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ObjectivesWe assessed retention and predictors of attrition (recorded death or loss to follow-up) in antiretroviral treatment (ART) clinics in Tanzania, Uganda and Zambia. MethodsWe conducted a retrospective cohort study among adults (18years) starting ART during 2003-2010. We purposefully selected six health facilities per country and randomly selected 250 patients from each facility. Patients who visited clinics at least once during the 90days before data abstraction were defined as retained. Data on individual and programme level risk factors for attrition were obtained through chart review and clinic manager interviews. Kaplan-Meier curves for retention across sites were created. Predictors of attrition were assessed using a multivariable Cox-proportional hazards model, adjusted for site-level clustering. ResultsFrom 17 facilities, 4147 patients were included. Retention ranged from 52.0% to 96.2% at 1year to 25.8%-90.4% at 4years. Multivariable analysis of ART initiation characteristics found the following independent risk factors for attrition: younger age [adjusted hazard ratio (aHR) and 95% confidence interval (95%CI)=1.30 (1.14-1.47)], WHO stage 4 ([aHR (95% CI): 1.56 (1.29-1.88)], >10% bodyweight loss [aHR (95%CI)=1.17 (1.00-1.38)], poor functional status [ambulatory aHR (95%CI)=1.29 (1.09-1.54); bedridden aHR1.54 (1.15-2.07)], and increasing years of clinic operation prior to ART initiation in government facilities [aHR (95%CI)=1.17 (1.10-1.23)]. Patients with higher CD4 cell count were less likely to experience attrition [aHR (95%CI)=0.88 (0.78-1.00)] for every log (tenfold) increase. Sites offering community ART dispensing [aHR (95%CI)=0.55 (0.30-1.01) for women; 0.40 (0.21-0.75) for men] had significantly less attrition. ConclusionsPatient retention to an individual programme worsened over time especially among males, younger persons and those with poor clinical indicators. Community ART drug dispensing programmes could improve retention. ObjectifsNous avons evalue la retention et les predicteurs de l'attrition (deces ou pertes au suivi enregistres) dans le traitement antiretroviral (ART) dans des cliniques en Tanzanie, en Ouganda et en Zambie. MethodesNous avons mene une etude de cohorte retrospective chez les adultes (18 ans) ayant debute l'ART au cours de 2003-2010. Nous avons deliberement choisi six etablissements de sante par pays et avons choisi au hasard 250 patients dans chaque etablissement. Les patients qui ont visite les cliniques au moins une fois au cours des 90 jours avant l'extraction des donnees ont ete definis comme retenus. Les donnees sur les facteurs de risque individuels et a l'echelle du programme pour l'attrition ont ete obtenues par l'examen des dossiers et des entrevues avec les directeur des cliniques. Les courbes de Kaplan-Meier pour la retention a travers les sites ont ete creees. Les predicteurs de l'attrition ont ete evalues a l'aide d'un modele multivarie des risques proportionnels de Cox, corriges par le regroupement au niveau du site. ResultatsDe 17 etablissements, 4147 patients ont ete inclus. La retention variait de 52,0% a 96,2% a un an et de 25,8% a 90,4% a 4 ans. L'analyse multivariee des caracteristiques a l'initiation de l'ART a trouve les facteurs independants de risque pour l'attrition suivants: le plus jeune age [Hazard Ratio ajuste (aHR) et intervalle de confiance a 95% (IC 95%)=1,30 (1,14 a 1,47)], le stade 4 de l'OMS ([aHR (IC 95%): 1,56 (1,29 a 1,88)], > 10% de perte de poids corporel [aHR (IC 95%)=1,17 (1,00 a 1,38)], un mauvais etat fonctionnel [aHR ambulatoire=1,29 (1,09-1,54); aHR alite=1,54 (01,15 a 02,07)] et de plus en plus d'annees d'operations en clinique avant le debut de l'ART dans les etablissements publics [aHR(IC 95%)=1,17 (1,10 a 1,23)]. Les patients avec un taux plus eleve de cellules CD4 etaient moins susceptibles a l'attrition [aHR (IC 95%) = 0,88 (0,78 a 1,00)] pour chaque augmentation logarithmique. Les sites offrant la distribution communautaire de l'ART [aHR (IC 95%)=0,55 (0,30 a 1,01) pour les femmes; =0,40 (0,21 a 0,75) pour les hommes] avaient significativement moins d'attrition. ConclusionsLa retention des patients dans un programme individuel empirait au fil du temps surtout chez les hommes, les personnes plus jeunes et ceux avec de mauvais indicateurs cliniques. Les programmes de distribution communautaire de l'ART pourraient ameliorer la retention. ObjetivosHemos evaluado la retencion y los vaticinadores de abandono (muerte registrada o perdida durante el seguimiento) en centros de tratamiento antirretroviral (TAR) en Tanzania, Uganda y Zambia. MetodosHemos realizado un estudio retrospectivo de cohortes con adultos (18 anos) en TAR durante el 2003-2010. Seleccionamos seis centros sanitarios por pais, y de forma aleatoria a 250 pacientes de cada centro. Los pacientes que visitaron los centros al menos una vez durante los 90 dias anteriores a la fecha de obtencion de los datos se definieron como retenidos. Se obtuvieron datos sobre los factores de riesgo de abandono de los individuos y el nivel del programa mediante la revision de graficos y entrevistas con el gestor del centro. Se realizaron curvas de Kaplan-Meier para la retencion en los distintos centros. Los vaticinadores de abandono se evaluaron utilizando un modelo de riesgos proporcionales de Cox, ajustado para agrupacion a nivel de centros. ResultadosSe incluyeron 4147 pacientes de 17 centros. La retencion estaba entre 52.0%-96.2% al ano y 25.8%-90.4% a los 4 anos. En un analisis multivariante de las caracteristicas presentes en el momento de iniciar TAR, se encontraron los siguientes factores de riesgo de abandono independientes: ser mas joven [razon de riesgo ajustada (RRa) and IC 95=1.30 (1.14-1.47)], estadio 4 de la OMS ([RRa(IC 95%): 1.56 (1.29-1.88)], > 10% perdida de peso corporal [RRa (IC 95%)=1.17 (1.00-1.38)], un estatus funcional pobre [RRa ambulatorio (IC 95%)=1.29 (1.09-1.54); estar en cama RRa 1.54 (1.15-2.07) ], y un mayor numero de anos en clinicas privadas antes de comenzar TAR en un centro gubernamental [RRa (IC 95%)=1.17 (1.10-1.23)]. Los pacientes con un mayor conteo de CD4 tenian una menor probabilidad de experimentar abandono [RRa (IC 95%)=0.88 (0.78-1.00)] para un aumento logaritmico (x10). Los centros que ofrecian dispensarios comunitarios de TAR [aHR (IC95%)=0.55 (0.30-1.01) para mujeres; 0.40 (0.21-0.75) para hombres] tenian significativamente menos abandono. ConclusionesLa retencion de pacientes en un programa individual empeoro a lo largo del tiempo, especialmente entre los hombres, personas jovenes y aquellos con indicadores clinicos pobres. Los programas comunitarios de dispensacion de TAR podrian mejorar la retencion.

SETTING In Cote d'Ivoire, more than 2000 human immunodeficiency virus (HIV) infected children aged

Objective To describe associations between childhood violence and forced sexual initiation in young Malawian females. Study design We analyzed data from 595 women and girls who were 13-24 years old who ever had sex and participated in Malawi's 2013 Violence Against Children Survey, a nationally representative household survey. We estimated the overall prevalence of forced sexual initiation and identified subgroups with highest prevalences. Using logistic regression, we examined childhood violence and other independent predictors of forced sexual initiation. Results The overall prevalence of forced sexual initiation was 38.9% among Malawian girls and young women who ever had sex. More than one-half of those aged 13-17 years at time of survey (52.0%), unmarried (64.6%), or experiencing emotional violence in childhood (56.9%) reported forced sexual initiation. After adjustment, independent predictors of forced sexual initiation included being unmarried (aOR, 3.54; 95% CI, 1.22-10.27) and any emotional violence (aOR, 2.47; 95% CI, 1.45-4.24). Those experiencing emotional violence alone (aOR, 3.04; 95% CI: 1.01-9.12), emotional violence in combination with physical or nonpenetrative sexual violence (aOR, 2.50; 95% CI, 1.23-5.09), and emotional violence in combination with physical and nonpenetrative sexual violence (aOR, 2.61; 95% CI, 1.20-5.67) had an increased independent odds of forced sexual initiation. Conclusions Experiences of forced sexual initiation are common among Malawian females. Emotional violence is strongly associated with forced sexual initiation, alone and in combination with other forms of childhood violence. The relationship between emotional violence and forced sexual initiation highlights the importance of comprehensive strategies to prevent childhood violence.

Objective To measure the association between the number of doctors, nurses and hospital beds per 10,000 people and individual HIV-infected patient outcomes in Botswana. Design Analysis of routinely collected longitudinal data from 97,627 patients who received ART through the Botswana National HIV/AIDS Treatment Program across all 24 health districts from 2002 to 2013. Doctors, nurses, and hospital bed density data at district-level were collected from various sources. Methods A multilevel, longitudinal analysis method was used to analyze the data at both patient- and district-level simultaneously to measure the impact of the health system input at district-level on probability of death or loss-to-follow-up (LTFU) at the individual level. A marginal structural model was used to account for LTFU over time. Results Increasing doctor density from one doctor to two doctors per 10,000 population decreased the predicted probability of death for each patient by 27%. Nurse density changes from 20 nurses to 25 nurses decreased the predicted probability of death by 28%. Nine percent decrease was noted in predicted mortality of an individual in the Masa program for every five hospital bed density increase. Conclusion Considerable variation was observed in doctors, nurses, and hospital bed density across health districts. Predictive margins of mortality and LTFU were inversely correlated with doctor, nurse and hospital bed density. The doctor density had much greater impact than nurse or bed density on mortality or LTFU of individual patients. While long-term investment in training more healthcare professionals should be made, redistribution of available doctors and nurses can be a feasible solution in the short term.

BACKGROUND In 2007, Swaziland initiated a hub-and-spoke model for decentralizing antiretroviral therapy (ART) access for HIV-infected children (

Background High rates of attrition are stymying Mozambique’s national HIV Program’s efforts to achieve 80% treatment coverage. In response, Mozambique implemented a national pilot of Community Adherence and Support Groups (CASG). CASG is a model in which antiretroviral therapy (ART) patients form groups of up to six patients. On a rotating basis one CASG group member collects ART medications at the health facility for all group members, and distributes those medications to the other members in the community. Patients also visit their health facility bi-annually to receive clinical services. Methods A matched retrospective cohort study was implemented using routinely collected patient-level data in 68 health facilities with electronic data systems and CASG programs. A total of 129,938 adult ART patients were registered in those facilities. Of the 129,938 patients on ART, 6,760 were CASG members. A propensity score matched analysis was performed to assess differences in mortality and loss to follow-up (LTFU) between matched CASG and non-CASG members. Propensity scores were estimated using a random-effects logistic regression model. The following covariates where included in the model: sex, educational status, WHO stage, year of ART initiation, age, CASG eligibility, CD4 cell count category, weight, and employment status. Results Non-CASG participants had higher LTFU rates (HR 2.356; p = 0.04) than matched CASG participants; however, there were no significant mortality differences between CASG and non-CASG participants. Compared with the full cohort of non-CASG members, CASG members were more likely to be female (74% vs. 68%), tended to have a lower median CD4 counts at ART initiation (183 cells/m3 vs. 200cells/m3) and be less likely to have a secondary school education (15% vs. 23%). Conclusion ART patients enrolled in CASG were significantly less likely to be LTFU compared to matched patients who did not join CASG. CASG appears to be an effective strategy to decrease LTFU in Mozambique’s national ART program.

Objectives To identify the reasons patients miss taking their antiretroviral therapy (ART) and the proportion who miss their ART because of symptoms; and to explore the association between symptoms and incomplete adherence. Methods Secondary analysis of data collected during a cross-sectional study that examined ART adherence among adults from 18 purposefully selected sites in Tanzania, Uganda, and Zambia. We interviewed 250 systematically selected patients per facility (>= 18 years) on reasons for missing ART and symptoms they had experienced (using the HIV Symptom Index). We abstracted clinical data from the patients' medical, pharmacy, and laboratory records. Incomplete adherence was defined as having missed ART for at least 48 consecutive hours during the past 3 months. Results Twenty-nine percent of participants reported at least one reason for having ever missed ART (1278/4425). The most frequent reason was simply forgetting (681/1278 or 53%), followed by ART-related hunger or not having enough food (30%), and symptoms (12%). The median number of symptoms reported by participants was 4 (IQR: 2-7). Every additional symptom increased the odds of incomplete adherence by 12% (OR: 1.1, 95% CI: 1.1-1.2). Female participants and participants initiated on a regimen containing stavudine were more likely to report greater numbers of symptoms. Conclusions Symptoms were a common reason for missing ART, together with simply forgetting and food insecurity. A combination of ART regimens with fewer side effects, use of mobile phone text message reminders, and integration of food supplementation and livelihood programmes into HIV programmes, have the potential to decrease missed ART and hence to improve adherence and the outcomes of ART programmes.

Objective To evaluate the variation in all-cause attrition (mortality and loss to follow-up (LTFU)) among HIV-infected individuals in Botswana by health district during the rapid and massive scale-up of the National Treatment Program. Methods Analysis of routinely collected longitudinal data from 226030 patients who received ART through the Botswana National HIV/AIDS Treatment Program across all 24 health districts from 2002 to 2013. A time-to-event analysis was used to measure crude mortality and loss to follow-up rates (LTFU). A marginal structural model was used to evaluate mortality and LTFU rates by district over time adjusted for individual-level risk factors (e.g. age gender baseline CD4 year of treatment initiation and antiretroviral regimen). Results Mortality rates in the districts ranged from the lowest 1.0 (95% CI 0.9-1.1) in Selibe-Phikwe to the highest 5.0 (95% CI 4.0-6.1) in Mabutsane. There was a wide range of overall LTFU across districts including rates as low as 4.6 (95% CI 4.4-4.9) losses per 100 person-years in Ngamiland and 5.9 (95% CI 5.6-6.2) losses per 100 person-years in South East to rates as high as 25.4 (95% CI 23.08-27.89) losses per 100 person-years in Mabutsane and 46.3 (95% CI 43.48-49.23) losses per 100 person-years in Okavango. Even when known risk factors for mortality and LTFU were adjusted for district was a significant predictor of both mortality and LTFU rates Conclusion We found statistically significant variation in attrition (mortality and LTFU) and data quality among districts. These findings suggest that district-level contextual factors affect retention in treatment. Further research needs to investigate factors that can potentially cause this variation.

BACKGROUND: In 2007 Swaziland initiated a hub-and-spoke model for decentralizing antiretroviral therapy (ART) access. Decentralization was facilitated through (1) down-referral of stable ART patients from overburdened central facilities (hubs) to primary health care clinics (spokes) and (2) ART initiation at spokes (spoke initiation). METHODS: We conducted a nationally representative retrospective cohort study among adult ART enrollees during 2004-2010 to assess the effect of down-referral and spoke-initiation on rates of loss to follow-up (LTFU) death and attrition (death or LTFU). Sixteen of 31 hubs were randomly selected using probability-proportional-to-size sampling. Seven selected facilities had initiated the hub-and-spoke model by study start. At these facilities 1149 of 24782 hub-initiated and maintained and 878 of 7722 down-referred or spoke-initiated patient records were randomly selected and analyzed. At the 9 hub-only facilities 483 of 6638 records were randomly selected and analyzed. Multivariable proportional hazards regression was used to assess effect of down-referral (a time-varying covariate) and spoke-initiation on outcomes. RESULTS: At ART initiation median age was 35 65% were female and median CD4 count was 147 cells per microliter. Controlling for known confounders down-referral was strongly protective against LTFU [adjusted hazard ratio (AHR) 0.38; 95% confidence interval (CI): 0.29 to 0.50] and attrition (AHR = 0.50; 95% CI: 0.34 to 0.76) but not mortality. Compared with hub-initiated and maintained patients spoke-initiated patients had lower LTFU (AHR 0.59; 95% CI: 0.45 to 0.77) and attrition rates (AHR 0.60; 95% CI: 0.47 to 0.77) but not mortality. CONCLUSIONS: Down-referral and spoke-initiation within a hub-and-spoke ART decentralization model were protective against LTFU and overall attrition and could facilitate future ART program expansion.

Since 1996, widespread availability of combination antiretroviral therapy (ART) has significantly improved survival of HIV-infected persons in industrialized countries. This has prompted researchers in Europe and North America to investigate whether mortality among HIV-infected persons receiving ART might reach levels similar to those in the general population. In this paper by Lewden et al., more than 80 000 patients from 31 European countries are included in an analysis to estimate crude ART patient mortality rates for persons 518 years of age, who initiated ART during 1998–2008, had a known gender and date of birth, known baseline CD4þ T-cell (CD4) count, and 51 follow-up visit. The standardized mortality ratio (SMR) is used to compare mortality between ART patients and the general population. The SMR is the ratio of the observed number of deaths in the ART cohorts to the expected number of deaths if ART cohorts had experienced general population country-, calendar-year-, gender-, and age-specific mortality. SMRs were estimated using random effects Poisson models, adjusted for age, gender, HIV transmission group and history of AIDS at ART start. The overall ART patient mortality rate of 1.2 per 100 person years (PY) is similar to that recently reported for 13 cohorts from nine countries in Europe and North America (0.95/100 PY for the period 2001– 2009) and 23 cohorts from 10 European countries, Australia and Canada (0.86/100 PY for the period 2004–2006), supporting previous estimates that average annual risk of death for ART patients has declined since 1996–2001, when estimates of about 3/100 PY were reported. The authors were specifically interested in assessing whether ART patient mortality could reach levels similar to those experienced in the general population, if ART patients achieved and maintained CD4 counts 5500/mm. This article builds on previous work by Lewden et al. in 2007, which reported that ART patients in a French cohort, who maintained CD4 counts 5500/mm, had mortality rates similar to those of the general population 6 years after ART start. In this analysis, only certain subgroups of patients who achieved CD4 counts 5500/mm reached mortality rates similar to those observed in the general population. First, among all male ART patients, who achieved and maintained a CD4 count 5500/mm for 53 years, mortality was similar to that of males in the general population [SMR 1.0, 95% confidence interval (CI) 0.8–1.4]. In contrast, mortality among all female ART patients, who achieved a CD4 count 5500/mm, was always higher than that of females in the general population, even after 5 years with a CD4 count 5500/mm. Higher SMRs among females compared with males has been documented in other studies. Authors suggest that differences in the prevalence of low socio-economic status (SES) and/ or smoking between HIV-infected and uninfected persons may be more pronounced for females than males and this might explain the higher SMRs for females. Adjustment of SMRs for SES indicators and smoking burden, variables not available to authors for this analysis, would be needed to further investigate SMR differences by sex. Secondly, among the subgroup of non-injection drug users (non-IDUs) with a CD4 count 5500/mm, males immediately on achieving this CD4 threshold (SMR 0.9, 95% CI 0.7–1.2), and females after 3 years in this CD4 stratum (SMR 1.1, 95% CI 0.7–1.7), had similar mortality rates to those in the Published by Oxford University Press on behalf of the International Epidemiological Association 2012. International Journal of Epidemiology 2012;1–2

High rates of attrition are stymying Mozambique's national HIV Program's efforts to achieve 80% treatment coverage. In response, Mozambique implemented a national pilot of Community Adherence and Support Groups (CASG). CASG is a model in which antiretroviral therapy (ART) patients form groups of up to six patients. On a rotating basis one CASG group member collects ART medications at the health facility for all group members, and distributes those medications to the other members in the community. Patients also visit their health facility bi-annually to receive clinical services.A matched retrospective cohort study was implemented using routinely collected patient-level data in 68 health facilities with electronic data systems and CASG programs. A total of 129,938 adult ART patients were registered in those facilities. Of the 129,938 patients on ART, 6,760 were CASG members. A propensity score matched analysis was performed to assess differences in mortality and loss to follow-up (LTFU) between matched CASG and non-CASG members. Propensity scores were estimated using a random-effects logistic regression model. The following covariates where included in the model: sex, educational status, WHO stage, year of ART initiation, age, CASG eligibility, CD4 cell count category, weight, and employment status.Non-CASG participants had higher LTFU rates (HR 2.356; p = 0.04) than matched CASG participants; however, there were no significant mortality differences between CASG and non-CASG participants. Compared with the full cohort of non-CASG members, CASG members were more likely to be female (74% vs. 68%), tended to have a lower median CD4 counts at ART initiation (183 cells/m3 vs. 200cells/m3) and be less likely to have a secondary school education (15% vs. 23%).ART patients enrolled in CASG were significantly less likely to be LTFU compared to matched patients who did not join CASG. CASG appears to be an effective strategy to decrease LTFU in Mozambique's national ART program.

Background Nigeria had the most AIDS-related deaths worldwide in 2014 (170,000), and 46% were associated with tuberculosis (TB). Although treatment of people living with HIV (PLHIV) with antiretroviral therapy (ART) reduces TB-associated morbidity and mortality, incident TB can occur while on ART. We estimated incidence and characterized factors associated with TB after ART initiation in Nigeria. Methods We analyzed retrospective cohort data from a nationally representative sample of adult patients on ART. Data were abstracted from 3,496 patient records, and analyses were weighted and controlled for a complex survey design. We performed domain analyses on patients without documented TB disease and used a Cox proportional hazard model to assess factors associated with TB incidence after ART. Results At ART initiation, 3,350 patients (95.8%) were not receiving TB treatment. TB incidence after ART initiation was 0.57 per 100 person-years, and significantly higher for patients with CD4

BACKGROUND: During 2004-2008 >2000 children (

Background In Cote d’Ivoire, tuberculosis (TB) is a common cause of death among HIV-infected antiretroviral therapy (ART) enrollees. Ivorian guidelines recommend screening for TB and initiation of TB treatment before ART initiation. Compliance with these guidelines can help reduce TB-related mortality during ART and possibly nosocomial TB transmission. Methods and Findings In a retrospective cohort study among 3,682 randomly selected adults (≥15 years old) starting ART during 2004–2007 at 34 randomly selected facilities, documentation of TB screening completion, prevalence of active TB at ART initiation, and incidence of TB during ART were evaluated. At ART initiation, median age was 36 years, 67% were female, and median CD4 count was 135 cells/μL. Among all 3,682 enrollees, 73 (2%) were on TB treatment at the time of referral to the ART facility. Among the 3,609 not on TB treatment, 1,263 (36%) were documented to receive some TB screening before ART initiation; 21% were screened for cough, 21% for weight loss, 18% for fever, 18% for TB contacts, and 12% for night sweats. Among the 1,263 screened, 111 (11%) were diagnosed with TB and started TB treatment before ART. No associations between patient characteristics and probability of being screened were noted. However, documentation of TB screening completion before ART varied widely by ART facility from 0–100%. TB incidence during ART was 3.0 per 100 person-years but varied widely by ART facility from 0/100 person-year to 13.1/100 person-years. Conclusions Screening for TB before ART initiation was poorly documented. Facility-level variations in TB screening documentation suggest facility-level factors, such as investment in training programs, might determine documentation practices. Targeting under-performing ART facilities with improvement activities is needed. Variations among facilities in TB incidence warrant further research. These incidence variations could reflect differences between facilities in TB screening, diagnostic tests, documentation practices, or TB risk possibly related to infection control practices or local community TB incidence.

Objectives: To determine the incidence and risk factors of mortality for all HIV-infected patients receiving antiretroviral treatment at public and private healthcare facilities in the Botswana National HIV/AIDS Treatment Programme.

Background In Cote d'Ivoire during 2004–2007, numbers of ART enrollees increased from

Background In Mozambique, tuberculosis (TB) is thought to be the most common cause of death among antiretroviral therapy (ART) enrollees. Monitoring proportions of enrollees screened for TB, and incidence and determinants of TB during ART can help clinicians and program managers identify program improvement opportunities. Methodology/Principal Findings We conducted a retrospective cohort study among a nationally representative sample of the 79,500 adults (>14 years old) initiating ART during 2004–2007 to estimate clinician compliance with TB screening guidelines, factors associated with active TB at ART initiation, and incidence and predictors of documented TB during ART follow-up. Of 94 sites enrolling >50 adults on ART, 30 were selected using probability-proportional-to-size sampling; 2,596 medical records at these sites were randomly selected for abstraction and analysis. At ART initiation, median age of patients was 34, 62% were female, median baseline CD4+ T-cell count was 153/µL, and 11% were taking TB treatment. Proportions of records with TB screening documentation before ART initiation improved from 31% to 66% during 2004–2007 (p

BACKGROUND: In Mozambique during 2004-2007 numbers of adult patients (≥15 years old) enrolled on antiretroviral therapy (ART) increased about 16-fold, from 60 kg), WHO stage IV (AHR 1.7; 95% CI, 1.3-2.4, reference group WHO stage I/II), lack of co-trimoxazole prescription (AHR 1.4; 95% CI, 1.0-1.8), and later calendar year of ART initiation (AHR 1.5; 95% CI, 1.2-1.8). Rates of immunologic treatment failure and regimen-switch were 14.0 and 0.6 events per 100-patient years, respectively. CONCLUSIONS: ART initiation at earlier disease stages and scale-up of co-trimoxazole among ART patients could improve outcomes. Research to determine reasons for low regimen-switch rates and increasing rates of attrition during program expansion is needed.

Background In 2012, as a pilot for Botswana’s national Xpert MTB/RIF (Xpert) rollout plans, intensified tuberculosis (TB) case finding (ICF) activities were strengthened at 22 HIV treatment clinics prior to phased activation of 13 Xpert instruments. Together, the strengthened ICF intervention and Xpert activation are referred to as the “Xpert package”. Methods The evaluation, called the Xpert Package Rollout Evaluation using a Stepped-wedge design (XPRES), has two key objectives: (1) to compare sensitivity of microscopy-based and Xpert-based pulmonary TB diagnostic algorithms in diagnosing sputum culture-positive TB; and (2) to evaluate impact of the “Xpert package” on all-cause, 6-month, adult antiretroviral therapy (ART) mortality. A pragmatic, stepped-wedge cluster-randomized trial design was chosen. The design involves enrollment of three cohorts: (1) cohort R, a retrospective cohort of all study clinic ART enrollees in the 24 months before study initiation (July 31, 2012); (2) cohort A, a prospective cohort of all consenting patients presenting to study clinics after study initiation, who received the ICF intervention and the microscopy-based TB diagnostic algorithm; and (3) cohort B, a prospective cohort of all consenting patients presenting to study clinics after Xpert activation, who received the ICF intervention and the Xpert-based TB diagnostic algorithm. TB diagnostic sensitivity will be compared between TB culture-positive enrollees in cohorts A and B. All-cause, 6-month ART-mortality will be compared between cohorts R and B. With anticipated cohort R, A, and B sample sizes of about 10,131, 1,878, and 4,258, respectively, the study is estimated to have >80 % power to detect differences in pre-versus post-Xpert TB diagnostic sensitivity if pre-Xpert sensitivity is ≤52.5 % and post-Xpert sensitivity ≥82.5 %, and >80 % power to detect a 40 % reduction in all-cause, 6-month, ART mortality between cohorts R and B if cohort R mortality is ≥13/100 person-years. Discussion Only one small previous trial (N = 424) among ART enrolees in Zimbabwe evaluated, in a secondary analysis, Xpert impact on all-cause 6-month ART mortality. No mortality impact was observed. This Botswana trial, with its larger sample size and powered specifically to detect differences in all-cause 6-month ART mortality, remains well-positioned to contribute understanding of Xpert impact. Trial registration Retrospectively registered at ClinicalTrials.gov: NCT02538952. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1905-4) contains supplementary material, which is available to authorized users.