Challenges in Providing Treatment and Care for Viral Hepatitis among Individuals Co-Infected with HIV in Resource-Limited Settings

Hepatitis B and C infections are prevalent among HIV-infected individuals with different epidemiologic profiles, modes of transmission, natural histories, and treatments. Southeast Asian countries are classified as “highly prevalent zones,” with a rate of hepatitis B and C coinfection in people living with HIV/AIDS of approximately 3.2–11%. Majority of hepatitis B coinfection is of genotype C. Most of the patients infected with hepatitis C in Thailand have genotype 3 which is significantly related to intravenous drug use whereas, in Vietnam, it is genotype 6. The options for antiretroviral drugs are limited and rely on global funds and research facilities. Only HBV treatment is available for free through the national health scheme. Screening tests for HBV and HCV prior to commencing antiretroviral treatment are low. Insufficient concern on hepatitis-virus-related liver malignancy and long-term hepatic morbidities is noted. Cost-effective HCV treatment can be incorporated into the national health program for those who need it by utilizing data obtained from clinical research studies. For example, patients infected with HCV genotype 2/3 with a certain IL-28B polymorphism can be treated with a shorter course of interferon and ribavirin which can also help reduce costs

Hemoglobin Levels Influence Pharmacokinetics of Tacrolimus in Kidney Transplant Patients

AbstractObjective: To determine the relationship between hemoglobin levels andpharmacokinetics of tacrolimus in Thai kidney transplant patients.Methods: The clinical data of 71 kidney transplant recipients at KingChulalongkorn Memorial Hospital, Bangkok were retrospectively collectedduring 1 to 6 months after initiation of tacrolimus treatment. The ratio ofdose to trough whole-blood concentrations of tacrolimus (D/Ctrough) wascalculated. Linear regression was used to determine the relationshipbetween hemoglobin levels and D/Ctrough.Results: Hemoglobin levels wereinversely associated with D/Ctrough (r = -0.41, P < 0.01). The relationshipcould be described as an equation (D/Ctrough (L/kg) = 26.38 - 1.44Hemoglobin (g/dl)). Furthermore, D/Ctrough was significantly higher in thepatients with low hemoglobin levels (<12 g/dL) than those with normalhemoglobin levels (11.10 8.73 vs 7.31 4.05 L/kg, respectively).Conclusion: The ratio of dose to trough concentrations of tacrolimussignificantly correlates with hemoglobin levels. We should considerhemoglobin levels of kidney transplant patients whenever modifying theirtacrolimus dosage.Keywords: hemoglobin, kidney transplant, pharmacokinetics, tacrolimusบทคัดย่อวัตถุประสงค์: เพื่อศึกษาหาความสัมพันธ์ระหว่างระดับ hemoglobin และเภสัชจลนศาสตร์ของยา tacrolimus ในผู้ป่วยไทยที่ได้รับการปลูกถ่ายไต วิธีการศึกษา: ทำการศึกษาแบบย้อนหลังในผู้ป่วยปลูกถ่ายไต จำนวน 71 คน ที่มาติดตามการรักษา ณ โรงพยาบาลจุฬาลงกรณ์ กรุงเทพ โดยเก็บข้อมูลระดับความเข้มข้นยาจากเวชระเบียน ในระยะ 1 ถึง 6 เดือนหลังได้รับยา tacrolimus คำนวณหาค่าสัดส่วนขนาดยาต่อความเข้มข้นของยา tacrolimus ในเลือดที่เวลาก่อนให้ยามื้อถัดไป (D/Ctrough) และหาความสัมพันธ์ระหว่างระดับ hemoglobin และ D/Ctrough โดยการวิเคราะห์ความถดถอยเชิงเส้น ผลการศึกษา: จากการศึกษาพบว่า ระดับ hemoglobin มีความสัมพันธ์เชิงลบกับค่า D/Ctrough (r = -0.41, P < 0.01) และได้สมการทำนายค่าสัดส่วนขนาดยาต่อความเข้มข้นยาคือ D/Ctrough (L/kg) = 26.38 - 1.44 Hemoglobin (g/dl) นอกจากนั้นค่า D/Ctrough ใน กลุ่มผู้ป่วยที่มีระดับ hemoglobin ต่ำกว่า 12 กรัม/ดล. มีค่าสูงกว่ากลุ่มผู้ป่วยที่มีระดับ hemoglobin ปกติอย่างมีนัยสำคัญทางสถิติ (11.10 8.73 และ 7.31 4.05 L/kg ตามลำดับ). สรุป: ค่าสัดส่วนขนาดยาต่อความเข้มข้นของยา tacrolimus ที่เวลาก่อนให้ยามีความสัมพันธ์กับระดับ hemoglobin การเปลี่ยนแปลงของระดับ hemoglobin อาจช่วยในการปรับขนาดใช้ยา tacrolimus ให้มีความปลอดภัยและประสิทธิผลดีในผู้ป่วยปลูกถ่ายไตคำสำคัญ: hemoglobin, kidney transplant, pharmacokinetics, tacrolimus

A machine learning strategy for predicting localization of post-translational modification sites in protein-protein interacting regions

Definitions of true positives (TP), false positives (FP), true negatives (TN), and false negatives (FN) in this study. (DOCX 18 kb

Nevirapine versus Efavirenz for patients co-infected with HIV and Tuberculosis: A Randomised Non-Inferiority Trial

BACKGROUND: In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare efficacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in co-infected patients. METHODS: We did a multicentre, open-label, randomised, non-inferiority trial at three health centres in Maputo, Mozambique. We enrolled adults (≥18 years) with tuberculosis and previously untreated HIV infection (CD4 cell counts <250 cells per μL) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal. 4-6 weeks after the start of tuberculosis treatment, we randomly allocated patients (1:1) with central randomisation, block sizes of two to six, and stratified by site and CD4 cell count to nevirapine (200 mg twice daily) or efavirenz (600 mg once daily), plus lamivudine and stavudine. The primary endpoint was virological suppression at 48 weeks (HIV-1 RNA <50 copies per mL) in all patients who received at least one dose of study drug (intention-to-treat population); death and loss to follow-up were recorded as treatment failure. The non-inferiority margin for the difference of efficacy was 10%. We assessed efficacy in intention-to-treat and per-protocol populations and safety in all patients who received study drug. This study is registered with ClinicalTrials.gov, number NCT00495326. FINDINGS: Between October, 2007, and March, 2010, we enrolled 285 patients into each group. 242 (85%) patients in the nevirapine group and 233 (82%) patients in the efavirenz group completed follow-up. In the intention-to-treat population, 184 patients (64·6%, 95% CI 58·7-70·1) allocated nevirapine achieved virological suppression at week 48, as did 199 patients (69·8%, 64·1-75·1) allocated efavirenz (one-sided 95% CI of the difference of efficacy 11·7%). In the per-protocol population, 170 (70·0%, 63·8-75·7) of 243 patients allocated nevirapine achieved virological suppression at week 48, as did 194 (78·9%, 73·2-83·8) of 246 patients allocated efavirenz (one-sided 95% CI 15·4%). The median CD4 cell count at randomisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine. 20 patients allocated nevirapine (7%) had grade 3-4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz (6%). Three patients had severe rash after receipt of nevirapine (1%) but no patients did after receipt of efavirenz. 18 patients in the nevirapine group died, as did 17 patients in the efavirenz group. INTERPRETATION: Although non-inferiority of the nevirapine-regimen was not shown, nevirapine at full dose could be a safe, acceptable alternative for patients unable to tolerate efavirenz. FUNDING: French Research Agency for HIV/AIDS and hepatitis (ANRS)

Assessment of HBV flare in a randomized clinical trial in HIV/HBV coinfected subjects initiating HBV-active antiretroviral therapy in Thailand

BACKGROUND: Hepatic Flare (HF) after initiation of highly active antiretroviral therapy (HAART) in HIV-HBV coinfected individuals is well recognized but prospective data on predictors and subsequent outcome are limited. METHODS: The Tenofovir in HIV-HBV coinfection study was a randomized clinical trial of HBV-active HAART including lamivudine and/or tenofovir in antiretroviral naïve HIV-HBV individuals in Thailand. RESULTS: Early HF (EHF) was defined as ALT > 5 × ULN during the first 12 weeks. EHF was observed in 8 (22%) of individuals at a median of 56 days. 6/8 EHF cases were asymptomatic and resolved with HAART continuation, however one subject with underlying cirrhosis died following rapid hepatic decompensation. EHF was significantly associated with higher baseline ALT (79 IU/L vs 36 IU/L non-EHF, p = 0.008) and HBV DNA (9.9 log10 c/ml vs 8.4 log10 c/ml non EHF, p = 0.009), and subsequent serological change. HBeAg loss occurred in 75% of EHF cases versus 22% in non-EHF (p = 0.04), and HBsAg loss in 25% of EHF cases versus 4% of non-EHF (p = 0.053). CONCLUSION: EHF after HBV active HAART initiation was frequently observed in this population. Timing of EHF, association with elevated ALT and HBV DNA and high rate of seroconversion are all consistent with immune restoration as the likely underlying process. CLINICAL TRIAL NUMBER: NCT00192595

Adherence and Risk Behaviour in Patients with HIV Infection Receiving Antiretroviral Therapy in Bangkok

It could be postulated that due to lifestyle factors, patients with poor antiretroviral therapy (ART) adherence may also have risky sexual behaviour potentially leading to HIV transmission. There are limited data regarding unprotected sex risk and ART adherence in resource limited settings and our study set out to investigate these in an HIV clinic in Bangkok. Patients completed an anonymous questionnaire regarding their relationship details, ART adherence, sexual behaviour, alcohol and drug use and HIV transmission beliefs. Laboratory findings and medical history were also collected. Unprotected sex risk (USR) was defined as inconsistent condom use with a partner of negative or unknown HIV status. Five hundred and twelve patients completed the questionnaire. Fifty seven per cent of patients reported having taken ARV >95% of the time in the last month and 58% had been sexually active in the previous 30 days. Only 27 patients (5%) were classified as having USR in our cohort. Multivariate analysis showed USR was associated with female gender (OR 2.9, 95% CI 1.2-7.0, p0.02) but not with adherence, age, type or number of partners, recreational drug or alcohol use nor beliefs about HIV transmission whilst taking ART. Levels of USR in this resource limited setting were reassuringly low and not associated with poor ART adherence; as all USR patients had undetectable viral loads onward HIV transmission risk is likely to be low but not negligible. Nonetheless condom negotiation techniques, particularly in women, may be useful in this group