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

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

<p>Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.</p> <p>Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.</p> <p>Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].</p> <p>Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.</p&gt

Current progress in the prevention of mother-to-child transmission of hepatitis B and resulting clinical and programmatic implications

There is currently no cure for hepatitis B chronic infections. Because new hepatitis B infections result mainly from perinatal transmission, preventing mother-to-child transmission is essential to reach by 2030 the goal of hepatitis B elimination set by the World Health Organization. The universal administration of hepatitis B vaccine to all infants, regardless of maternal status, starting with the birth dose, is the cornerstone of the strategy for elimination. Additional interventions, such as hepatitis B immune globulin administered to newborns and antiviral prophylaxis administered to hepatitis B infected pregnant women, may contribute to reaching the goal earlier. Hepatitis B immune globulin may remain out for reach of many pregnant women in low-and middle-income countries due to cost and logistic issues, but antivirals are cheap and do not require a cold chain for distribution. However, it has been observed that some viruses harbor mutations associated with escape from vaccine-elicited antibodies following immunization or administration of hepatitis B immune globulin. Also, resistance associated mutations have been described for several drugs used for treatment of hepatitis B infected patients as well as for the prevention of mother-to-child transmission. Whether these mutations have the potential to compromise the prevention of mother-to-child transmission or future treatment of the mother is a question of importance. We propose a review of important recent studies assessing tenofovir disoproxil fumarate for the prevention of mother-to-child transmission, and provides detailed information on the mutations possibly relevant in this setting

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 log(10)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 log(10)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

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

HIV RNA measurement in dried blood spots of HIV-infected patients in Thailand using Abbott m2000 system

World Health Organization recommends using dried blood spots (DBS) for HIV RNA viral load (VL) measurement whenever plasma processing is not convenient or feasible. DBS collected from 80 treatment-naive HIV-infected patients presenting in three hospitals of two different regions of Thailand were shipped to a central laboratory along with corresponding plasma specimens. Viral load was measured in both DBS and plasma using the Abbott m2000 system. HIV RNA levels were strongly correlated (r = 0.94) with a mean of differences of 0.23 log(10) copies/mL. Using the 1,000 copies/mL cut-off, the sensitivity of DBS was 97% (95%CI, 91-100%) and specificity was 75% (95%CI, 19-99%). DBS are useful to scale-up HIV RNA VL testing in settings with limited access to VL testing

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

Serologic characteristics of hepatitis B virus among hill-tribe children in Omkoi district, Chiangmai province, Thailand

Introduction: Thailand has integrated hepatitis B (HB) vaccination of newborns into the national Expanded Program on Immunization (EPI) in 1992. This has led to a dramatic decrease of HBsAg prevalence in children. However, HB vaccine coverage in remote areas is not well-known. This study aimed to investigate serologic characteristics of hepatitis B virus (HBV) among hill-tribe children in Omkoi District, Chiangmai Province, Thailand. Methodology: This cross-sectional study was conducted on stored samples collected from hill-tribe children attending the primary/secondary school in Omkoi District in December 2014. Sera were tested for HBsAg, anti-HBs and anti-HBc using enzyme immunoassays (MUREX, DiaSorin, Italy). Samples with anti-HBc positive were further assessed for HBV DNA using an in-house HBV DNA semi-nested polymerase chain reaction (PCR) assay. Results: Of 210 children evaluated, 4 (1.9%:95% CI 0.5-4.8) were HBsAg-positive. Of the 206 children HBsAg negative, 17 were anti-HBc and anti-HBs positive, 15 anti-HBc positive only, 26 anti-HBs positive only and 148 negative for both anti-HBc and anti-HBs. None of the children with anti-HBc were positive for HBV DNA. Conclusions: A high percentage of children had no markers of HBV protection suggesting that HB vaccine coverage was not optimal in this area. Our results warrant HBV serologic investigations in other remote areas to assess whether HB vaccine coverage needs to be improved and to identify children who should be vaccinated