BACKGROUND: Tuberculosis (TB) preventive treatment (TPT) is recommended by the World Health Organization (WHO) for persons living with HIV, including pregnant and breastfeeding women. Given the President's Emergency Plan for AIDS Relief (PEPFAR)'s investment in TPT services for persons living with HIV as a strategy to prevent TB as well as uncertainty in guidelines and policy regarding use of TPT during pregnancy and the postpartum period, we conducted a review of current relevant national guidelines among PEPFAR-supported countries. METHODS: Our review included 44/49 PEPFAR-supported countries to determine if TB screening and TPT are recommended specifically for pregnant and breastfeeding women living with HIV (WLHIV). National guidelines reviewed and abstracted included TB, HIV, prevention of vertical HIV transmission, TPT, and any other relevant guidelines. We abstracted information regarding TB screening, including screening tools and frequency; and TPT, including timing, regimen, frequency, and laboratory monitoring. RESULTS: Of 44 PEPFAR-supported countries for which guidelines were reviewed, 66% were high TB incidence countries; 41% were classified by WHO as high TB burden countries, and 43% as high HIV-associated TB burden countries. We found that 64% (n = 28) of countries included TB screening recommendations for pregnant WLHIV in their national guidelines, and most (n = 35, 80%) countries recommend TPT for pregnant WLHIV. Fewer countries included recommendations for breastfeeding as compared to pregnant WLHIV, with only 32% (n = 14) mentioning TB screening and 45% (n = 20) specifically recommending TPT for this population; most of these recommend isoniazid-based TPT regimens for pregnant and breastfeeding WLHIV. However, several countries also recommend isoniazid combined with rifampicin (3RH) or rifapentine (3HP). CONCLUSIONS: Despite progress in the number of PEPFAR-supported countries that specifically include TB screening and TPT recommendations for pregnant and breastfeeding WLHIV in their national guidelines, many PEPFAR-supported countries still do not include specific screening and TPT recommendations for pregnant and breastfeeding WLHIV.

INTRODUCTION: The COVID-19 pandemic has impacted global health service delivery, including provision of HIV services. Countries with high HIV burden are balancing the need to minimize interactions with health facilities to reduce the risk of COVID-19 transmission, while delivering uninterrupted essential HIV prevention, testing and treatment services. Many of these adaptations in resource-constrained settings have not adequately accounted for the needs of pregnant and breastfeeding women, infants, children and adolescents. We propose whole-family, tailored programme adaptations along the HIV clinical continuum to protect the programmatic gains made in services. DISCUSSION: Essential HIV case-finding services for pregnant and breastfeeding women and children should be maintained and include maternal testing, diagnostic testing for infants exposed to HIV, index testing for children whose biological parents or siblings are living with HIV, as well as for children/adolescents presenting with symptoms concerning for HIV and comorbidities. HIV self-testing for children two years of age and older should be supported with caregiver and provider education. Adaptations include bundling services in the same visit and providing testing outside of facilities to the extent possible to reduce exposure risk to COVID-19. Virtual platforms can be used to identify vulnerable children at risk of HIV infection, abuse, harm or violence, and link them to necessary clinical and psychosocial support services. HIV treatment service adaptations for families should focus on family based differentiated service delivery models, including community-based ART initiation and multi-month ART dispensing. Viral load monitoring should not be a barrier to transitioning children and adolescents experiencing treatment failure to more effective ART regimens, and viral load monitoring for pregnant and breastfeeding women and children should be prioritized and bundled with other essential services. CONCLUSIONS: Protecting pregnant and breastfeeding women, infants, children and adolescents from acquiring SARS-CoV-2 while sustaining essential HIV services is an immense global health challenge. Tailored, family friendly programme adaptations for case-finding, ART delivery and viral load monitoring for these populations have the potential to limit SARS-CoV-2 transmission while ensuring the continuity of life-saving HIV case identification and treatment efforts.

BACKGROUND: The Xpert((R)) MTB/RIF (Xpert) test has been shown to be effective and cost-effective for diagnosing tuberculosis (TB) under conditions with high HIV prevalence and HIV-TB co-infection but less is known about Xpert's cost in low HIV prevalence settings. Cambodia, a country with low HIV prevalence (0.7%), high TB burden, and low multidrug-resistant (MDR) TB burden (1.4% of new TB cases, 11% of retreatment cases) introduced Xpert into its TB diagnostic algorithms for people living with HIV (PLHIV) and people with presumptive MDR TB in 2012. The study objective was to estimate these algorithms' costs pre- and post-Xpert introduction in four provinces of Cambodia. METHODS: Using a retrospective, ingredients-based microcosting approach, primary cost data on personnel, equipment, maintenance, supplies, and specimen transport were collected at four sites through observation, records review, and key informant consultations. RESULTS: Across the sample facilities, the cost per Xpert test was US$33.88-US$37.11, clinical exam cost US$1.22-US$1.84, chest X-ray cost US$2.02-US$2.14, fluorescent microscopy (FM) smear cost US$1.56-US$1.93, Ziehl-Neelsen (ZN) smear cost US$1.26, liquid culture test cost US$11.63-US$22.83, follow-on work-up for positive culture results and Mycobacterium tuberculosis complex (MTB) identification cost US$11.50-US$14.72, and drug susceptibility testing (DST) cost US$44.26. Specimen transport added US$1.39-US$5.21 per sample. Assuming clinician adherence to the algorithms and perfect test accuracy, the normative cost per patient correctly diagnosed under the post-Xpert algorithms would be US$25-US$29 more per PLHIV and US$34-US$37 more per person with presumptive MDR TB (US$41 more per PLHIV when accounting for variable test sensitivity and specificity). CONCLUSIONS: Xpert test unit costs could be reduced through lower cartridge prices, longer usable life of GeneXpert((R)) (Cepheid, USA) instruments, and increased test volumes; however, epidemiological and test eligibility conditions in Cambodia limit the number of specimens received at laboratories, leading to sub-optimal utilization of current instruments. Improvements to patient referral and specimen transport could increase test volumes and reduce Xpert test unit costs in this setting.

Background: In 2014-2015, 242 individuals aged 2-89 were newly HIV-1 diagnosed 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 and B viruses (HCV, HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV, and HBcIgM Ab for HBV. We performed evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed health care practitioner were obtained from 193 cases and 1499 controls during interviews. Results: Cases were co-infected 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=0.04). Fifty-nine (38.6%) of 153 tested cases showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed three main clades, one containing 34 subtypes 1b with tMRCA in 2012, and two 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.

SETTING: National Tuberculosis (TB) Program sites in northwest Cambodia. OBJECTIVE: To evaluate the impact of Xpert((R)) MTB/RIF at point of care (POC) as compared to non-POC sites on the diagnostic evaluation of people living with the human immunodeficiency virus (PLHIV) with TB symptoms and patients with possible multidrug-resistant (MDR) TB. DESIGN: Observational cohort of patients undergoing routine diagnostic evaluation for TB following the rollout of Xpert. RESULTS: Between October 2011 and June 2013, 431 of 822 (52%) PLHIV with TB symptoms and 240/493 (49%) patients with possible MDR-TB underwent Xpert. Xpert was more likely to be performed when available as POC. A smaller proportion of PLHIV at POC sites were diagnosed with TB than at non-POC sites; however, at POC sites, a higher proportion of those diagnosed with TB were bacteriologically positive. There was poor agreement between Xpert and other tests such as smear microscopy and culture. Overall, the evaluation of patients with possible MDR-TB increased following Xpert rollout, yet for patients confirmed as having drug resistance on drug susceptibility testing, only 46% had rifampin resistance that would be identified with Xpert. CONCLUSION: Although utilization of Xpert was low, it may have contributed to an increase in evaluations for possible MDR-TB and a decline in empiric treatment for PLHIV when available as POC.

In December 2014, local health authorities in Battambang province in northwest Cambodia reported 30 cases of human immunodeficiency virus (HIV) infection in a rural commune (district subdivision) where only four cases had been reported during the preceding year. The majority of cases occurred in residents of Roka commune. The Cambodian National Center for HIV/AIDS (acquired immunodeficiency syndrome), Dermatology and Sexually Transmitted Diseases (NCHADS) investigated the outbreak in collaboration with the University of Health Sciences in Phnom Penh and members of the Roka Cluster Investigation Team. By February 28, 2015, NCHADS had confirmed 242 cases of HIV infection among the 8,893 commune residents, an infection rate of 2.7%. Molecular investigation of the HIV strains present in this outbreak indicated that the majority of cases were linked to a single HIV strain that spread quickly within this community. An NCHADS case-control study identified medical injections and infusions as the most likely modes of transmission. In response to this outbreak, the Government of Cambodia has taken measures to encourage safe injection practices by licensed medical professionals, ban unlicensed medical practitioners, increase local capacity for HIV testing and counseling, and expand access to HIV treatment in Battambang province. Measures to reduce the demand for unnecessary medical injections and the provision of unsafe injections are needed. Estimates of national HIV incidence and prevalence might need to be adjusted to account for unsafe injection as a risk exposure.

OBJECTIVE: To describe the implementation and utilization of the Xpert MTB/RIF (Xpert) assay to diagnose tuberculosis (TB) among people living with the human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS, PLHA) in Cambodia. DESIGN: Following the rollout of Xpert, an evaluation was conducted in four provinces of Cambodia from March to December 2012 to determine the utilization, performance, and turnaround time (TAT) of Xpert among PLHA. Data were collected from paper-based patient registers. RESULTS: Of 497 PLHA with a positive TB symptom screen, 357 (72%) were tested with smear microscopy, and 250 (50%) with Xpert; 25 (10%) PLHA tested with Xpert were positive for TB and none were rifampicin-resistant. The utilization of Xpert increased from 23% to 75%, with a median TAT of 1 day. Across districts, utilization ranged from zero to 85%, while the TAT ranged from zero to 22 days. CONCLUSION: While early data show increasing utilization of Xpert for PLHA with a positive symptom screen, most patients underwent smear microscopy as an initial diagnostic test. Training delays and challenges associated with specimen referral may have contributed to variability in Xpert uptake and TAT, particularly for sites without onsite Xpert testing. Enhanced programmatic support, particularly for specimen referral and results reporting, may facilitate appropriate utilization.

Worldwide elimination of HIV transmission from mother-to-child is theoretically achievable. In Cambodia, antenatal care (ANC) prevalence has dropped from 1.6% (2003) to 0.71% (2009). However, success in minimizing vertical transmission has been limited by low testing uptake at ANC and delivery. We trained midwives in counselling and performance of an HIV rapid test, incorporated point-of-care testing into routine antenatal and maternity services and determined acceptability, feasibility, accuracy, cost and yield after one year. In all, 97.3% of ANC clients and 73.0% of maternity admissions had unknown HIV status. Testing was offered to 97.6% and 95.0% of untested ANC and maternity clients, respectively. Acceptance rates were 95.5% and 99.4%. Partner testing rate was 38.6%. HIV was diagnosed in 0.1% of ANC clients, 0.4% of partners and 0.9% of women at delivery. For an operational district with an average population of 158,000, point-of-care testing was estimated in one year to identify 19 HIV-infected pregnant women, nine men, 14 discordant couples and 16 exposed infants who otherwise would have not received prophylaxis. Cost was less than $3.75 per person tested. Point-of-care testing during ANC and at delivery is feasible, acceptable and contributes to reducing mother-to-child transmission.