Outcomes of Methadone Maintenance Therapy Combined with Rilpivirine/Efavirenz in Treatment-Naive HIV-Infected Patients.

BACKGROUND: Injecting drugs is associated with a high risk of HIV infection, alongside the risk of a drug overdose and mental health problems. OBJECTIVE: To evaluate the effect of methadone maintenance treatment (MMT) combined with rilpivirine (RPV)-based regimens on drug use of HIV individuals. METHODS: This study was a prospective, open-label, controlled, drug-drug interaction trial at a single center for 24 weeks. Participants on stable MMT were randomly divided into two groups administered RPV/TDF/3TC (RPV group) and EFV/TDF/3TC (EFV group), respectively. Adjustment doses of methadone were monitored for 12 weeks. HIV-1 RNA was used to evaluate the effects of antiretroviral therapy at week 24. Acute opioid withdrawal-, drug craving questionnaire- and MOSHIV scales were used to assess study outcomes. RESULTS: 22 and 18 cases of HIV-infected drug users were recruited in the RPV and EFV groups, respectively. Thirty-one cases had completed monitoring and clinical evaluation at week 24. In the RPV and EFV groups, 32% and 56% of the participants had methadone dose adjustment, respectively, indicating a significantly lower rate in the RPV group. The rates of individuals with HIV RNA levels from 50-500 copies/ml were 94% (RPV group) and 90% (EFV group). The drug craving questionnaire scale scores decreased in both groups. After one week of treatments, acute opioid withdrawal scale scores increased in both groups, with no significant difference between them. CONCLUSION: Concomitant administration of RPV does not significantly affect methadone and could decrease withdrawal symptoms. An RPV-based regimen may be used as first-line treatment in IDUs with HIV infection.

Thrombotic antiphospholipid syndrome in a child with human immunodeficiency virus: a rare case report.

BACKGROUND: Antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disorder induced by antiphospholipid antibodies, which occurs exceedingly rarely in pediatric population and even more rarely reported in HIV positive children. A case of 11 years old boy had a sudden onset of swelling in his left lower leg along with pain which were worsening gradually. Initially, topical ointment was applied for 1 month which were ineffective in reducing pain and swelling. Instead, the symptoms were aggravated and suddenly spread to the proximal thigh, accompanied by dyskinesia of left lower leg. Both color doppler ultrasonography and vascular CT scan of left lower leg revealed deep venous thrombosis. His serum anti-phospholipid antibodies (aPLs) were tested positive. He was a known case of HIV virological failure with substantial HIV viral load (VL) despite receiving regular antiretroviral therapy (ART). His symptoms improved after giving aggressive antithrombotic and high dose corticosteroid treatments. CONCLUSION: When pediatric patients develop thrombotic disease, APS also needs to be ruled out. The autoantibodies levels should be routinely tested to look for recurrent thrombosis in children with HIV/AIDS.

Effect of rilpivirine on the pharmacokinetics of methadone in HIV-Infected Chinese patients.

Background: The combination of rilpivirine with methadone may result in complex interactions secondary to the induction of oxidative metabolism by rilpivirine. Research design and methods: TMC278IFD4007 was a single-center, prospective, open-label, multiple-dose study with 12 HIV-infected Chinese participants. The objective was to evaluate the potential effect of rilpivirine on the pharmacokinetics of methadone. The participants received a daily dose of 25 mg rilpivirine for 11 days with individualized methadone ranging from 25 to 100 mg. Pharmacokinetic studies of methadone were conducted on day 1 and 11. Opiate withdrawal symptoms were evaluated. Results: A large inter-subject variability was noted in methadone pharmacokinetics. Rilpivirine increased methadone minimum and maximum plasma concentrations (Cmin; Cmax) and area under the plasma concentration-time curve versus methadone alone (least-square mean ratio; 90% confidence interval) by 5% (1.05; 0.46, 2.39), 5% (1.05; 0.73, 1.52), and 6% (0.75; 0.74, 1.50) as measured in S-methadone, and 5% (1.05; 0.50, 2.22), 5% (1.05; 0.74, 1.50), and 5% (1.05; 0.76, 1.46) as measured in R-methadone, respectively. No opioid withdrawal symptoms or methadone dose adjustments were reported. Co-administration was well tolerated without serious adverse effects or discontinuations. Conclusion: Concomitant administration of rilpivirine was unlikely to have significant effects on the pharmacokinetics of methadone.

Tolerable and curable treatment in HIV/HCV co-infected patients using anti-HCV direct antiviral agents: a real-world observation in China.

OBJECTIVE: No brand direct-acting antiviral agents (DAAs) are available for treatment of HIV-1/HCV co-infected patients in China. This study aimed to observe the therapeutic efficacy and safety of generic DAAs for affected Chinese patients. DESIGN: Real-world setting to elucidate whether DAAs were tolerated and effective in HIV-1/HCV co-infected patients. METHODS: 176 HIV-1/HCV co-infected patients received anti-HCV DAA treatment together with ART regimens for HIV infection. Among the 176 patients, 99 patients were treated with SOF + DCV ± RBV, 60 patients were treated with SOF + LDV ± RBV, and 17 patients received SOF + RBV ± Peg-IFN regimens, for 12 or 24 weeks, respectively. The primary endpoint was undetectable HCV RNA 12 weeks after therapy was completed (SVR12). Data pertaining to safety and adverse events were analyzed. RESULTS: 151/176 HIV-1/HCV co-infected patients finished the treatment and 12-week follow-up. SVR12 for the patients treated with regimens of SOF + DCV, SOF + DCV+RBV, SOF + Peg-IFN+RBV, SOF + RBV, SOF + LDV, and SOF + LDV+RBV for 12 or 24 weeks was 100% (75/75), 100% (11/11), 100% (14/14), 100% (2/2), 95.2% (40/42), and 100% (7/7), respectively. HIV-1/HCV co-infected patients with liver cirrhosis achieved well SRV12. Notably, there was no significant difference in adverse effects among patients with different baseline CD4+ T-cell count in those who received DAA regimens with or without Peg-IFN and RBV. CONCLUSION: We showed generic SOF + DCV and SOF + LDV regimens were well tolerated and with high efficiency. Patient's baseline CD4+ T-cell count did not exhibit significant difference in adverse effects.

Quantitative analysis of erythromycylamine in human plasma by liquid chromatography-tandem mass spectrometry and its application in a bioequivalence study of dirithromycin enteric-coated tablets with a special focus on the fragmentation pattern and carryover effect.

A liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of erythromycylamine, which is the predominant active metabolite of dirithromycin in human plasma. After solid-phase extraction, the analyte and internal standard (IS) were separated by using an isocratic mobile phase consisting of 20 mM ammonium acetate (pH 3.9, adjusted with formic acid)-acetonitrile (75:25, v/v) on a Phenyl-Hexyl column (150 × 2.1 mm, 3 µm) and then analyzed in positive ion mode under electrospray ionization. Azithromycin was selected as the IS because it has the most similar mass spectrometric and chromatographic behaviors to the analyte. The respective multiple reaction monitoring (MRM) transitions, m/z 368.5>83.2 for erythromycylamine and m/z 375.4>115.2 for IS were chosen to achieve high sensitivity and selectivity in determination. A more acidic mobile phase (pH 3.9) than those of previous reports and a special needle wash (ethylene glycol-acetonitrile-water, 50:30:20, v/v/v, adjusted to pH 3.9 using formic acid) were used to eliminate the carryover effects of the two macrolides. The method exhibited a linear dynamic range of 0.5-440.0 ng/mL for erythromycylamine in human plasma (r=0.9999). The lower limit of quantification (LLOQ) and limit of detection (LOD) were 0.5 and 0.05 ng/mL, respectively. The mean extraction recoveries were higher than 94.0% for the analyte and IS. The intra- and inter-day precisions ranged from 1.4 to 5.4% and from 1.6 to 4.0%, respectively. The accuracy varied between 91.2 and 101.2%. The established method was successfully applied to analyze the human plasma samples from 24 healthy subjects in a bioequivalence study of two dirithromycin enteric-coated formulations.

[Specific causes of death among 381 AIDS patients who died in hospitals].

OBJECTIVE: In this study, researchers investigated the demographic and clinical characteristics of AIDS patients who died in hospitals, analyzed the specific causes of death, and looked for the correlation between specific cause of death and their clinical characteristics. METHODS: Data of clinical characteristics of patients and their specific causes AIDS of death who died in the seven hospitals from 2009 to 2010 were collected retrospectively. All the specific causes of death were classified according to the Cause of Death (CoDe) project protocol. Univariate analysis and multivariate logistic regression analysis were used to find the association between some categorical variables and the risk for AIDS patients died from AIDS related illnesses. RESULTS: Clinical characteristics and the cause of death of the 381 deceased in seven hospitals in this study were collected. 82.4% were male, with priority as 30-45 years old. 123 (32.3%) death patients had received ART before death. In all death cases, the cause of death of 252 patients (66.1%) were due to AIDS related diseases, with opportunistic infections the most (92.4%). Tubercle bacillus, infection of Penicillium marneffei and Pneumocystis jiroveci were the three leading causes of opportunistic infection deaths. Of 129 patients who died of non-AIDS related disease, non-AIDS infection (29.5%), hepatitis (22.5%), and non-AIDS malignancy(10.1%)were the first three causes of death. The cause of death in patients who had injecting drug use behavior within one year, had not received ART or not long enough, with opportunistic infections, without hepatitis, with the last low CD4 cell counts before death etc. were tend to due to AIDS related disease. CONCLUSION: Opportunistic infections, non-AIDS related infections and hepatitis were the three leading causes of death in this study. The duration of time on ART had impact on the patient's cause of death. The HIV infected patients who had received ART before death had more risk to die of non-AIDS related disease, compared to patients who had not. The longer time they had accessed to ART, the less likely they would die on non-AIDS related illnesses.

[Expression of B7-H1 on peripheral myeloid dendritic cells in patients with HIV infection and its correlation with diseases progression].

OBJECTIVE: To investigate the features of B7-H1 expression on peripheral myeloid dendritic cells (mDCs) in patients with HIV infection and evaluate the correlations between B7-H1 expression and disease progression. METHODS: Peripheral blood samples from 82 treatment-naïve patients with HIV infection, 28 viral complete responders (CRs) under antiretroviral therapy (ART) and 14 healthy controls (HCs) were collected. Flow cytometry was applied to investigate the expression of B7-H1 on mDCs and CD4 cell counts. Plasma HIV-1 viral load was detected by bDNA. RESULTS: The frequency of B7-H1 expression on mDCs were 14.15% +/- 2.63%, 3.31% +/- 0.51% and 0.52% +/- 0.10% in AIDS patients, asymptomatic HIV infected individuals and HCs respectively. As compared with HCs, B7-H1 was significantly up-regulated on mDCs in HIV/AIDS patients. The order was as follows: AIDS patients > asymptomatic HIV infected individuals > HCs (all P < 0.05). Interestingly, the expression of B7-H1 on mDCs in long-term nonprogressors (LTNPs) was 3.12% +/- 1.14%. And it was lower than that in typical progressors (TPs) [8.12% +/- 1.37% (P = 0.001)]. Moreover, the expression of B7-H1 was negatively correlated with CD4 cell counts and positively correlated with plasma viral load in these patients (r = -0.631, P < 0.01 and r = 0.482, P < 0.01 respectively). The expression of B7-H1 on mDCs was significantly lower in ART complete responders than that in AIDS patients (6.59% +/- 1.43% vs 14.15% +/- 2.63%) (P < 0.01). Expression of B7-H1 on mDCs decreased markedly in patients whose CD4 cell counts greatly elevated after a successful antiretroviral treatment. CONCLUSION: The expression of B7-H1 on mDCs is significantly up-regulated in HIV/AIDS patients. With a close correlation with disease status, it acts as a marker of disease progression.