Knowledge, attitudes, practices and prevalence of hepatitis B and C and hepatitis B vaccination coverage among public sector healthcare workers in Cambodia.

Healthcare workers (HCWs) are a key population at high risk for hepatitis B (HBV) and hepatitis C (HCV) infections. We aim to study HBV vaccination coverage, seroprevalence, knowledge, attitudes, and practices towards HBV and HCV infections among HCWs in public sector in Cambodia. A nationally representative cross-sectional study was implemented in 2019, among Cambodian HCWs. A standardized questionnaire was administered to randomly selected HCWs whose blood was then sampled. We used univariate and multivariate regression to determine predictors of outcomes. Among 755 participants, we found 4.9% positive HBsAg and 2.3% positive anti-HCV Ab. HBV vaccination coverage was 59.3%. Lack of knowledge was found on the route of transmission, HBV vaccination, diagnosis and treatment of HBV and HCV. 67% of HCWs thought that all patients should be screened for HBV and HCV and about 30% of them would refuse to take care of infected patients. 58% of HCWs always recapped the needle after use. In univariate analysis, older age-group (> 50 years) is more likely to have positive anti-HCV (OR: 9.48; 95% CI: 2.36-38.18). HCWs who were younger, female or having higher education or having ever been tested, were more likely to have gotten HBV vaccinated. Multivariate analysis reconfirmed these predictors of getting vaccinated. Study findings indicated an urgent need of a national policy for Cambodian HCWs given the high prevalence of hepatitis among this group. Policy should include an effective in-service training program to improve knowledge and practices, a testing and vaccination program for HCWs and it should emphasize stigma intervention towards people living with HBV/HCV.

The continuing HIV epidemic among men who have sex with men and transgender women in the ASEAN region: implications for HIV policy and service programming.

Men who have sex with men (MSM) in Western urban areas have seen substantive decreases in new diagnoses of HIV infection. This paper explores whether such declines are present among MSM and transgender women (TGW) in Southeast Asia and discusses implications for HIV policies and programming. A scoping review was conducted of scientific publications and selected documents regarding the spread of HIV infection among MSM and TGW in major urban centres of the Association of Southeast Asian Nations (ASEAN) region. Continued high HIV prevalence and incidence among MSM are found in integrated behavioural and biological surveillance (IBBS) and research studies. HIV prevalence among MSM under IBBS decreased only in Bangkok from 28.6% in 2014 to 10.3% in 2018, whereas it was increasing in Kuala Lumpur, Ho Chi Minh City, Vientiane, and Phnom Penh. HIV/AIDS case reports regarding new HIV infection diagnoses among MSM have started to decrease in Singapore since 2011 and have been plateauing in Metropolitan Manila since 2017. Where data were available, it was found that HIV prevalence among TGW was high and if IBBS was conducted, it was increasing. HIV prevalence among TGW under IBBS in Jakarta had risen to 34.0% (2015) and 14.0% (2019) in Phnom Penh. These findings suggest that most ASEAN member states have so far failed to effectively implement and scale-up scientifically proven biomedical HIV prevention measures and counter stigma and discrimination that impedes access to appropriate HIV prevention and treatment services for MSM and TGW.

Access to prevention of mother-to-child transmission of HIV along HIV services cascade through integrated active case management in 15 operational districts in Cambodia.

INTRODUCTION: Following the introduction of option B+ in 2013, and with the perspective of eliminating mother-to-child transmission of HIV by 2025, Cambodia has implemented an integrated active case management (IACM) approach since 2014 to improve the notification and follow-up of all HIV-infected cases including pregnant women, and to ensure access to and use of the full prevention of mother-to-child transmission (PMTCT) service package by HIV-infected pregnant women and their HIV-exposed infants. This study aimed to analyse PMTCT cascade data in 15 operational districts (ODs) implementing the IACM approach in Cambodia. METHODS: We analysed PMTCT cohort data from 15 ODs implementing IACM approach between 1 January 2014 and 31 December 2016. We measured key indicators along the PMTCT cascade and compared them to available (cross-sectional) PMTCT indicators during the 2011 to 2013 period. RESULTS: During the period 2014 to 2016, among 938 identified HIV-infected pregnant women, 308 (32.8%) were tested HIV positive during their pregnancy, 9 (1.0%) during labour, while the remaining 621 (66.2%) were women on antiretroviral therapy (ART) who became pregnant. During the study period, 867 (92.4%) of the 938 women received ART during pregnancy and labour. Subsequently, 456 (85.6%) of the 533 HEI born and alive during the study period received 6-week antiretroviral (ARV) prophylaxis, 390 (76.6%) and 396 (77.8%) of the 509 infants aged six weeks or older received cotrimoxazole prophylaxis and HIV-DNA PCR test respectively. Among the 396 HEI who received HIV-DNA PCR test, 7 (1.8%) were found HIV positive. The comparison with cross-sectional PMTCT indicator obtained during the previous 2011 to 2013 period in the same 15 ODs, showed a significant increase in ARV uptake among HIV-infected pregnant women (from 72.3% to 92.4%), in cotrimoxazole uptake (from 41.6% to 73.2%), and in HIV-DNA PCR testing coverage among HEI (from 41.2% to 74.3%). CONCLUSIONS: The implementation of option B+ and IACM may have contributed to the improvement of the PMTCT cascade in Cambodia. However, some gaps in accessing PMTCT services along the HIV cascade persist and need to be addressed.

Integrated approach for triple elimination of mother-to-child transmission of HIV, hepatitis B and syphilis is highly effective and cost-effective: an economic evaluation.

BACKGROUND: The Regional Framework for Triple Elimination of Mother-to-Child Transmission (EMTCT) of HIV, Hepatitis B (HBV) and Syphilis in Asia and the Pacific 2018-30 was endorsed by the Regional Committee of WHO Western Pacific in October 2017, proposing an integrated and coordinated approach to achieve elimination in an efficient, coordinated and sustainable manner. This study aims to assess the population impacts and cost-effectiveness of this integrated approach in the Cambodian context. METHODS: Based on existing frameworks for the EMTCT for each individual infection, an integrated framework that combines infection prevention procedures with routine antenatal care was constructed. Using decision tree analyses, population impacts, cost-effectiveness and the potential reduction in required resources of the integrated approach as a result of resource pooling and improvements in service coverage and coordination, were evaluated. The tool was assessed using simulated epidemiological data from Cambodia. RESULTS: The current prevention programme for 370,000 Cambodian pregnant women was estimated at USD$2.3 ($2.0-$2.5) million per year, including the duration of pregnancy and up to 18 months after delivery. A model estimate of current MTCT rates in Cambodia was 6.6% (6.2-7.1%) for HIV, 14.1% (13.1-15.2%) for HBV and 9.4% (9.0-9.8%) for syphilis. Integrating HIV and syphilis prevention into the existing antenatal care framework will reduce the total time required to provide this integrated care by 19% for health care workers and by 32% for pregnant women, resulting in a net saving of $380,000 per year for the EMTCT programme. This integrated approach reduces HIV and HBV MTCT to 6.1% (5.7-6.5%) and 13.0% (12.1-14.0%), respectively, and substantially reduces syphilis MCTC to 4.6% (4.3-5.0%). Further introduction of either antiviral treatment for pregnant women with high viral load of HBV, or hepatitis B immunoglobulin (HBIG) to exposed newborns, will increase the total cost of EMTCT to $4.4 ($3.6-$5.2) million and $3.3 ($2.7-$4.0) million per year, respectively, but substantially reduce HBV MTCT to 3.5% (3.2-3.8%) and 5.0% (4.6-5.5%), respectively. Combining both antiviral and HBIG treatments will further reduce HBV MTCT to 3.4% (3.1-3.7%) at an increased total cost of EMTCT of $4.5 ($3.7-$5.4) million per year. All these HBV intervention scenarios are highly cost-effective ($64-$114 per disability-adjusted life years averted) when the life benefits of these prevention measures are considered. CONCLUSIONS: The integrated approach, using antenatal, perinatal and postnatal care as a platform in Cambodia for triple EMTCT of HIV, HBV and syphilis, is highly cost-effective and efficient.

Positive Virological Outcomes of HIV-Infected Patients on Protease Inhibitor-Based Second-Line Regimen in Cambodia: The ANRS 12276 2PICAM Study.

BACKGROUND: Assessment of virological outcomes among HIV-infected patients receiving protease (PR) inhibitor-based second-line regimen are uncommon in Cambodia. The objective of this study is to assess the virological effectiveness of this regimen as well as impact of adherence boosting for patients experiencing virological failure. METHODS: The 2PICAM study (Clinicaltrial: NCT01801618) is a cross-sectional study of HIV-infected adults on PR inhibitor-based second-line regimen since at least 6 months, conducted in 13 representative sites, comprising more than 90% of the target population. Adults with HIV RNA above 250 copies/mL (threshold of the assay) at inclusion received boosted adherence counseling during 3 months followed by HIV RNA control. For confirmed virological failure, genotype resistance test was performed and expert committee used results for therapeutic decision. RESULTS: Among the 1,317 adults enrolled, the median duration of second-line regimen was 5 years. At inclusion, 1,182 (89.7%) patients achieved virological success (<250 copies/mL) and 135 (10.3%) experienced a virological failure (>250 copies/mL). In multivariable analysis, factors associated with virological success were: CD4 cell count between 201 and 350/mm3 (OR: 4.66, 95% CI: 2.57-8.47, p < 0.0001) and >350/mm3 (OR: 6.67, 95% CI: 4.02-11.06, p < 0.0001), duration of PI-based regimen >2 years (OR: 1.64, 95% CI: 1.03-2.62, p = 0.037), ATV-containing regimen (0R: 1.65, 95% CI: 1.04-2.63, p = 0.034) and high level of adherence (OR: 2.41, 95% CI: 1.07-5.41, p = 0.033). After adherence counseling, 63 (46.7%) patients were rescued while 72 (53.3%) were not. For the 54 patients with genotype resistance tests available, high or intermediate levels of resistance to lopinavir, atazanavir, and darunavir were reported for 13 (24%), 12 (22.2%), and 2 (3.7%) patients, respectively. Change to an alternative PR inhibitor-based regimen was recommended for 17 patients and to third-line regimen, including integrase inhibitors for 12. CONCLUSION: This study reports high rate of virological suppression of second-line regimen and importance of adherence boosting prior to deciding any change of ART regimen. Genotype resistance tests appear necessary to guide decisions. Such information was of great importance for National HIV Program to adapt guidelines and program needs for third-line regimen.

Massive Iatrogenic Outbreak of Human Immunodeficiency Virus Type 1 in Rural Cambodia, 2014-2015.

Background: In 2014-2015, 242 individuals aged 2-89 years were newly diagnosed with human immunodeficiency virus type 1 (HIV-1) in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak. Methods: We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C virus (HCV) and hepatitis B virus (HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV. We performed amplification, sequencing, and evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed healthcare practitioner were obtained from 193 cases and 1499 controls during interviews. Results: Cases were coinfected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent (<130 days) HIV infections. Phylogeny of 202 HIV env C2V3 sequences showed a 198-sample CRF01_AE strains cluster, with time to most recent common ancestor (tMRCA) in September 2013 (95% highest posterior density, August 2012-July 2014), and a peak of 15 infections/day in September 2014. Three geospatial HIV hotspots were discernible in Roka and correlated with high exposure to the practitioner (P = .04). Fifty-nine of 153 (38.6%) tested cases showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed 3 main clades, 1 containing 34 subtypes 1b with tMRCA in 2012, and 2 with 51 subtypes 6e and tMRCAs in 2002-2003. Conclusions: Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically diverse HCV propagation.

Adherence to PI-based 2nd-line regimens in Cambodia is not simply a question of individual behaviour: the ANRS 12276 2PICAM study.

OBJECTIVES: To investigate whether adherence to antiretroviral treatment (ART) can be explained not only by individual factors but also by health care facilities' characteristics, among a sample of people living with HIV (PLWH) treated with PI-based regimens in Cambodia. METHODS: The ANRS 12276 2PICAM cross-sectional survey was conducted between February 2013 and April 2014 among PLWH followed up in 13 health care facilities. The 1316 patients in this analysis corresponded to 90% of the total number of adult patients treated with 2nd-line PI-based regimens in Cambodia in the study period. A variable indicating whether patients were non-adherent (=1) or completely adherent (=0) was constructed. Health care facilities and individual characteristics were included in a two-level logistic model to investigate their influence on patients' adherence to ART. RESULTS: A total of 17% of participants did not adhere to ART. Patients in health care facilities outside the capital Phnom Penh were six times more likely to be non-adherent than those treated in health care facilities in the capital (OR: 6.15, 95% CI [1.47, 25.79]). Providing psychosocial care (provided by psychologist counsellors and/or full-time coaches) was found to be a structural facilitator of adherence, as the probability of non-adherence fell by 38.5% per each additional psychological worker present in health care facilities (OR: 0.62, 95% CI [0.43, 0.89]). Financial constraints were the main individual factor preventing adherence. CONCLUSIONS: Our results suggest that inefficiencies in health care delivery are detrimental to PLWH health and to the exceptional progress currently being made by Cambodia in response to HIV. Policy makers should focus on increasing the number of psychosocial workers, especially in areas outside the capital.

HIV Prevalence and Risks Associated with HIV Infection among Transgender Individuals in Cambodia.

INTRODUCTION: Recognizing transgender individuals have a high risk of HIV acquisition, and to inform policies and programming, we conducted an HIV prevalence and risk behaviors survey among transgender individuals in Cambodia. METHODS: Cross-sectional survey using a respondent driven sampling method with self-administered audio-computer assisted interviews. HIV testing was performed prior to the questionnaire with results available immediately after. Eligible participants were ≥18 years, identified as male at birth and self-identified/expressed as a different gender, and reported having sex with at least one male partner in past year. From six major urban centers of Cambodia, 891 transgender individuals were recruited. RESULTS: The majority of the 891 participants self-identified as third gender or female (94.5%), were young (median age 23, IQR [20-27]), had secondary education or higher (80.5%), not married (89.7%), and employed (90.2%). The majority had first sex before 18 years (66.8%), with a male (79.9%), 37.9% having been paid or paying for this first sex. The rate of HIV positivity among participants was found to be 4.15%. Consistent condom use with male and female partners was low with all partner types, but particularly low with male partners when paying for sex (20.3%). The majority of participants reported having experienced discrimination in their lifetime (54.8%) and 30.3% had been assaulted. Multivariate analysis revealed that older age (adjusted OR = 14.73 [4.20, 51.67] for age 35-44 and adjusted OR = 7.63 [2.55, 22.81] for age 30-34), only having a primary school education or no schooling at all (adjusted OR = 2.62 [1.18, 5.80], being a resident of Siem Reap (adjusted OR = 7.44 [2.37, 23.29], receiving payment at first sex (adjusted OR = 2.26 [1.00, 5.11], having sex during/after using drugs (adjusted OR = 2.90 [1.09, 7.73]), inconsistent condom use during last anal sex (adjusted OR = 3.84 [1.58, 9.33]), and reporting low self-esteem (adjusted OR = 3.25 [1.35, 7.85]) were independently associated with HIV infection. CONCLUSIONS: This study confirms transgender individuals as one of the highest-risk groups for HIV infection in Cambodia. It suggests the need for programmatic strategies that mitigate identified associated risks and facilitate access to HIV care for this population.

Implementation and Operational Research: Integration of Family Planning Services in a Peer-Managed HIV Care Clinic Serving Most-at-Risk Populations in Phnom Penh, Cambodia.

OBJECTIVE: To assess contraceptive uptake and method choice among women living with HIV (WLHIV) attending an HIV care clinic serving most-at-risk women in Phnom Penh, Cambodia, before and after the implementation of family planning (FP) services. METHODS: Semistructured questionnaires were administered to clients before (July, 2011) and after (July, 2012) FP service implementation with provision of contraceptive methods (pills, injectables, implants, and intrauterine device [IUD]). RESULTS: Among 250 and 249 clients interviewed before and after implementation respectively, 24.5% of women reported selling sex for money during the last 6 months before and 35.3% after implementation. Awareness about contraceptive methods significantly increased among clients postimplementation. Among sexually active women, male condom remained the contraceptive method of choice with an overall condom use during the last 6 months at 91% postimplementation vs. 95.6% preimplementation (P = 0.11). Although the use of noncondom FP methods increased but not significantly (16.4% after vs. 12.6% before implementation, P = 0.8), the use of dual method (condom plus another method) remained low and did not significantly increase after implementation (14.8% after vs. 11.0% before, P = 0.28). CONCLUSIONS: Our results show that FP practices of WLHIV attending an HIV care clinic for most-at-risk populations did not significantly change after integration on-site provision of a wide range of FP methods. Innovative strategies and further research are needed to better understand how to promote the use of noncondom FP methods and prevent unwanted pregnancies and abortions among most-at-risk women and WLHIV.

Achieving universal access and moving towards elimination of new HIV infections in Cambodia.

INTRODUCTION: In the mid-1990s, Cambodia faced one of the fastest growing HIV epidemics in Asia. For its achievement in reversing this trend, and achieving universal access to HIV treatment, the country received a United Nations millennium development goal award in 2010. This article reviews Cambodia's response to HIV over the past two decades and discusses its current efforts towards elimination of new HIV infections. METHODS: A literature review of published and unpublished documents, including programme data and presentations, was conducted. RESULTS AND DISCUSSION: Cambodia classifies its response to one of the most serious HIV epidemics in Asia into three phases. In Phase I (1991-2000), when adult HIV prevalence peaked at 1.7% and incidence exceeded 20,000 cases, a nationwide HIV prevention programme targeted brothel-based sex work. Voluntary confidential counselling and testing and home-based care were introduced, and peer support groups of people living with HIV emerged. Phase II (2001-2011) observed a steady decline in adult prevalence to 0.8% and incidence to 1600 cases by 2011, and was characterized by: expanding antiretroviral treatment (coverage reaching more than 80%) and continuum of care; linking with tuberculosis and maternal and child health services; accelerated prevention among key populations, including entertainment establishment-based sex workers, men having sex with men, transgender persons, and people who inject drugs; engagement of health workers to deliver quality services; and strengthening health service delivery systems. The third phase (2012-2020) aims to attain zero new infections by 2020 through: sharpening responses to key populations at higher risk; maximizing access to community and facility-based testing and retention in prevention and care; and accelerating the transition from vertical approaches to linked/integrated approaches. CONCLUSIONS: Cambodia has tailored its prevention strategy to its own epidemic, established systematic linkages across different services and communities, and achieved nearly universal coverage of HIV services nationwide. Still, the programme must continually (re)prioritize the most effective and efficient interventions, strengthen synergies between programmes, contribute to health system strengthening, and increase domestic funding so that the gains of the previous two decades are sustained, and the goal of zero new infections is reached.

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.

Cytomegalovirus viremia in Thai HIV-infected patients on antiretroviral therapy: prevalence and associated mortality.

BACKGROUND: Prevalence and risk factors of cytomegalovirus (CMV) viremia in patients infected with human immunodeficiency virus (HIV) starting antiretroviral therapy (ART) in developing countries are understudied. METHODS: We measured CMV DNA in stored plasma specimens of 293 Thai HIV patients starting ART at CD4 counts <200 cells/mm(3). We examined Cox proportional hazard ratios (HRs) of 24 months mortality and new AIDS-defining illness (ADI). RESULTS: Of 293 patients, 159 (54.3%) were male. The median age was 33 years. The median baseline CD4 count was 82 cells/mm(3), and the median HIV-1 RNA was 4.9 log10 copies/mL. In total, 273 (93.2%) patients started potent combination ART, and 20 (6.8%) started dual nucleoside reverse transcriptase inhibitor (NRTI) therapy. CMV DNA was detected in 77 of 293 patients (26.3%) at baseline, and 9 of 199 patients with available specimen (4.5%) after 6 months of ART. The median CMV DNA was 548 copies/mL (interquartile range [IQR], 129-3849) at baseline and 114 copies/mL (IQR, 75-1099) at 6 months. In univariate analysis, death was associated with baseline CDC stage C, hemoglobin <10 g/dL, lower CD4 count, and CMV viremia. In multivariate analysis, only CMV DNA >500 copies/mL was significantly associated with mortality (HR: 7.28; 95% CI, 1.32-40.29, P = .023). CD4 count was the only variable associated with new ADI (HR: 0.70 per 50 CD4 cells increase; 95% CI, .49-.997, P = .048). CONCLUSIONS: In these Thai patients with advanced HIV disease, CMV viremia was frequent, and CMV DNA >500 copies/mL predicted increased mortality despite ART initiation. This calls for increased attention to screening of active CMV infection in advanced HIV patients in developing countries. Trials assessing preemptive anti-CMV therapy may be warranted.

High efficacy of lopinavir/r-based second-line antiretroviral treatment after 24 months of follow up at ESTHER/Calmette Hospital in Phnom Penh, Cambodia.

BACKGROUND: The number of patients on second-line highly active antiretroviral therapy (HAART) regimens is increasing in resource-limited settings. We describe the outcomes after 24 months for patients on LPV/r-based second-line regimens followed up by the ESTHER programme in Phnom Penh, Cambodia. METHODS: Seventy patients who initiated second-line HAART regimens more than 24 months earlier were included, and immuno-virological data analyzed. HIV RNA viral load was determined by real-time RT-PCR. HIV-1 drug resistance was interpreted according to the ANRS algorithm. RESULTS: Of the 70 patients, two were lost to follow up, three died and 65 (92.8%) remained on second-line treatment after 24 months of follow up (median duration of treatment: 27.4 months). At switch to second-line, the median CD4 T cell count was 106 cells/mm³ and the median viral load was 4.7 Log10. Second-line regimens prescribed were ddI/3TC/LPV/r (65.7%), ddI/TDF/LPV/r (10.0%), ddI/AZT/LPV/r (8.6%) and TDF/3TC/LPV/r (7.1%). The median CD4 T cell gain was +258 cells/mm³ at 24 months (n = 63). After 24 months of follow up, 92.3% (60/65) of the patients presented undetectable viral loads, giving an overall treatment success rate of 85.7% (CI: 75.6- 92.0) in intent-to-treat analysis. CONCLUSIONS: These data suggest that a LPV/r-based second-line regimen is associated with a high rate of virological suppression and immune reconstitution after 24 months of follow up in Cambodia.

Immunovirological outcomes and resistance patterns at 4 years of antiretroviral therapy use in HIV-infected patients in Cambodia.

OBJECTIVES: To report immunovirological outcomes and resistance patterns in adults treated with triple combination antiretroviral therapy (cART) for 4 years in an HIV programme of Phnom Penh, Cambodia. METHODS: It is a longitudinal study and cross-sectional evaluation of adults receiving cART for 4 years. CD4 cell counts and HIV-1 RNA were quantified, and resistance patterns were determined. Drug-related toxicity was assessed by clinicians and through laboratory testing. RESULTS: After 4 years of cART start, the cumulative probability of retention in care was 0.80 and survival among patients not lost to follow-up was 0.85. A total of 349 patients (98% of eligible) participated in the cross-sectional evaluation. Ninety per cent were receiving first-line therapy, 29% stavudine- and 58% zidovudine-containing regimens (compared with 94% and 3% at cART initiation). Ninety-three per cent of patients were clinically asymptomatic, and severe lipodystrophy and dyslipidemia were diagnosed in 7.2% and 4.0%, respectively. Good treatment adherence was reported by 83% of patients. Median CD4 T-cell count was 410 cells/µl [IQR 290-511], and 90% of patients had >200 cells/µl. Only 15 (4%) patients had detectable HIV viral load (eight had <200 CD4 cells/µl), five had thymidine analogue mutations, and nine were resistant to two drug classes. In an intention-to-treat analysis, 26.1% (95% CI 22.0-30.5) of patients had failed first-line therapy. CONCLUSIONS: In this Cambodian cohort of adults who started cART at an advanced stage of HIV disease, we observed good clinical and immunovirological outcomes and self-reported treatment adherence at 4 years of therapy.

Prediction of HIV type 1 subtype C tropism by genotypic algorithms built from subtype B viruses.

BACKGROUND: Genotypic predictions of HIV-1 tropism could simplify CCR5 antagonist usage. However, the genotypic algorithms built from subtype B viruses could be inadequate for non-B subtypes. We therefore performed paired genotypic and phenotypic determination of subtype C tropism. METHODS: We studied 52 patients recruited in Malawi and 21 patients recruited in France. We directly sequenced the V3 env region and performed a recombinant virus phenotypic entry assay in parallel. RESULTS: The Malawi patients had 29% of CXCR4-using subtype C viruses compared with only 5% in the patients from France. For detecting CXCR4-using subtype C viruses, the genotypic rule combining the amino acids at positions 11/25 and the net charge of V3 was 93.3% sensitive and 96.4% specific. The Geno2pheno tool was 86.7% sensitive and 89.1% specific. The WebPSSM tool with the SI/NSI matrix was 80% sensitive and 98.2% specific in its subtype B version and 93.3% sensitive and 81.8% specific in its subtype C version. CONCLUSIONS: The genotypic determinants of coreceptor usage for HIV-1 subtype C were mainly in V3 and were globally similar to those previously reported for subtype B viruses. The main genotypic algorithms built from subtype B viruses perform well when applied to subtype C viruses.

Prevalence study of yaws in the Democratic Republic of Congo using the lot quality assurance sampling method.

BACKGROUND: Until the 1970s the prevalence of non-venereal trepanomatosis, including yaws, was greatly reduced after worldwide mass treatment. In 2005, cases were again reported in the Democratic Republic of the Congo. We carried out a survey to estimate the village-level prevalence of yaws in the region of Equator in the north of the country in order to define appropriate strategies to effectively treat the affected population. METHODOLOGY/PRINCIPAL FINDINGS: We designed a community-based survey using the Lot Quality Assurance Sampling method to classify the prevalence of active yaws in 14 groups of villages (lots). The classification into high, moderate, or low yaws prevalence corresponded to World Health Organization prevalence thresholds for identifying appropriate operational treatment strategies. Active yaws cases were defined by suggestive clinical signs and positive rapid plasma reagin and Treponema pallidum hemagglutination serological tests. The overall prevalence in the study area was 4.7% (95% confidence interval: 3.4-6.0). Two of 14 lots had high prevalence (>10%), three moderate prevalence (5-10%) and nine low prevalence (<5%.). CONCLUSIONS/SIGNIFICANCE: Although yaws is no longer a World Health Organization priority disease, the presence of yaws in a region where it was supposed to be eradicated demonstrates the importance of continued surveillance and control efforts. Yaws should remain a public health priority in countries where previously it was known to be endemic. The integration of sensitive surveillance systems together with free access to effective treatment is recommended. As a consequence of our study results, more than 16,000 people received free treatment against yaws.

Prevalence, risk factors, and impact on outcome of cytomegalovirus replication in serum of Cambodian HIV-infected patients (2004-2007).

BACKGROUND: In developing countries, the study of cytomegalovirus (CMV) coinfection in HIV-infected patients remains neglected. Quantitative CMV polymerase chain reaction (PCR) is the gold standard diagnostic tool for analyzing serum CMV replication and for predicting CMV disease. We estimated the prevalence of replicating CMV in sera of newly diagnosed HIV-infected Cambodian patients and examined its impact on mortality. METHODS: This cohort study was based on 2 highly active antiretroviral therapy treatment programs in Cambodia between 2004 and 2007. Quantitative CMV PCR was performed on baseline serum samples of 377 HIV-infected patients. RESULTS: The prevalence of serum CMV DNA was 55.2% (150 of 272) in patients with CD4 count <100/mm. In multivariate analysis, hemoglobin <9 g/dL, CD4 count <100/mm, and Karnofsky index <50 were independently associated with positive serum CMV DNA at baseline. During a 3-year follow-up period, CMV viral load >or=3.1 log10 copies per milliliter was significantly associated with death independently of CD4 count, other opportunistic infections, and highly active antiretroviral therapy. CONCLUSIONS: As in industrialized countries, serum CMV replication is highly prevalent among HIV-infected Cambodian patients and is associated with increased mortality. This underscores the importance of diagnostic CMV infection by PCR in sera of HIV-infected patients with CD4 count <100/mm and treating this opportunistic infection to reduce its associated mortality.

Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries.

BACKGROUND: In developing countries, access to laboratory tests remains limited, and the use of simple tools such as weight to monitor HIV-infected patients treated with antiretroviral therapy should be evaluated. METHODS: Cohort study of 2451 Cambodian and 2618 Kenyan adults who initiated antiretroviral therapy between 2001 and 2007. The prognostic value of weight gain at 3 months of antiretroviral therapy on 3-6 months mortality, and at 6 months on 6-12 months mortality, was investigated using Poisson regression. RESULTS: Mortality rates [95% confidence interval (CI)] between 3 and 6 months of antiretroviral therapy were 9.9 (7.6-12.7) and 13.5 (11.0-16.7) per 100 person-years in Cambodia and Kenya, respectively. At 3 months, among patients with initial body mass index less than or equal to 18.5 kg/m (43% of the study population), mortality rate ratios (95% CI) were 6.3 (3.0-13.1) and 3.4 (1.4-8.3) for those with weight gain less than or equal to 5 and 5-10%, respectively, compared with those with weight gain of more than 10%. At 6 months, weight gain was also predictive of subsequent mortality: mortality rate ratio (95% CI) was 7.3 (4.0-13.3) for those with weight gain less than or equal to 5% compared with those with weight gain of more than 10%. CONCLUSION: Weight gain at 3 months is strongly associated with survival. Poor compliance or undiagnosed opportunistic infections should be investigated in patients with initial body mass index less than or equal to 18.5 and achieving weight gain less than or equal to 10%.