Pharmacodynamics of efavirenz 400 mg in treatment-naïve Chinese HIV-infected patients in a prospective cohort study.

BACKGROUND: The plasma concentration of patients treated with efavirenz (EFV) 600 mg was found to exceed the upper limit of the proposed therapeutic window in most Chinese HIV-infected individuals; thus, dosage reduction of EFV to 400 mg daily warranted consideration. This study aimed to assess the pharmacodynamics of EFV 400 mg for HIV-1-infected patients in China. METHOD: Twenty cART-naïve individuals were enrolled in this study. EFV 400 mg combined with tenofovir (TDF) and lamivudine (3TC) as an initial antiretroviral regimen was administered for 48 weeks. EFV concentration and T cell subsets as well as HIV RNA load were evaluated at baseline and at 4, 12, 24, and 48 weeks. Moreover, neuropsychiatric adverse effects were also assessed by the Hamilton depression (HAMD) scale and Pittsburgh sleep quality index (PSQI). RESULTS: Eighteen males and two females whose median age was 26 (interquartile range [IQR]: 23-32) years completed 48 weeks of follow-up. The median EFV concentrations were 1.88 (IQR: 1.54-2.42), 1.74 (IQR: 1.36-1.93), 1.93 (IQR: 1.66-2.22), and 1.85 (IQR: 1.54-2.14) mg/L at weeks 4, 12, 24, and 48, respectively. The viral load was 4.59 (IQR: 4.10-5.19) log10 copies/mL at baseline, and it decreased by 4.6 (IQR: 3.98-5.18) log10 copies/mL from baseline to week 48. Three of 20 (15%), 10 of 20 (50.0%), 17 of 20 (85%), and 18 of 19 (95%) participants had a plasma viral load less than 50 copies/mL at weeks 4, 12, 24, and 48, respectively. The median CD4 cell count was 330 (IQR: 237-410) cells/µL at baseline, and it increased to 473 (IQR: 344-574) cells/µL at 48 weeks. The HAMD score was 5 (IQR: 3-9.8) and 3 (IQR: 2.25-4) at baseline and 48 weeks, respectively. The PSQI score was 4 (IQR: 2-5.8) and 3 (IQR: 2-4) at baseline and 48 weeks, respectively. Dizziness was the most common event, occurring in 70% of patients within the first 2 weeks of treatment. CONCLUSION: Patients prescribed with EFV 400 mg-containing agents demonstrated favourable virological and immunological responses. And the plasma EFV concentration was within the recommended therapeutic range, with fewer adverse reactions than with EFV 600 mg. EFV 400 mg was effective and safe in Chinese HIV-infected patients. TRIAL REGISTRATION: NCT04596488 ; Registered 21 October, 2020; Retrospectively registered.

Feasibility of using dried blood spots for HIV viral load testing among HIV-infected individuals in Thailand using QIAGEN QIAsymphony-artus HIV-1 platform.

In settings where plasma preparation and sample centralization are not feasible or inconvenient, dried blood spots (DBS) could be used as an alternative specimen to plasma to assess antiretroviral treatment response among HIV-infected individuals. This study was aimed to (1) validate the recent QIAsymphony-artus assay for DBS HIV viral load (VL) and (2) assess the feasibility of measuring HIV VL on DBS using this assay in Thailand. Ethylenediaminetetraacetic acid-blood samples from 99 HIV-infected individuals were used to prepare paired DBS and plasma. Also, DBS samples were shipped to three distant hospitals in the northern region. After short-term storage, DBS were returned by regular post to the AMS laboratory and were re-tested for HIV VL using the same platform. HIV VL results were compared using Pearson's correlation and Bland-Altman analysis. DBS HIV VL fairly correlated to plasma HIV VL (R = 0.62) with a mean difference of 0.02 log10 IU/mL (SD = 1.06). A high correlation (R = 0.79) was observed between HIV VL in DBS before and after shipping (mean difference = 0.14 log10 IU/mL, SD = 0.74), indicating good stability of HIV RNA in DBS. DBS can be used as an alternative specimen for HIV VL monitoring in Thailand. However, measurement of HIV VL with the QIAGEN QIAsymphony-artus assay should be improved, especially the DBS pre-extraction process.

Associations of gender and serum total cholesterol with CD4+ T cell count and HIV RNA load in antiretroviral-naïve individuals in Addis Ababa.

BACKGROUND: Males are more susceptible than females to infections due to the differences in endocrine-immune interactions. Furthermore, it is reported that lowering cell cholesterol impairs viral replication and infection in vitro. However, the production of oxysterols in vivo by oxidation of cholesterol may result in inhibition of HIV replication. Therefore, this study was designed to determine the associations of gender and serum total cholesterol with CD4+ T cell counts and/or WHO clinical stages, and HIV ribonucleic acid (RNA) load in antiretroviral therapy (ART) naive study population with known sero-positive time of stay in Addis Ababa.  METHODS: A cross-sectional study was conducted from February to August 2013 on 594 HIV-1 infected ART-naïve adult study participants in four hospitals Addis Ababa. CD4+ T-cell count, HIV RNA load, hemoglobin and fasting serum total cholesterol were determined. Socio-demographic characteristics, WHO clinical stages, and height and weight were collected from patients' chart and triangulated by structured questionnaire. Pearson chi-square test, Spearman rank correlation and univariate and multivariate linear/logistic regression analyses were carried out to determine associations. RESULTS: Mean HIV RNA load was found to be lower in women than in men (p < 0.05). CD4+ T cell count and serum total cholesterol were found to be significantly correlated with HIV RNA load (p < 0.01). Women were at lower risk of having higher HIV RNA load in comparison to men. In addition, having lower concentrations of serum total cholesterol was found to be independent predictor of higher HIV RNA load in comparison to those with higher concentrations of cholesterol in serum (p < 0.05). The multivariate binomial logistic regression also showed that the immune status was better in women than men, and in the presence of higher serum total cholesterol (p < 0.05). CONCLUSION: Gender and serum total cholesterol were found to be associated and independent predictors of HIV RNA load, and CD4+ cell count and/or WHO clinical stages. There is a significant lower HIV RNA load and better CD4+ T cell count in women and those study participants with higher serum total cholesterol.

Incidence of low-level viremia and its impact on virologic failure among people living with HIV-1 who switched to elvitegravir-based antiretroviral therapy.

OBJECTIVES: We aimed to investigate the incidence of low-level viremia (LLV) and its impact on virologic failure (VF) in people living with HIV (PLWH) on stable antiretroviral therapy (ART) who switched to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/c/FTC/TAF). METHODS: PLWH aged 18 years or older who had received ART with plasma HIV RNA load (PVL) <50 copies/mL for 6 months or longer and switched to EVG/c/FTC/TAF between March and October 2018 were retrospectively included. The incidence of LLV (defined as PVL of 50-999 copies/mL) and VF (PVL ≥1000 copies/mL) was calculated and represented by Kaplan-Meier plots. The generalised estimating equation model was constructed to identify factors associated with LLV and VF. Resistance-associated mutations were determined using population sequencing. RESULTS: A total of 1078 PLWH were included. The incidence rates of LLV and VF after the switch to EVG/c/FTC/TAF were 3.5 and 0.8 events per 100 person-years of follow-up, respectively, whereas the respective cumulative incidence of LLV and VF reached 11.7% and 2.9% within 3 years of follow-up. LLV was associated with any LLV episode before or after the switch and prior exposure to integrase strand transfer inhibitor-based ART. VF was associated with any LLV before or after the switch and prior exposure to raltegravir, but not the level or frequency of LLV. CONCLUSION: The risks of LLV and VF were low in PLWH who had achieved virologic suppression and switched to EVG/c/FTC/TAF, and the presence of LLV and prior exposure to raltegravir increased the risk of VF.

A Subset of Extreme Human Immunodeficiency Virus (HIV) Controllers Is Characterized by a Small HIV Blood Reservoir and a Weak T-Cell Activation Level.

BACKGROUND: Human immunodeficiency virus controllers (HICs) form a heterogeneous group of patients with regard to formal definitions, immunologic characteristics, and changes over time in viral load. PATIENTS AND METHODS: The HICs with undetectable viral load ([uHICs] ie, for whom a viral load had never been detected with routine assays; n = 52) were compared with 178 HICs with blips during the follow up (bHICs). Clinical characteristics, ultrasensitive HIV-ribonucleic acid (RNA) and HIV-deoxyribonucleic acid (DNA) loads, HIV1-Western blot profiles, and immune parameters were analyzed. RESULTS: Relative to bHICs, uHICs had significantly lower ultrasensitive plasma HIV-RNA loads (P < .0001) and HIV-DNA levels in peripheral blood mononuclear cells (P = .0004), higher CD4+ T-cell count (P = .04) at enrollment, and lower T-cell activation levels. Between diagnosis and inclusion in the cohort, the CD4+ T-cell count had not changed in uHICs but had significantly decreased in bHICs. Twenty-one percent of the uHICs lacked specific anti-HIV immunoglobulin G antibodies, and these individuals also had very low levels of HIV-DNA. Half of the uHICs had a protective human leukocyte antigen (HLA) allele (-B57/58/B27), a weak CD8+ T-cell response, and very small HIV-DNA reservoir. CONCLUSIONS: We suggest that an interesting HIC phenotype combines protective HLA alleles, low level of HIV blood reservoirs, and reduced immune activation. Prospective studies aimed at evaluating the benefit of combined antiretroviral therapy in HICs might take into account the identification of uHICs and bHICs.

Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy.

HIV-infected patients remain at higher risk for pneumococcal disease than the general population despite immune reconstitution and suppression of HIV replication with combination antiretroviral therapy. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) composed of T-cell-independent antigens has been recommended to reduce the risk of pneumococcal disease in HIV-infected adults. However, given the heterogeneity of study design, execution and subjects enrolled, studies examining serological responses to PPV23 yielded conflicting results and observational studies of clinical effectiveness only provided moderate evidence to support the routine use of PPV23 in HIV-infected adults. Pneumococcal conjugate vaccine (PCV), with conjugation of the capsular polysaccharide to a protein carrier, is more immunogenic than PPV23 and has been demonstrated to protect against pneumococcal disease in HIV-infected children and recurrent invasive pneumococcal disease in HIV-infected adolescents and adults. Guidelines have recently been revised to recommend that HIV-infected patients aged 19 y or older receive one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with PPV23. In this paper, we review the studies using different vaccination strategies to improve immunogenicity among HIV-infected adult patients.