invalid result. All transgender women who accepted self‐collection could perform it without assistance, and 82.8% were highly satisfied with the method. None reported dissatisfaction. Due to the COVID‐19 pandemic, provider collection services were discontinued early, and only eight transgender women were able to perform both methods for performance evaluation. The performance agreement was 100%.ConclusionsThai transgender women had high acceptability and satisfaction towards self‐collection for CT/NG testing. The performance was promising compared to provider collection. Our results support the implementation of self‐collection to the sexually transmitted infection services, particularly during the COVID‐19 pandemic where physical distancing is the new normal. A larger study is warranted to determine the performance of self‐collection for CT/NG testing in each anatomical compartment and confirm the performance between self‐collection and provider collection.     

Influence of ABCC2 and ABCC4 Polymorphisms on Tenofovir Plasma Concentrations in Thai HIV-Infected Patients

Tenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded by ABCC2 and ABCC4, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged ≥18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms of ABCC2 and ABCC4. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ± 7.2 years. The mean tenofovir plasma concentration was 100.3 ± 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and the ABCC4 4131T → G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having the ABCC4 4131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01138241","term_id":"NCT01138241"}}NCT01138241.)