Hepatitis: Sungkanuparph S

Sungkanuparph S, Anekthananon T, Hiransuthikul N, Bowonwatanuwong C, Supparatpinyo K, Mootsikapun P, Chetchotisakd P, Kiertiburanakul S, Tansuphaswadikul S, Buppanharun W, Manosuthi W, Techasathit W, Ratanasuwan W, Tantisiriwat W, Suwanagool S, Leechawengwongs M, Ruxrungtham K, Anonymous00067. · Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand. · J Med Assoc Thai. · Pubmed #19133532 No free full text.

Abstract: BACKGROUND: More than 100,000 patients have been treated, since the implementation of the National Universal Coverage for antiretroviral therapy (ART) in Thailand Although there are several comprehensive guidelines available internationally, there is a need to have guidelines that can be implemented in Thailand. MATERIAL AND METHOD: The guidelines were developed by a panel of 17 members who are the experts on HIV research and/or HIV patient care and appointed without incentive by the Thai AIDS Society (TAS). The recommendations were based on evidences from the published studies and availability of antiretroviral agents. Published studies that are relevant and applicable to Thailand in particular have been taken into consideration. RESULTS: The recommendations include: when to start ART; what to start; how to monitor the therapy; adverse effects and its management; diagnosis of treatment failure; and antiretroviral treatment options in patients with treatment failure. ART in special circumstances, i.e., patients with co-infection of tuberculosis or hepatitis B virus, is also included Appropriate level of CD4+ T-cell count to start ART among Thai patients has been considered carefully. The authors recommend to start ART at CD4+ T-cell count < 200 cells/mm3. CONCLUSION: ART should be initiated in adults and adolescents HIV-1 infected patients with a history of HIV-related illness or AIDS or with a CD4+ T-cell count <200 cells/mm3. For treatment-naive patients, the preferred initial therapy is a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. CD4' T-cell count and viral load should be monitored for at least twice and once a year, respectively. Proper management of antiretroviral-related toxicity and enhancement of adherence are crucial for the long-term success of ART.

Egger S, Petoumenos K, Kamarulzaman A, Hoy J, Sungkanuparph S, Chuah J, Falster K, Zhou J, Law MG, Anonymous00073. · Cancer Council New South Wales, Woolloomooloo, Sydney, New South Wales, Australia. · J Acquir Immune Defic Syndr. · Pubmed #19408354 No free full text.

Abstract: BACKGROUND: Random effects models were used to explore how the shape of CD4 cell count responses after commencing combination antiretroviral therapy (cART) develop over time and, in particular, the role of baseline and follow-up covariates. METHODS: Patients in Asia Pacific HIV Observational Database who first commenced cART after January 1, 1997, and who had a baseline CD4 cell count and viral load measure and at least 1 follow-up measure between 6 and 24 months, were included. CD4 cell counts were determined at every 6-month period after the commencement of cART for up to 6 years. RESULTS: A total of 1638 patients fulfilled the inclusion criteria with a median follow-up time of 58 months. Lower post-cART mean CD4 cell counts were found to be associated with increasing age (P < 0.001), pre-cART hepatitis C coinfection (P = 0.038), prior AIDS (P = 0.019), baseline viral load < or equal to 100,000 copies per milliliter (P < 0.001), and the Asia Pacific region compared with Australia (P = 0.005). A highly significant 3-way interaction between the effects of time, baseline CD4 cell count, and post-cART viral burden (P < 0.0001) was demonstrated. Higher long-term mean CD4 cell counts were associated with lower baseline CD4 cell count and consistently undetectable viral loads. Among patients with consistently detectable viral load, CD4 cell counts seemed to converge for all baseline CD4 levels. CONCLUSIONS: Our analysis suggest that the long-term shape of post-cART CD4 cell count changes depends only on a 3-way interaction between baseline CD4 cell count, viral load response, and time.

Sungkanuparph S, Wongprasit P, Manosuthi W, Atamasirikul K. · Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. · Southeast Asian J Trop Med Public Health. · Pubmed #19058581 No free full text.

Abstract: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important risk factors for mortality among HIV-infected patients. We assessed compliance with screening for HBV and HCV infection prior to initiation of ART in a resource-limited setting. Six hundred thirty-eight patients with a mean age of 38.4 years (53% males) were studied. Prior to initiation of antiretroviral therapy (ART) 371 patients (58%) were screened for HBV and 273 (43%) were screened for HCV infection. Of those screened, 9.7% had HBV infection and 8.8% had HCV infection. Given the relatively high prevalence of HBV and HCV infection among HIV-infected patients, screening for HBV and HCV infections prior to ART initiation should not be omitted in the resource-limited setting.

Manosuthi W, Sungkanuparph S, Tansuphaswadikul S, Chottanapund S, Mankatitham W, Chimsuntorn S, Sittibusaya C, Moolasart V, Chaovavanich A. · Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand. · J Med Assoc Thai. · Pubmed #18389979 No free full text.

Abstract: OBJECTIVES: To determine incidence and risk factors of nevirapine (NVP)-associated severe hepatitis that led to NVP discontinuation among HIV-infected patients with CD4 < 250 cells/microL. MATERIAL AND METHOD: A retrospective cohort study was conducted among antiretroviral-naïve HIV-infected patients who had baseline CD4 < 250 cells/microL and were initiated NVP-based antiretroviral therapy (ART) between January 2003 and October 2005. All patients were categorized to group A: occurred clinical hepatitis and group B: did not occur clinical hepatitis. All were followed until 6 months after ART. RESULTS: There were 910 patients with a mean age of 35.4 years, 57% were males and median (IQR) CD4 cell count was 27 (9-80) cells/microL; contributing 5,006 person-months of observations. Ten (1.1%) patients were in group A and 900 (98.9%) patients were in group B. Incidence of clinical hepatitis was 2 per 1,000 person-months. Probabilities of clinical hepatitis at 0.5, 1, 2, 3 and 6 months after ART were 0.2%, 0.5%, 0.7%, 0.8% and 1.1%, respectively. By Cox regression analysis, baseline AST > or = 1.5 times of upper limit was associated with higher incidence of clinical hepatitis (p = 0.019, HR = 5.83, 95% CI = 1.33-25.51). CONCLUSION: Incidence of NVP-associated severe hepatitis that lead to NVP discontinuation among HIV-infected patients with baseline CD4 < 250 cells/microL is low. The higher baseline AST is also associated with a higher risk of severe hepatitis.

Ungulkraiwit P, Jongjirawisan Y, Atamasirikul K, Sungkanuparph S. · Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. · Southeast Asian J Trop Med Public Health. · Pubmed #17883006 No free full text.

Abstract: This study aimed to determine the predicting factors for successful hepatitis B vaccination among HIV-1 infected patients. A prospective study was conducted among HIV-1 infected patients who had negative HBV serologies. Anti-HBs antibody was evaluated one month after completing a 3-injection course of hepatitis B vaccine. Patients who had an anti-HBs antibody level >10 mlU/ml were defined as responders. There were 65 patients with a mean age of 39+/-8.5 years, 68% were females. Fifty-seven (88%) patients had received antiretroviral therapy for a mean (SD) duration of 26.1 (22.3) months and 75% of these had an HIV-1 RNA count <50 copies/ml. The mean (SD) CD4 cell count and percentage at the time of vaccination were 345 (194) cells/mm3 and 16 (7) %, respectively. Thirty patients (46%) were responders. Compared to non-responders, responders had a higher mean CD4 cell count (p = 0.047) and a trend toward a younger age (p = 0.052). On multivariate analysis, younger age (p = 0.049) and higher CD4 cell count (p = 0.048) were predictors for successful response to hepatitis B vaccination. Determination of antibody levels after vaccination in HIV-infected patients is warranted.

Manosuthi W, Athichathanabadi C, Uttayamakul S, Phoorisri T, Sungkanuparph S. · Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand. · BMC Infect Dis. · Pubmed #17352798 links to  free full text

Abstract: BACKGROUND: The clinical data of plasma NVP level, safety and efficacy of antiretroviral therapy (ART) for the concurrent use of nevirapine (NVP)-based ART and fluconazole (FLU) is scanty. METHODS: A retrospective study was conducted in patients who were initiated NVP-based ART between October 2004 and November 2005. The objectives were to compare NVP levels, adverse events, and 36-week efficacy of NVP-based ART between patients who did not receive FLU (group A) and those who received FLU 200 mg/day or 400 mg/day (group B). RESULTS: There were 122 patients with mean +/- SD age of 36 +/- 9 years; 81 in group A and 41 in group B. Median (IQR) baseline CD4 cell count was 29 (8-79) cell/mm3 in group A and 19 (8-33) cell/mm3 in group B (P = 0.102). Baseline characteristics between the two groups were similar. Mean +/- SD NVP levels were 6.5 +/- 3.0 mg/L in group A and 11.4 +/- 6.1 mg/L in group B(P < 0.001). One (2.4%) patient in group B developed clinical hepatitis (P = 0.336). Six (7.4%) patients in group A developed NVP-related skin rashes (P = 0.096). There were no differences in term of 36-week antiviral efficacy between the two groups (P > 0.05). CONCLUSION: Co-administration of NVP and daily dosage of FLU (200 mg/day and 400 mg/day) results in markedly increased trough plasma NVP level when compared to the administration of NVP alone. The concurrent use of NVP and FLU in very advanced HIV-infected patients is well-tolerated. The immunological and virological responses are favorable.

Overton ET, Nurutdinova D, Sungkanuparph S, Seyfried W, Groger RK, Powderly WG. · Washington University School of Medicine, St Louis, MO, USA. · J Viral Hepat. · Pubmed #17305885 No free full text.

Abstract: Hepatitis A virus (HAV) infection remains a health risk for human immunodeficiency virus (HIV)-infected persons. While the inactivated HAV vaccine affords protection to immunocompetent persons >95% of the time, rates of developing protective antibody (anti-HAV) in HIV+ persons are considerably lower. Although low CD4+ T-cell counts have previously been reported to be correlated with this poor response, the effect of HIV viraemia on HAV vaccine response has not previously been reported. The medical records of HIV-infected patients who had received at least one dose of HAV vaccine (Havrix, 1440 EIU) were reviewed for factors associated with the development of a protective anti-HAV response. Serological data with regard to anti-HAV status after vaccination were available in 238 patients with 133 individuals (49.6%) developing immunity after vaccination. In a logistic regression model, the only factors associated with a protective antibody response were an HIV plasma RNA level <1000 copies/mL at the time of vaccination (P = 0.011) and male gender (P = 0.016). Neither nadir CD4+ T cell count nor CD4+ T-cell count at time of vaccination were predictive of the development of anti-HAV. Suppression of HIV replication at time of vaccination is associated with a protective antibody response to HAV vaccination in HIV-infected adults. The low rate of response warrants further research in alternative strategies for HAV vaccination among HIV-infected persons.

Jongjirawisan Y, Ungulkraiwit P, Sungkanuparph S. · Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. · J Med Assoc Thai. · Pubmed #17214053 No free full text.

Abstract: BACKGROUND: Isolated antibody to hepatitis B core antigen (anti-HBc) is frequently found in HIV-infected patients. The present study aimed to determine the prevalence and risk factors of isolated anti-HBc and the anamnestic response to hepatitis B vaccination in this population. MATERIAL AND METHOD: HIV-infected patients who visited Ramathibodi Hospital in May 2006 were included to test hepatitis B serology. Subjects with isolated anti-HBc were given hepatitis B vaccine and tested for anti-HBs. RESULTS: Of 140 patients, 28 (20%) had isolated anti-HBc. From multivariate analysis, IVDU (OR 30.8, p < 0.001) and anti-HCV seropositive (OR 6.7, p = 0.002) were independent risk factors for isolated anti-HBc. Two from 28 (7%) patients who received vaccine had a response to vaccination. CONCLUSION: Prevalence of isolated anti-HBc among Thai HIV-infected patients was 20%. Risk factors of isolated anti-HBc were IVDU and anti-HCV seropositive. Anamnestic response to hepatitis B vaccination was low. Further study with strategies to improve the response of vaccination is needed.

Overton ET, Sungkanuparph S, Powderly WG, Seyfried W, Groger RK, Aberg JA. · Washington University School of Medicine, St. Louis, MO 63110, USA. · Clin Infect Dis. · Pubmed #16142673 No free full text.

Abstract: Human immunodeficiency virus (HIV)-infected patients respond poorly to hepatitis B vaccination. Records of 194 HIV-infected patients were reviewed for factors associated with successful hepatitis B vaccination. Thirty-four patients (17.5%) developed a protective antibody response. In a logistic regression model, only a plasma HIV RNA level of <400 copies/mL at the time of vaccination was associated with a protective antibody response (P=.003).

Manosuthi W, Chumpathat N, Chaovavanich A, Sungkanuparph S. · Bamrasnaradura Institute, Ministry of Public Health, Nonthaburi, 11000, Thailand. · BMC Infect Dis. · Pubmed #16120209 links to  free full text

Abstract: BACKGROUND: To compare the adverse events after initiation of NVP-based ART among HIV-infected patients who did not receive fluconazole (group A), received fluconazole 400 mg/week (group B), and received fluconazole 200 mg/day (group C). METHODS: A retrospective cohort study was conducted among HIV-infected patients who began NVP-based ART between December 2003 and September 2004. Patients were followed up for 6 months. Clinical hepatitis, elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (> 3 times from baseline), and skin rashes were studied. RESULTS: There were 686 patients; 225, 392, and 69 patients in group A, B, and C, respectively. Baseline characteristics including age, previous opportunistic infections, use of antituberculous drugs, and baseline aminotransferase levels among the three groups were similar. Group C had a higher proportion of men (p = 0.016). Baseline median (IQR) CD4 cell counts were 85 (21-159), 18 (7-48), and 16 (5-35) cell/mm3 in group A, B, and C, respectively (p < 0.001). Of 2/225 (0.9%), 4/392 (1.0%), and 0/69 (0%) patients in group A, B, and C developed clinical hepatitis (p = 0.705). There were no significant difference of elevated AST or ALT among the three groups (p > 0.05). By logistic regression, receiving fluconazole was not predictive of clinical hepatitis, elevated aminotransferase, or skin rashes. At 6 months after initiating NVP, 174 (77.3%) patients in group A, 309 (78.8%) patients in group B, and 58 (84.1%) patients in group C remained on NVP. CONCLUSION: Initiation of NVP-based ART among Thais with advance HIV disease receiving fluconazole is safe and well-tolerated. NVP should not be contraindicated for patients receiving fluconazole for treatment or prophylaxis of cryptococcosis.

Sungkanuparph S, Vibhagool A, Manosuthi W, Kiertiburanakul S, Atamasirikul K, Aumkhyan A, Thakkinstian A. · Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. · J Med Assoc Thai. · Pubmed #15825712 No free full text.

Abstract: BACKGROUND: Hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV share the route of transmission. HBV or HCV co-infection with HIV has been associated with a reduced survival rate, an increased risk of progression to severe liver disease, and an increased risk of hepatotoxicity associated with active antiretroviral therapy. Information regarding prevalence of HBV and HCV co-infection with HIV in Thailand is limited. PATIENTS AND METHOD: A cross-sectional study of prevalence and risk factors of HBV and HCV co-infection in HIV-infected patients was conducted. All HIV-infected patients who were cared for in March 2003 at Ramathibodi Hospital were included. RESULTS: There were 529 HIV-infected patients with a mean age of 36.7 years and 56.5% males. Of these, 58.8% lived in Bangkok, whereas, the others were from provincial areas. Heterosexual contact were the acquisition of HIV infection in 98.1% of all patients. The prevalence of HBV infection was 8.7%, and HCV infection was 7.8%. There was no difference between the prevalence of these infections in Bangkok and provincial areas (p = 0.115). History of intravenous drug use was associated with both HBV and HCV co-infection (p < 0.001). HCV co-infection group was also associated with male gender (p = 0.002) and elevated serum alanine transaminase (ALT) level (p = 0.0003). CONCLUSIONS: The prevalence of HBV and HCV co-infection with HIV in Thai patients is significant. In the author s resources-limited setting, history of intravenous drug use is a major indicator to screen for both HBV and HCV co-infection. Male gender and elevated serum ALT level are also suggestive of HCV co-infection.