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Background In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. Methods We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. Results A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment. Conclusions Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events. (Funded by the Agence Nationale de Recherches sur le Sida et les Hepatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number, NCT02057796.).

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.

INTRODUCTION: In Cambodia the Linked Response (LR) approach for strengthening linkages between HIV and reproductive health services especially for the prevention of mother-to-child transmission of HIV (PMTCT) was scaled up in 2009. This article describes the LR scale-up and the concomitant evolution of key PMTCT indicators at the national level. METHODS: A descriptive analysis of routine LR PMTCT programme data and national laboratory data from 2008 to 2012 was conducted. RESULTS: LR data show that between 2008 and 2012 the number of LR/PMTCT sites increased from 67 to 956 (of 1004) public health facilities to cover 74 (of 77) operational districts. In LR operational districts the number of pregnant women (PW) tested for HIV increased from 41800 in 2009 to 269935 [of whom 375 (0.14%) were newly tested positive for HIV] in 2012; the number of PW living with HIV and exposed infants receiving antiretrovirals increased from 49 and 44 in 2009 to 720 and 551 in 2012 respectively. Concomitantly national PMTCT programme data showed that the percent of PW tested for HIV increased from 34.4% (117832 of 342929 estimated PW) in 2008 to 86.1% (324996 of 377340) in 2012. In 2012 65.3% (862 of 1321) of estimated HIV-positive PW and 72.7% (960 of 1321) of exposed infants received antiretrovirals. By 6-8 weeks postpartum 7.4% (8 of 108) and 1.5% (6 of 409) of DNA-polymerase chain reaction tested positive in 2008 and in 2012 respectively. CONCLUSIONS: The LR approach provided a model which catalyzed increased access of PW to HIV testing and treatment thereby contributing to the scale-up of PMTCT service provision and improved coverage in Cambodia.

OBJECTIVES To describe the implementation and results of the linked response (LR) in Cambodia after 18 months of follow-up. METHODS The main objectives of the LR are to increase access to sexually transmitted infection/HIV prevention, testing, care, and treatment and to strengthen existing reproductive health services through increased linkages within and between public health facilities and community-based services. The LR was piloted in Cambodia in 2008, in 2 demonstration projects, covering 5 operational districts. Routine data were collected and analyzed before (2007), during (2008), and after (2009) the implementation of the LR. RESULTS Overall in the 5 operational districts, the proportion of pregnant women, tested for HIV increased from 6% (1261 of 21,376) in 2007 to 86% (18394 of 21,478) in 2009. Syphilis testing, introduced early 2009, reached similar (85%) coverage as HIV by the end of 2009. Between 2007 and 2009, reproductive indicators also increased: antenatal care coverage (at least 1 visit) from 80% to 100%, public health facility delivery rates from 26% to 46%, and contraceptive prevalence from 24% to 28%. Antiretroviral uptake was high among HIV-positive mothers and exposed infants, 84% and 95% respectively, and 3 of 36 (8%) infants tested so far for HIV were diagnosed positive. However, 6 maternal (HIV-positive women) and 7 child deaths (1 tested positive) occurred during the pregnancy or the 30-week postpartum follow-up period. CONCLUSIONS Sexually transmitted infection/HIV indicators and follow-up dramatically improved after the LR was implemented. Efforts should be pursued to further improve quality of health care services.