Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia.

OBJECTIVE: Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. METHODS: Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. RESULTS: Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. CONCLUSIONS: This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support

Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia

Background: Multi-nucleos(t)ide resistance (MNR) mutations including Q151M, K65R mutations, and insertion at codon 69 of HIV-1 reverse transcriptase coding region may confer resistance to all molecules of nucleos(t)ide reverse transcriptase inhibitors (NRTI). The presence of these mutations is an emerging problem compromising non-nucleoside reverse transcriptase inhibitors and protease inhibitors-based therapies. Furthermore, factors associated with selection of these mutations are still not well defined. The current study aimed to evaluate the frequency and to characterize factors associated with the occurrence of multi-nucleos(t)ide resistance mutations among HIV-1 infected patients failing recommended first-line antiretroviral regimens in Cambodia. Methodology/Principal Finding: This is a retrospective analysis of HIV-1 drug resistance genotyping of 520 HIV-1 infected patients in virological failure (viral load > 250 copies/mL) while on first-line antiretroviral therapy in Cambodia with at least one reverse transcriptase inhibitor resistance associated mutation. Among these 520 patients, a total of 66 subjects (66/520, 12.7%) presented >= 1 MNR mutation, including Q151M, K65R, and Insert69 for 59 (11.3%), 29 (5.6%), and 2 (0.4%) patients, respectively. In multivariate analysis, both Q151M (p = 0.039) and K65R (p = 0.029) mutations were independently associated with current stavudine-compared to zidovudine-use. Conclusion: Such selection of mutations by stavudine drastically limits the choice of antiretroviral molecules available for second-line therapy in resource-limited settings. This finding supports the World Health Organization's recommendation for stavudine phase-out

Analytical and field evaluation of the Biocentric Generic HCV assay on open polyvalent PCR platforms in France and Cambodia

International audienceBackground: Implementation of affordable methods for HCV viremia is a key priority for identifying individuals who need treatment among persons screened positive for HCV antibodies. Different HCV PCR assays for use on open polyvalent PCR platforms are currently commercially available but studies evaluating the performances of these nucleic acid tests are needed. Objectives: In the present study, we evaluated the analytical and clinical performances of a recently developed HCV RNA PCR assay for detection and quantification of HCV viremia. Results: The lower limit of detection ranged from 50 HCV RNA IU/ml to 300 HCV RNA IU/ml using four different Diasorin and Qiagen automated or manual extraction methods. The specificity (CI) and sensitivity of the assay were 100% (92.5-100), and 98.7% (92.3-99.9), respectively, in France, and 100% (95.5-100), and 100% (94.4-100%), respectively, in Cambodia. Bland-Altman analysis shown good agreement between the two assays including for genotypes 6 HCV, which represent the majority of HCV isolates in Cambodia. Conclusions: The Biocentric Generic HCV assay has shown overall satisfactory analytical performances and a close agreement to the Cobas HCV assay on clinical specimens collected in France and Cambodia. There is an urgent need to further evaluate commercial assays dedicated to HCV detection and quantification using open polyvalent PCR platforms in different settings

Declining hepatitis E virus antibody prevalence in Phnom Penh, Cambodia during 1996–2017

International audienceHepatitis E virus (HEV) infection is endemic in Cambodia. However, little relevant data were available and there is no clue if HEV is an emerging or decreasing pathogen in that setting. The aim of our study was to describe temporal trends of anti-HEV IgG and IgM prevalences during the last two decades (1996–2017) in the context of population growth and urbanisation in Cambodia. A total of 2004 human plasma samples collected between 1996 and 2017 were tested for anti-HEV IgG and IgM using the commercial Wantai anti-HEV assays. Overall, the prevalences of anti-HEV IgG and IgM were 41.1% and 2.7%, respectively. Analysis by calendar period showed a decreasing trend of anti-HEV IgG prevalence over the last 21 years. After age- and gender-standardisation, the anti-HEV IgG prevalence rates decreased from 61.3% during the 1996–2000 period to 32.3% during the 2016–2017 period, but no trends were observed for anti-HEV IgM rates, which fluctuated around the overall one. In conclusion, our results suggest that HEV is not an emerging pathogen, but rather seems to circulate less in Cambodia, in particular, in Phnom Penh, since the prevalence of anti-HEV IgG has been significantly decreased during the past two decades

MOLECULAR EPIDEMIOLOGY AND SEROPREVALENCE OF CARDAMONES VARIANT WENZHOU VIRUS IN RODENTS AND HUMANS IN CAMBODIA

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Predictive value of anti-cell and anti-human immunodeficiency virus (HIV) humoral responses in HIV-1-exposed seronegative cohorts of European and Asian origin.

International audienceUnconventional immune responses have been demonstrated in individuals who, despite repeated exposure to human immunodeficiency virus (HIV) infection, remain seronegative. As environmental exposure to pathogens and genetic background may modulate immune responses differentially, one Italian and two Asian populations of HIV-1-exposed seronegative individuals were studied. In serum samples from each group, IgG to CCR5, IgG to CD4 and IgA to gp41 were measured, which were previously described as markers of unconventional immunity in HIV-exposed seronegative Caucasians. Given the importance of conformational epitopes in virus-cell interactions, IgG to CD4-gp120 complex was also measured. It was found that markers of HIV exposure were present in all populations studied. HIV-specific humoral responses (IgA to gp41 and IgG to CD4-gp120 complex) were extremely significant predictors of HIV exposure (P<0.0001 in both cases), whereas the predictive values of anti-cell antibodies (anti-CCR5 and anti-CD4) varied between populations. Evidence is provided for the correlation of these differences with route of exposure to HIV and level of natural antibodies to cross-reactive microbial antigens. In conclusion, exposed seronegative individuals of ethnically different origins display similar signs of HIV-dependent unconventional immunity. A specific relevance must be attributed to different innate and acquired factors

Usefulness of a serial algorithm of HBsAg and HBeAg rapid diagnosis tests to detect pregnant women at risk of HBV mother-to-child transmission in Cambodia, the ANRS 12328 pilot study

Background: In Cambodia, access to hepatitis B surface antigen (HBsAg) screening is low for pregnant women and Hepatitis B Virus (HBV) DNA quantification is poorly accessible. Objectives: To evaluate the performance of a serial algorithm using two HBV rapid diagnostic tests (RDTs), in which samples positive for HBsAg were further tested for HBeAg as a surrogate marker for HBV DNA quantification. Study design: In 2015, we prospectively collected plasma samples from 250 pregnant women consulting for antenatal care in one hospital in Phnom Penh including 128 with a known positive HBsAg status. All specimens were tested with the SD BIOLINE HBsAg RDT and HBsAg ELISA assay. In ELISA-positive samples, HBeAg status was determined using the SD BIOLINE HBeAg RDT and HBV DNA quantification was assessed. Results: Sensitivity and specificity of HBsAg RDT were 99.2% (97.7-99.9) and 100% (97.0-100), respectively. Among the 128 ELISA-positive samples, 29 (23%) tested HBeAg positive and 34 (26.5%) had HBV DNA > 5.3 Log(10) IU/mL. Sensitivity and specificity of HBeAg RDT in identifying viremic samples were 76.5% (62.2.0-90.7) and 96.8% (93.3-100) for HBV DNA > 5.3 Log(10) IU/mL and 89.3% (77.8-100) and 96.0% (92.2-99.8) for HBV DNA > 7.3 Log(10) IU/mL. Among the 99 negative HBeAg RDT women, 8 had HBV DNA > 5.3 Log10 IU/mL and 7 of them harbored BCP/PC HBV mutants. Conclusions: A combination of HBsAg and HBeAg RDTs could be a low-cost strategy to identify HBV-infected pregnant women at risk of perinatal transmission in a country were HBV DNA quantification is not routinely available