Costs and Cost-Effectiveness of mCME Version 2.0: An SMS-Based Continuing Medical Education Program for HIV Clinicians in Vietnam.

BACKGROUND: The Mobile Continuing Medical Education (mCME) 2.0 project was a randomized controlled trial that found that a 6-month text message-based CME intervention improved both the use of online medical training resources and medical knowledge among a cadre of HIV clinicians in Vietnam. This companion study analyzed intervention costs and cost-effectiveness. METHODS: We conducted (1) a financial analysis based on costs incurred during the trial's planning and implementation; (2) an economic analysis to consider resource utilization; and (3) cost-effectiveness analyses to estimate cost inputs relative to impact: increase in self-study (measured by visits to online courses) and increase in knowledge (measured by exam score improvement) (in 2016 US$). Finally, we estimated the economic cost of a 9-month national program and a 10-year scaled-up model (in 2021 US$). RESULTS: The total financial cost of the intervention was US$49,552; the main cost drivers were personnel time (71.4%) and technology inputs (14.9%). The total economic cost was estimated at US$92,212, with the same key cost inputs (representing 77.7% and 8.0%, respectively, of total costs). The financial cost per 10% increase in accessing online courses was US$923, while the cost of improving knowledge, measured by a 10% improvement in mean exam score across the study population, was US$32,057 (US$605 per intervention clinician). The comparable total economic cost of each improvement, respectively, was US$1,770 and US$61,452 (US$1,159 per intervention clinician). A future 9-month national program was estimated to cost US$37,403, while the full 10-year scaled-up program was estimated at US$196,446. CONCLUSIONS: This analysis indicates that leveraging mobile technology could be a feasible way to provide distance learning to health professions across Vietnam at a relatively low cost. Given the need for practical ways to expand CME in resource-constrained regions of the world, this approach warrants further study and possible adoption.

Real-time Feedback to Improve HIV Treatment Adherence in Pregnant and Postpartum Women in Uganda: A Randomized Controlled Trial.

We assessed an intervention aimed at improving adherence to antiretroviral therapy (ART) among pregnant and postpartum women living with HIV (PPWLH). We randomized 133 pregnant women initiating ART in Uganda to receive text reminders generated by real time-enabled electronic monitors and data-informed counseling through 3 months postpartum (PPM3) or standard care. Intention-to-treat analyses found low adherence levels and no intervention impact. Proportions achieving ≥95% adherence in PPM3 were 16.4% vs. 9.1% (t = -1.14, p = 0.26) in intervention vs. comparison groups, respectively; 30.9% vs. 29.1% achieved ≥80% adherence. Additional analyses found significant adherence declines after delivery, and no effect on disease progression (CD4-cell count, viral load), though treatment interruptions were significantly fewer in intervention participants. Per-protocol analyses encompassing participants who used adherence monitors as designed experienced better outcomes, suggesting potential benefit for some PPWLH. The study was registered on ClinicalTrials.Gov (NCT02396394).

If we build it, will they come? Results of a quasi-experimental study assessing the impact of maternity waiting homes on facility-based childbirth and maternity care in Zambia.

INTRODUCTION: Maternity waiting homes (MWHs) aim to increase access to maternity and emergency obstetric care by allowing women to stay near a health centre before delivery. An improved MWH model was developed with community input and included infrastructure, policies and linkages to health centres. We hypothesised this MWH model would increase health facility delivery among remote-living women in Zambia. METHODS: We conducted a quasi-experimental study at 40 rural health centres (RHC) that offer basic emergency obstetric care and had no recent stockouts of oxytocin or magnesium sulfate, located within 2 hours of a referral hospital. Intervention clusters (n=20) received an improved MWH model. Control clusters (n=20) implemented standard of care. Clusters were assigned to study arm using a matched-pair randomisation procedure (n=20) or non-randomly with matching criteria (n=20). We interviewed repeated cross-sectional random samples of women in villages 10+ kilometres from their RHC. The primary outcome was facility delivery; secondary outcomes included postnatal care utilisation, counselling, services received and expenditures. Intention-to-treat analysis was conducted. Generalised estimating equations were used to estimate ORs. RESULTS: We interviewed 2381 women at baseline (March 2016) and 2330 at endline (October 2018). The improved MWH model was associated with increased odds of facility delivery (OR 1.60 (95% CI: 1.13 to 2.27); p<0.001) and MWH utilisation (OR 2.44 (1.62 to 3.67); p<0.001). The intervention was also associated with increased odds of postnatal attendance (OR 1.55 (1.10 to 2.19); p<0.001); counselling for family planning (OR 1.48 (1.15 to 1.91); p=0.002), breast feeding (OR 1.51 (1.20 to 1.90); p<0.001), and kangaroo care (OR 1.44 (1.15, 1.79); p=0.001); and caesarean section (OR 1.71 (1.16 to 2.54); p=0.007). No differences were observed in household expenditures for delivery. CONCLUSION: MWHs near well-equipped RHCs increased access to facility delivery, encouraged use of facilities with emergency care capacity, and improved exposure to counselling. MWHs can be useful in the effort to increase delivery at advanced facilities in areas where substantial numbers of women live remotely. TRIAL REGISTRATION NUMBER: NCT02620436.

Impact of a Maternal Prevention of Mother-to-child Transmission of HIV (PMTCT) Intervention on HIV-exposed Infants in Uganda.

BACKGROUND: Uganda has successfully reduced pediatric HIV infections through prevention of mother-to-child transmission of HIV (PMTCT) programs, yet little is known about adherence to infant-specific components of interventions. We hypothesized that infants born to mothers receiving the WiseMama (WM) electronic drug monitoring (EDM)-based adherence intervention would have increased uptake of six-week post-natal nevirapine (NVP) infant prophylaxis and better adherence to six-week early infant diagnosis (EID) HIV testing. METHODS: At two sites in Uganda, the Wise Infant Study (WIN) prospectively followed an infant cohort. Infants were born to women enrolled in an RCT testing the effect of real-time reminders delivered via EDM on maternal adherence to antiretroviral therapy. We assessed intrapartum and discharge receipt of NVP prophylaxis using pharmacy and infant HIV DNA testing laboratory data. RESULTS: Of 121 women eligible for WIN, 97 (80%) consented and enrolled; 46 had been randomized to control and 51 to intervention. There were no differences in receipt of a six-week NVP supply (control 87%, intervention 82%, p = 0.53). Receipt of any NVP prophylaxis did not vary by delivery location (p = 0.35), and although 12% of infants were delivered at non-study health facilities, they were not less likely to receive NVP at discharge (p = 0.37). Among infants with a completed HIV test, there was no difference in mean time to first test (control 52 days (SD 18), intervention 51 days (SD 15), p = 0.86). Only one infant, in the control group, tested positive for HIV. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: We found no significant differences in adherence to infant PMTCT practices between intervention and control infants with relatively high rates of NVP receipt albeit with suboptimal adherence to six-week EID testing. Further work is needed to ensure improved access, uptake, and follow-up of HIV-exposed infants in the Option B+ era.

Retention in HIV Care Among HIV-Seropositive Pregnant and Postpartum Women in Uganda: Results of a Randomized Controlled Trial.

We tested an intervention that aimed to increase retention in antiretroviral therapy (ART) among HIV-positive pregnant and postpartum women, a population shown to be vulnerable to poor ART outcomes. 133 pregnant women initiating ART at 2 hospitals in Uganda used real time-enabled wireless pill monitors (WPM) for 1 month, and were then randomized to receive text message reminders (triggered by late dose-taking) and data-informed counseling through 3 months postpartum or standard care. We assessed "full retention" (proportion attending all monthly clinic visits and delivering at a study facility; "visit retention" (proportion of clinic visits attended); and "postpartum retention" (proportion retained at 3 months postpartum). Intention-to-treat and per protocol analyses found that retention was relatively low and similar between groups, with no significant differences. Retention declined significantly post-delivery. The intervention was unsuccessful in this population, which experiences suboptimal ART retention and is in urgent need of effective interventions.

Quality and utilization patterns of maternity waiting homes at referral facilities in rural Zambia: A mixed-methods multiple case analysis of intervention and standard of care sites.

INTRODUCTION: Maternity waiting homes, defined as residential lodging near a health facility, are recommended by the WHO. An improved MWH model, responsive to community standards for functionality and comfort, was implemented at two purposively selected health facilities in rural Zambia providing comprehensive emergency obstetric and neonatal care (CEmONC) services (intervention MWHs), and compared to three existing standard-of-care MWHs (comparison MWHs) at other CEmONC sites in the same districts. METHODS: We used a mixed-methods time-series design for this analysis. Quantitative data including MWH quality, MWH utilization, and demographics of women utilizing MWHs were collected from September 2016 through May 2018 to capture pre-post intervention trends. Qualitative data were obtained from two focus group discussions conducted with pregnant women at intervention MWHs in August 2017 and May 2018. The primary outcomes were quality scoring of the MWHs and maternal utilization of the MWHs. RESULTS: MWH quality was similar at all sites during the pre-intervention time period, with a significant change in overall quality scores between intervention (mean score 83.8, SD 12) and comparison (mean score 43.1, SD 10.2) sites after the intervention (p <0.0001). Women utilizing intervention and comparison MWHs at all time points had very similar demographics. After implementation of the intervention, there were marked increases in MWH utilization at both intervention and comparison sites, with a greater percentage increase at one of two intervention sites. CONCLUSIONS: An improved MWH model can result in measurably improved quality scores for MWHs, and can result in increased utilization of MWHs at rural CEmONC facilities. MWHs are part of the infrastructure that might be needed for health systems to provide high quality "right place" maternal care in rural settings.

A Meta-analysis Assessing Diarrhea and Pneumonia in HIV-Exposed Uninfected Compared With HIV-Unexposed Uninfected Infants and Children.

OBJECTIVE: Previous studies have demonstrated that HIV-exposed uninfected (HEU) infants and children experience morbidity and mortality at rates exceeding those of their HIV-unexposed uninfected (HUU) counterparts. We sought to summarize the association between HEU vs. HUU infants and children for the outcomes of diarrhea and pneumonia. DESIGN: Meta-analysis. METHODS: We reviewed studies comparing infants and children in the 2 groups for these infectious disease outcomes, in any setting, from 1993 to 2018 from 6 databases. RESULTS: We included 12 studies, and 17,955 subjects total [n = 5074 (28.3%) HEU and n = 12,881 (71.7%) HUU]. Random-effects models showed HEU infants and children had a 20% increase in the relative risk of acute diarrhea and a 30% increase in the relative risk of pneumonia when compared with their HUU counterparts. When stratifying by time since birth, we showed that HEU vs. HUU children had a 50% and 70% increased risk of diarrhea and pneumonia, respectively, in the first 6 months of life. CONCLUSIONS: We show an increased risk of diarrhea and pneumonia for HEU vs. HUU infants and children. Although we acknowledge, and commend, the immense public health success of prevention of mother-to-child transmission, we now have an enlarging population of children that seem to be vulnerable to not only death, but increased morbidity. We need to turn our attention to understanding the underlying mechanism and designing effective public health solutions. Further longitudinal research is needed to elucidate possible underlying immunological and/or sociological mechanisms that explain these differences in morbidity.

Maternity waiting homes as part of a comprehensive approach to maternal and newborn care: a cross-sectional survey.

BACKGROUND: Increased encounters with the healthcare system at multiple levels have the potential to improve maternal and newborn outcomes. The literature is replete with evidence on the impact of antenatal care and postnatal care to improve outcomes. Additionally, maternity waiting homes (MWHs) have been identified as a critical link in the continuum of care for maternal and newborn health yet there is scant data on the associations among MWH use and antenatal/postnatal attendance, family planning and immunization rates of newborns. METHODS: A cross-sectional household survey was conducted to collect data from women who delivered a child in the past 13 months from catchment areas associated with 40 healthcare facilities in seven rural Saving Mothers Giving Life districts in Zambia. Multi-stage random sampling procedures were employed with a final sample of n = 2381. Logistic regression models with adjusted odds ratios and 95% confidence intervals were used to analyze the data. RESULTS: The use of a MWH was associated with increased odds of attending four or more antenatal care visits (OR = 1.45, 95% CI = 1.26, 1.68), attending all postnatal care check-ups (OR = 2.00, 95% CI = 1.29, 3.12) and taking measures to avoid pregnancy (OR = 1.31, 95% CI = 1.10, 1.55) when compared to participants who did not use a MWH. CONCLUSIONS: This is the first study to quantitatively examine the relationship between the use of MWHs and antenatal and postnatal uptake. Developing a comprehensive package of services for maternal and newborn care has the potential to improve acceptability, accessibility, and availability of healthcare services for maternal and newborn health. Maternity waiting homes have the potential to be used as part of a multi-pronged approach to improve maternal and newborn outcomes. TRIAL REGISTRATION: National Institutes of Health Trial Registration NCT02620436, Impact Evaluation of Maternity Homes Access in Zambia, Date of Registration - December 3, 2015.

Implementing the mobile continuing medical education (mCME) project in Vietnam: making it work and sharing lessons learned.

BACKGROUND: Mobile technology is a novel approach for delivering continuing medical education (CME), with numerous advantages including lower costs and the ability to reach larger numbers than traditional in-person CME workshops. METHODS: From May 2015 to May 2017, we conducted two randomized controlled trials in a phased approach to evaluate the effectiveness of a mobile CME (mCME) approach for two cadres of health professionals in Vietnam. The first randomized controlled trial (RCT) tested the use of an SMS-based educational intervention among Community-Based Physician's Assistants; while feasible and acceptable, this intervention failed to improve medical knowledge among participants. Given the failure of the first RCT, and drawing on qualitative work conducted with participants at the conclusion of the trial, various modifications were employed in the second RCT conducted among HIV specialist physicians in Vietnam. Version 2.0 of the mCME intervention did lead to significant improvement in medical knowledge among intervention participants. Here, we discuss in detail the development of an mCME platform and the experiential "lessons learned" during two phases of implementation. RESULTS: Numerous lessons were learned during implementation, including the importance of: (I) mixed methods approaches; (II) an underlying theoretical framework for behavior change projects; (III) expertise in software programming; (IV) aligning educational content to a well-defined participant population; and (V) engaging and motivating adult learners. We also discuss the critical importance of projects with local ownership and investment that are relevant to local problems. CONCLUSIONS: mHealth approaches for continued healthcare training and education is increasingly relevant in many low-resource settings, the lessons learned here will be valuable to other organizations looking to scale-up similar mHealth-type educational programmes.

Motivating HIV Providers in Vietnam to Learn: A Mixed-Methods Analysis of a Mobile Health Continuing Medical Education Intervention.

BACKGROUND: The Mobile Continuing Medical Education Project (mCME V.2.0) was a randomized controlled trial designed to test the efficacy of a text messaging (short message service [SMS])-based distance learning program in Vietnam that included daily quiz questions, links to readings and online courses, and performance feedback. The trial resulted in significant increases in self-study behaviors and higher examination scores for intervention versus control participants. OBJECTIVE: The objective of this mixed-methods study was to conduct qualitative and quantitative investigations to understand participants' views of the intervention. We also developed an explanatory framework for future trial replication. METHODS: At the endline examination, all intervention participants completed a survey on their perspectives of mCME and self-study behaviors. We convened focus group discussions to assess their experiences with the intervention and attitudes toward continuing medical education. RESULTS: A total of 48 HIV specialists in the intervention group completed the endline survey, and 30 participated in the focus group discussions. Survey and focus group data suggested that most clinicians liked the daily quizzes, citing them as convenient mechanisms to convey information in a relevant manner. A total of 43 of the 48 (90%) participants reported that the daily quizzes provided motivation to study for continuing medical education purposes. Additionally, 83% (40/48) of intervention participants expressed that they were better prepared to care for patients with HIV in their communities, compared with 67% (32/48) at baseline. Participation in the online coursework component was low (only 32/48, 67% of intervention participants ever accessed the courses), but most of those who did participate thought the lectures were engaging (26/32, 81%) and relevant (29/32, 91%). Focus group discussions revealed that various factors influenced the clinicians' decision to engage in higher learning, or "lateral learning," including the participant's availability to study, professional relevance of the topic area, and feedback. These variables serve as modifying factors that fit within an adapted version of the health belief model, which can explain behavior change in this context. CONCLUSIONS: Qualitative and quantitative endline data suggested that mCME V.2.0 was highly acceptable. Participant behaviors during the trial fit within the health belief model and can explain the intervention's impact on improving self-study behaviors. The mCME platform is an evidence-based approach with the potential for adoption at a national scale as a method for promoting continuing medical education. TRIAL REGISTRATION: ClinicalTrials.gov NCT02381743; https://clinicaltrials.gov/ct2/show/NCT02381743.

Maternity Waiting Home Use by HIV-positive Pregnant Women in Zambia: Opportunity for Improved Prevention of Maternal to Child Transmission of HIV.

BACKGROUND: Maternity waiting homes (MWHs), defined as residential lodging near health facilities, are an intervention to improve access to maternal care recommended by the World Health Organization. Little is known about utilization of MWHs by HIV-positive women. This paper describes: 1) maternal awareness and utilization of MWHs in rural Zambia among HIV-positive women, and 2) health outcomes for HIV-positive women and their infants with regards to utilization of MWHs. METHODS: Data were collected from recently delivered women (delivered after 35 weeks in the previous 12 months) living >9.5 km from 40 health facilities in rural Zambia. For our analysis, primary outcomes were compared between self-identified HIV-positive and HIV-negative women in the sample. Primary outcomes include: 1) awareness of MWHs and 2) utilization of MWHs. We summarized simple descriptive statistics, stratified by maternal self-reported HIV status. We conducted bivariate analyses using chi-square tests, t-tests and Wilcoxon rank sum test. RESULTS: Among 2,381 women, 50 (2.4%) self-identified as HIV-positive. HIV-positive women were older and had more pregnancies and children than HIV-negative women (p<0.001). There was no difference in awareness of MWHs, but HIV-positive women were more likely to use a MWH than HIV-negative women. There was no difference in receipt of infant antiretroviral prophylaxis between women who did or did not stay at a MWH. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Though HIV prevalence in this sample was lower than expected, MWHs may represent a useful strategy to improve prevention of mother to child transmission of HIV in high prevalence, low-resource settings.

The Supporting Adolescent Adherence in Vietnam (SAAV) study: study protocol for a randomized controlled trial assessing an mHealth approach to improving adherence for adolescents living with HIV in Vietnam.

BACKGROUND: The overall goal of the Supporting Adolescent Adherence in Vietnam (SAAV) study is to improve understanding of an adherence feedback mHealth intervention designed to help adolescents living with HIV (ALHIV) maintain high adherence to antiretroviral therapy (ART), critical to effective treatment. Specifically, we aim to: (1) conduct formative research with Vietnamese ALHIV and their caregivers to better understand adherence challenges and refine the personalized mHealth intervention package; and (2) assess the feasibility, acceptability, and efficacy of the intervention to improve ART adherence by implementing a randomized controlled trial (RCT). METHODS: The study will utilize mixed methods. The formative phase will include 40 in-depth interviews (IDIs) with 20 adolescent (12-17 years)/caregiver dyads and eight focus group discussions with adolescents, caregivers, and clinicians at the National Hospital for Pediatrics (NHP) in Hanoi, Vietnam. We will also conduct 20 IDIs with older adolescents (18-21 years) who have transitioned to adult care at outpatient clinics in Hanoi. We will then implement a seven-month RCT at NHP. We will recruit 80 adolescents on ART, monitor their adherence for one month to establish baseline adherence using a wireless pill container (WPC), and then randomize participants to intervention versus control within optimal (≥ 95% on-time doses) versus suboptimal (< 95% on-time doses) baseline adherence strata. Intervention participants will receive a reminder of their choice (cellphone text message/call or bottle-based flash/alarm), triggered when they miss a dose, and engage in monthly counseling informed by their adherence data. Comparison participants will receive usual care and offer of counseling at routine monthly clinic visits. After six months, we will compare ART adherence, CD4 count, and HIV viral suppression between arms, in addition to acceptability and feasibility of the intervention. DISCUSSION: Findings will contribute valuable information on perceived barriers and facilitators affecting adolescents' ART adherence, mHealth approaches as adherence support tools for ALHIV, and factors affecting adolescents' ART adherence. This information will be useful to researchers, medical personnel, and policy-makers as they develop and implement adherence programs for ALHIV, with potential relevance to other chronic diseases during transition from adolescent to adult care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03031197 . Registered on 21 January 2017.

Unpacking the "Black Box": How an SMS-Based Continuing Medical Education Intervention Improved Medical Knowledge Among HIV Clinicians in Vietnam.

BACKGROUND: A mobile-based continuing medical education (mCME) intervention implemented over 6 months between 2016 and 2017, consisting of daily SMS multiple choice quizzes and access to online daily readings and CME courses, was shown to be effective in increasing medical knowledge among HIV providers in Vietnam. We hypothesized this improvement was a result of "lateral learning," a process in which the daily SMS quizzes acted as a stimulus for interacting with other study materials. METHODS: We explored how study materials directly provided by the intervention-the daily readings and the online CME courses-and independent study behaviors, such as using medical textbooks and reviewing national guidelines, contributed to medical knowledge as measured by baseline and endline exams. At baseline, there were 53 participants each in the intervention and control groups (N=106). Using linear regression models, we estimated the association between intervention-prompted and independent study behaviors and endline test scores. We also conducted a series of interaction analyses to test the extent to which the effect of daily quiz performance on endline test scores depended on use of the intervention-prompted or independent study materials. Finally, we estimated the proportion of variance in endline test scores explained by each of the intervention-prompted behaviors. RESULTS: The average medical knowledge test score among all participants was 46% at baseline and 54% at endline. Among the intervention group, 82% of the daily quizzes were answered, although only about half were answered correctly. Responding to the daily quizzes (ß=0.24; P=.05), quiz performance (ß=0.42; P<.001), and accessing daily readings (ß=0.22; P=.06) were statistically significantly associated with higher endline test scores. While accessing the online CME courses and some of the independent study behaviors, such as use of medical textbooks, had positive associations with endline test scores, none reached statistical significance. Quiz performance explained 51% of the variation in endline test scores. Interaction analysis found that quiz performance had a stronger, but not statistically significant, association with endline test scores when both daily readings (ß=0.87; P=.08) and online CME courses (ß=0.25; P=.09) were accessed more frequently. CONCLUSION: In mCME interventions, daily SMS quizzes can effectively act as a stimulus for uptake of study behaviors when paired with access to relevant readings and online courses. While further investigation is needed to more fully understand the role of outside study materials, we believe this model has the potential for further use in Vietnam and other low-resource settings.

Impact of maternity waiting homes on facility delivery among remote households in Zambia: protocol for a quasiexperimental, mixed-methods study.

INTRODUCTION: Maternity waiting homes (MWHs) aim to improve access to facility delivery in rural areas. However, there is limited rigorous evidence of their effectiveness. Using formative research, we developed an MWH intervention model with three components: infrastructure, management and linkage to services. This protocol describes a study to measure the impact of the MWH model on facility delivery among women living farthest (≥10 km) from their designated health facility in rural Zambia. This study will generate key new evidence to inform decision-making for MWH policy in Zambia and globally. METHODS AND ANALYSIS: We are conducting a mixed-methods quasiexperimental impact evaluation of the MWH model using a controlled before-and-after design in 40 health facility clusters. Clusters were assigned to the intervention or control group using two methods: 20 clusters were randomly assigned using a matched-pair design; the other 20 were assigned without randomisation due to local political constraints. Overall, 20 study clusters receive the MWH model intervention while 20 control clusters continue to implement the 'standard of care' for waiting mothers. We recruit a repeated cross section of 2400 randomly sampled recently delivered women at baseline (2016) and endline (2018); all participants are administered a household survey and a 10% subsample also participates in an in-depth interview. We will calculate descriptive statistics and adjusted ORs; qualitative data will be analysed using content analysis. The primary outcome is the probability of delivery at a health facility; secondary outcomes include utilisation of MWHs and maternal and neonatal health outcomes. ETHICS AND DISSEMINATION: Ethical approvals were obtained from the Boston University Institutional Review Board (IRB), University of Michigan IRB (deidentified data only) and the ERES Converge IRB in Zambia. Written informed consent is obtained prior to data collection. Results will be disseminated to key stakeholders in Zambia, then through open-access journals, websites and international conferences. TRIAL REGISTRATION NUMBER: NCT02620436; Pre-results.

Regimen durability in HIV-infected children and adolescents initiating first-line antiretroviral therapy in a large public sector HIV cohort in South Africa.

INTRODUCTION: In April 2010, tenofovir and abacavir replaced stavudine in public sector first-line antiretroviral therapy (ART) for children under 20 years old in South Africa. The association of both abacavir and tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir or abacavir-based regimens. We evaluated changes over time in regimen durability for paediatric patients 3-19 years of age at eight public sector clinics in Johannesburg, South Africa. METHODS: Cohort analysis of treatment-naïve, non-pregnant paediatric patients from 3 to 19 years old initiated on ART between April 2004 and December 2013. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir and/or abacavir was substituted for stavudine after April 2010 in first-line ART. We evaluated the frequency and type of single-drug substitutions, treatment interruptions and switches to second-line therapy. Fine and Gray competing risk regression models were used to evaluate the association of antiretroviral drug type with single-drug substitutions, treatment interruptions and second-line switches in the first 24 months on treatment. RESULTS: Three hundred and ninety-eight (15.3%) single-drug substitutions, 187 (7.2%) treatment interruptions and 86 (3.3%) switches to second-line therapy occurred among 2602 paediatric patients over 24-months on ART. Overall, the rate of single-drug substitutions started to increase in 2009, peaked in 2011 at 25% and then declined to 10% in 2013, well after the integration of tenofovir into paediatric regimens; no patients over the age of 3 were initiated on abacavir for first-line therapy. Competing risk regression models showed patients on zidovudine or stavudine had upwards of a fivefold increase in single-drug substitution vs. patients initiated on tenofovir in the first 24 months on ART. Older adolescents also had a two- to threefold increase in treatment interruptions and switches to second-line therapy compared to younger patients in the first 24 months on ART. CONCLUSIONS: The decline in single-drug substitutions is associated with the introduction of tenofovir. Tenofovir use could improve regimen durability and treatment outcomes in resource-limited settings.

mCME project V.2.0: randomised controlled trial of a revised SMS-based continuing medical education intervention among HIV clinicians in Vietnam.

BACKGROUND: Continuing medical education (CME) is indispensable, but costs are a barrier. We tested the effectiveness of a novel mHealth intervention (mCME V.2.0) promoting CME among Vietnamese HIV clinicians. METHODS: We enrolled HIV clinicians from three provinces near Hanoi. The 6-month intervention consisted of (1) daily short message service multiple-choice quiz questions, (2) daily linked readings, (3) links to online CME courses and (4) feedback messages describing the performance of the participant relative to the group. Control participants had equal access to the online CME courses. Our primary endpoint was utilisation of the online CME courses; secondary endpoints were self-study behaviour, performance on a standardised medical exam and job satisfaction. RESULTS: From 121 total HIV clinicians in the three provinces, 106 (87.6%) enrolled, and 48/53 intervention (90%) and 47/53 control (89%) participants completed the endline evaluations. Compared with controls, intervention participants were more likely to use the CME courses (risk ratio (RR) 2.3, 95% CI 1.4 to 3.8, accounting for 83% of course use (P<0.001)). Intervention participants increased self-study behaviours over controls in terms of use of medical textbooks (P<0.01), consulting with colleagues (P<0.01), searching on the internet (P<0.001), using specialist websites (P=0.02), consulting the Vietnam HIV/AIDS treatment guidelines (P=0.02) and searching the scientific literature (P=0.09). Intervention participants outperformed controls on the exam (+23% vs +12% score gains, P=0.05) and had higher job satisfaction. CONCLUSION: The mCME V.2.0 intervention improved self-study behaviour, medical knowledge and job satisfaction. This approach has potential for expansion in Vietnam and similar settings. TRIAL REGISTRATION NUMBER: NCT02381743.

We don't dare to tell her we don't know where to begin: Disclosure experiences and challenges among adolescents living with HIV and their caregivers in China.

BACKGROUND AND OBJECTIVES: With increasing access to antiretroviral therapy, HIV-infected youth are living longer, but are vulnerable as they navigate the transition to adulthood while managing a highly stigmatized condition. Knowing one's HIV status is critical to assuming responsibility for one's health. The process of disclosure to adolescents living with HIV is not well understood globally, even less so in China. To help address this gap, we explored practices for disclosure to adolescents living with HIV (ALHIV) among Chinese caregivers and clinicians, and the disclosure experiences of the adolescents themselves using qualitative methods. DESIGN AND SETTING: The study was conducted in 2014 at the Guangxi Center for Disease Control and Prevention ART (CDC-ART) clinic in Nanning, China. We used a qualitative design, incorporating in-depth interviews (IDIs) and focus group discussions (FGDs). PATIENTS AND METHODS: We conducted IDIs with 19 adolescent/caregiver dyads and five FGDs with adolescents and clinicians. Adolescent participants were aged 10-15 years, and had contracted HIV perinatally. Using NVivoTM software, we summarized major themes. RESULTS: Only 6/19 caregivers reported disclosing to their child; matched adolescents' statements indicate that 9/19 children knew their HIV status. Caregivers planned to disclose when children were 14 years or older. Concerns about stigma toward children and families were associated with reluctance to disclose. CONCLUSION: Disclosure to adolescents living with HIV in China was delayed compared with recommended guidelines. Culturally appropriate disclosure strategies should be developed, focused on supporting caregivers and de-stigmatizing HIV.

A meta-analysis assessing all-cause mortality in HIV-exposed uninfected compared with HIV-unexposed uninfected infants and children.

OBJECTIVE: Conduct a meta-analysis examining differential all-cause mortality rates between HIV-exposed uninfected (HEU) infants and children as compared with their HIV-unexposed uninfected (HUU) counterparts. DESIGN: Meta-analysis summarizing the difference in mortality between HEU and HUU infants and children. Reviewed studies comparing children in the two groups for all-cause mortality, in any setting, from 1994 to 2016 from six databases. METHODS: Meta-analyses were done estimating overall mortality comparing the two groups, stratified by duration of follow-up time from birth (0-12, 12-24 and >24 months) and by year enrollment ended in each study: less than 2002 compared with at least 2002, when single-dose nevirapine for prevention of mother-to-child transmission (PMTCT) commenced in low-income and middle-income countries. RESULTS: Included 22 studies, for a total of 29 212 study participants [n = 8840 (30.3%) HEU; n = 20 372 (37.7%) HUU]. Random effects models showed HEU had a more than 70% increased risk of mortality vs. HUU. Stratifying by age showed that HEU vs. HUU had a significant 60-70% increased risk of death at every age strata. There was a significant 70% increase in the risk of mortality between groups before the implementation of PMTCT, which remained after 2002 [risk ratio: 1.46; 95% confidence interval (CI): 1.14-1.87], when the availability of PMTCT services was widespread, suggesting that prenatal antiretroviral therapy, and healthier mothers, does not fully eliminate this increased risk in mortality. CONCLUSION: We show a consistent increase risk of mortality for HEU vs. HUU infants and children. Longitudinal research is needed to elucidate underlying mechanisms, such as maternal and infant health status and breast feeding practices, which may help explain these differences in mortality.

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa.

BACKGROUND: In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ µl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies. METHODS: We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions. RESULTS: In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment). CONCLUSIONS: In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved.