Woottichai Khamduang

Prevalence, Risk Factors, and Impact of Isolated Antibody to Hepatitis B Core Antigen and Occult Hepatitis B Virus Infection in HIV-1–Infected Pregnant Women

BACKGROUND Prevalence and risk factors for isolated antibody to hepatitis B core antigen (anti-HBc) and occult hepatitis B virus (HBV) infection are not well known in human immunodeficiency virus type 1 (HIV-1)-infected pregnant women. It is unclear if women with occult infections are at risk of transmitting HBV to their infants. METHODS HIV-1-infected and HBV surface antigen (HBsAg)-negative pregnant women were tested for antibody to HBsAg (anti-HBs) and anti-HBc using enzyme immunoassay. Women with isolated anti-HBc were assessed for occult HBV infection, defined as HBV DNA levels >15 IU/mL, using the Abbott RealTime HBV DNA assay. Infants born to women with isolated anti-HBc and detectable HBV DNA were tested at 4 months of age for HBV DNA. Logistic regression analysis was used to identify factors associated with isolated anti-HBc and occult HBV infection. RESULTS Among 1812 HIV-infected pregnant women, 1682 were HBsAg negative. Fourteen percent (95% confidence interval [CI], 12%-15%) of HBsAg-negative women had an isolated anti-HBc that was independently associated with low CD4 count, age >35 years, birth in northern Thailand, and positive anti-hepatitis C virus serology. Occult HBV infection was identified in 24% (95% CI, 18%-30%) of women with isolated anti-HBc, representing 2.6% (95% CI, 1.9%-3.5%) of HIV-1-infected pregnant women, and was inversely associated with HIV RNA levels. None of the women with isolated anti-HBc and occult HBV infection transmitted HBV to their infants. CONCLUSIONS HIV-1-infected pregnant women with isolated anti-HBc and occult HBV infection have very low HBV DNA levels and are thus at very low risk to transmit HBV to their infants.

Human immunodeficiency virus–hepatitis C virus co-infection in pregnant women and perinatal transmission to infants in Thailand

OBJECTIVES The objectives of this study were to assess the prevalence and factors associated with hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected and -uninfected Thai pregnant women and the rate of HCV transmission to their infants. PATIENTS AND METHODS Study subjects included 1435 HIV-infected pregnant women and their infants, enrolled in a perinatal HIV prevention trial, and a control group of 448 HIV-uninfected pregnant women. Women were screened for HCV antibodies with an enzyme immunoassay. Positive results were confirmed by recombinant immunoblot and HCV RNA quantification. Infants were tested for HCV antibodies at 18 months or for HCV RNA at between 6 weeks and 6 months. RESULTS Of the HIV-infected women, 2.9% were HCV-infected compared to 0.5% of HIV-uninfected women (p=0.001). Only history of intravenous drug use was associated with HCV infection in HIV-infected women. Ten percent of infants born to co-infected mothers acquired HCV. The risk of transmission was associated with a high maternal HCV RNA (p=0.012), but not with HIV-1 load or CD4 count. CONCLUSIONS Acquisition of HCV through intravenous drug use partially explains the higher rate of HCV infection in HIV-infected Thai women than in HIV-uninfected controls. Perinatal transmission occurred in 10% of infants of HIV-HCV-co-infected mothers and was associated with high maternal HCV RNA.

Long-Term Hepatitis B Virus (HBV) Response to Lamivudine-Containing Highly Active Antiretroviral Therapy in HIV-HBV Co-Infected Patients in Thailand

Background Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART) and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known. Methodology/Principal Finding HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log10 IU/mL and 4.47 log10 copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months). HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L. Conclusions All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of co-infected patients in resource-limited countries where the vast majority of co-infected patients are currently receiving 3TC.

Prevalence of chronic hepatitis B virus infection in Thailand: a systematic review and meta-analysis.

OBJECTIVE To estimate the number of people living in Thailand with chronic hepatitis B (CHB), a major cause of liver cirrhosis and cancer, in view of the implementation of programs to prevent CHB complications. METHODS Using PubMed/Medline and ScienceDirect, all studies reporting hepatitis B surface antigen (HBsAg) seroprevalence estimates conducted in Thailand and published between 1975 and 2015 were reviewed systematically. Pooled prevalence estimates and their 95% confidence intervals (CIs) were calculated, and potential sources of heterogeneity investigated. RESULTS A high heterogeneity was observed between prevalence estimates. There was a significant decrease in the 150 estimates of HBsAg prevalence with more recent decades of birth (p<0.001), even before the implementation of the national universal immunization program in 1992. When restricted to the general population, the pooled prevalence estimate was 5.1% (95% CI 4.3-6.0%), which would translate to an estimated number of individuals with CHB living in Thailand in 2015 as high as three million. CONCLUSIONS The high burden of CHB in Asian countries is a major challenge for the incorporation of national programs to prevent CHB complications within health care systems.

Early infant HIV diagnosis and entry to HIV care cascade in Thailand: an observational study

BACKGROUND Early infant diagnosis of HIV is crucial for timely initiation of antiretroviral therapy (ART) in infected children who are at high risk of mortality. Early infant diagnosis with dried blood spot testing was provided by the National AIDS Programme in Thailand from 2007. We report ART initiation and vital status in children with HIV after 7 years of rollout in Thailand. METHODS Dried blood spot samples were collected from HIV-exposed children in hospitals in Thailand and mailed to the Faculty of Associated Medical Sciences, Chiang Mai University, where HIV DNA was assessed with real-time PCR to establish HIV infection. We linked data from children with an HIV infection to the National AIDS Programme database to ascertain ART and vital status. FINDINGS Between April 5, 2007, and Oct 1, 2014, 16 046 dried blood spot samples were sent from 8859 children in 364 hospitals in Thailand. Median age at first dried blood spot test was 2·1 (IQR 1·8-2·5) months. Of 7174 (81%) children with two or more samples, 223 (3%) were HIV positive (including five unconfirmed). Of 1685 (19%) children with one sample, 70 (4%) were unconfirmed positive. Of 293 (3%) children who were HIV positive, 220 (75%) registered for HIV care and 170 (58%) initiated ART. Median age at ART initiation decreased from 14·2 months (IQR 10·2-25·6) in 2007 to 6·1 months (4·2-9·2) in 2013, and the number of children initiating ART aged younger than 1 year increased from five (33%) of 15 children initiating ART in 2007 to ten (83%) of 12 initiating ART in 2013. 15 (9%) of 170 children who initiated ART died and 16 (32%) of 50 who had no ART record died. INTERPRETATION Early infant diagnosis with dried blood spot testing had high uptake in primary care settings. Further improvement of linkage to HIV care is needed to ensure timely treatment of all children with an HIV infection. FUNDING None.

Potential Missed Opportunities Related to the Systematic Screening for Hepatitis B Surface Antigen in Thailand

Background: In Thailand, hepatitis B surface antigen (HBsAg) testing is part of routine antenatal screening. We assessed the association between characteristics of pregnant women attending Samut Prakan Provincial Hospital antenatal care clinic (ANC) and their Hepatitis B virus (HBV) infection status. Methods: This is a cross-sectional study of pregnant women ≥ 18 yrs presenting at the ANC between August 1st, 2013 and June 30th, 2015. Data on socio-demographics, general physical examination, obstetrical and medical history and knowledge of HBV status were collected. Comparisons were performed using the Wilcoxon-Mann- Whitney test or Fisher’s exact test. Results: A total of 115 pregnant women, 18 HBsAg positive and 97 negative, participated. The women had a median age of 27.1 yrs (interquartile range (IQR): 22.4 to 31.5) at a median 28.0 weeks gestational age (IQR: 26.1 to 29.7). Forty-five (39%) reported being born abroad. Sixteen (14%) did not receive primary education. The women’s household contained a median of 3 persons (IQR: 2 to 4). None of these characteristics differed between HBsAg positive and negative women. HBsAg positive women were more likely to know their HBV status than HBsAg negative women [6 (33%)] vs. 12 [(12%), p=0.04] and their previous live offsprings’ HBV status [9 (60%)] vs. 21 [(26%), p=0.01]. In contrast, they were less likely to know their partner’s HBV status [3 (17%)] vs. 50 [(52%), p=0.009]. Conclusion: HBV chronic infection was not associated with any characteristics, which justifies systematic screening for HBsAg during antenatal care. The vast majority of women were not able to report their and their partner’s HBsAg status, underlining potential missed opportunities to be followed for their hepatitis B infection.

Development and validation of an oligonucleotide ligation assay to detect lamivudine resistance in hepatitis B virus

Treatment of chronic hepatitis B virus (HBV) infection with lamivudine-monotherapy rapidly selects mutant variants in a high proportion of individuals. Monitoring lamivudine resistance by consensus sequencing is costly and insensitive for detection of minority variants. An oligonucleotide ligation assay (OLA) for HBV lamivudine-resistance was developed and compared to consensus sequencing. Both assays detected drug resistance mutations in 35/64 (54.7%) specimens evaluated, and OLA detected minority mutants in an additional six (9.4%). OLA may offer a sensitive and inexpensive alternative to consensus sequencing for detection of HBV drug resistance in resource-limited settings.

Risk factors for HCV infection in HIV positive pregnant women and rate of HCV perinatal transmission in Thailand

Address: 1IRD 174/PHPT, Chiang Mai, Thailand, 2Chiang Mai University, Faculty of Associated Medical Sciences, Chiang Mai, Thailand, 3UMR 196 CEPED (INED-IRD-Universite Paris Descartes), Paris, France, 4Nakornping Hospital, Chiang Mai, Thailand, 5Lamphun Hospital, Lamphun, Thailand, 6Chiang Kham Hospital, Chiang Kham, Thailand and 7Laboratoire de Virologie, INSERM ERI 19, and Centre National de Reference pour le VIH, Universite F Rabelais, Tours, France * Corresponding author

Risk factors for human cytomegalovirus (HCMV) infection in infants born to HIV-1 infected mothers in Thailand

Address: 1Institut de Recherche pour le Developpement UMI 174/Programs for HIV Prevention and Treatment (PHPT), Chiang Mai, Thailand, 50100, 2Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand, 50200, 3Harvard School of Public Health, Harvard University, Boston, MA 02115, USA, 4Harvard Medical School, Harvard University, Boston, MA 02115, USA, 5Lamphun Hospital, Lamphun, Thailand, 51000, 6Health Promotion Hospital Regional Center I, Bangkok, Thailand, 10210, 7Somdej Pranangchao Sirikit Hospital, Chonburi, Thailand, 20000 and 8Buddhachinaraj Hospital, Pitsanuloke, Thailand, 65000 * Corresponding author