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Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population.We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily.Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement.Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further.This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173.

What is already known about this topic? A novel HIV infection surveillance initiative was implemented in Malawi to collect data on recent HIV infections among new diagnoses to characterize the epidemic and guide the public health response. What is added by this report? Higher proportions of recent infections were identified among females, persons aged

BACKGROUND HIV population viral load (PVL) can reflect antiretroviral therapy program effectiveness and transmission potential in a community. Using nationally representative data from household surveys conducted in Zimbabwe, Malawi, and Zambia in 2015-16, we examined the association between various VL measures and the probability of at least one recent HIV-1 infection in the community. METHODS We used limiting-antigen avidity enzyme immunoassay, viral load suppression (VLS) (HIV RNA

BACKGROUND Early antiretroviral therapy (ART) is necessary for HIV epidemic control and depends on early diagnosis and successful linkage to care. Since 2014, annual household-based HIV testing and counseling and linkage services have been provided through the Chokwe Health and Demographic Surveillance System for residents testing HIV positive in this high HIV-burden district. METHODS District-wide Test and Start [T&S, ART for all people living with HIV (PLHIV)] began in August 2016, supported by systematic interventions to improve linkage to care and treatment. Annual rounds (R) of random household surveys were conducted to assess trends in population prevalence of ART use and viral load suppression (

The World Health Organization and national guidelines recommend HIV testing and counseling at tuberculosis (TB) clinics for all patients, regardless of TB diagnosis (1). Population-based HIV Impact Assessment (PHIA) survey data for 2015-2016 in Malawi, Zambia, and Zimbabwe were analyzed to assess HIV screening at TB clinics among persons who had positive HIV test results in the survey. The analysis was stratified by history of TB diagnosis* (presumptive versus confirmed†), awareness§ of HIV-positive status, antiretroviral therapy (ART)¶ status, and viral load suppression among HIV-positive adults, by history of TB clinic visit. The percentage of adults who reported having ever visited a TB clinic ranged from 4.7% to 9.7%. Among all TB clinic attendees, the percentage who reported that they had received HIV testing during a TB clinic visit ranged from 48.0% to 62.1% across the three countries. Among adults who received a positive HIV test result during PHIA and who did not receive a test for HIV at a previous TB clinic visit, 29.4% (Malawi), 21.9% (Zambia), and 16.2% (Zimbabwe) reported that they did not know their HIV status at the time of the TB clinic visit. These findings represent missed opportunities for HIV screening and linkage to HIV care. In all three countries, viral load suppression rates were significantly higher among those who reported ever visiting a TB clinic than among those who had not (p

IntroductionVoluntary medical male circumcision (VMMC), an effective HIV prevention programme for men, is implemented in East and Southern Africa. Approximately 50% of VMMC clients are aged below 15 years. More targeted interventions to reach older men and others at higher short-term HIV risk are needed.MethodsWe implemented a quality improvement project testing the effectiveness of an active referral-based VMMC recruitment approach, targeting men attending STI clinics and those escorting partners to antenatal care (ANC) clinics, at Bwaila Hospital in Lilongwe, Malawi. We compared the proportions aged older than 15 years among men who received VMMC following referral from STI and ANC clinics with those among men referred from standard community mobilisation. We also analysed referral cascades to VMMC.ResultsIn total, 330 clients were circumcised after referral from STI (242) and ANC (88) clinics, as compared with 3839 other clients attributed to standard community mobilisation. All clients from ANC and STI clinics were aged over 15 years, as compared with 69% from standard community mobilisation. STI clinics had a higher conversion rate from counselling to VMMC than ANC (12% vs 9%) and a higher contribution to total circumcisions performed at the VMMC clinic (6% vs 2%).ConclusionsIntegrating VMMC recruitment and follow-up in STI and ANC clinics co-located with VMMC services can augment demand creation and targeting of men at risk of HIV, based on age and STI history. This approach can be replicated at least in similar health facilities with ANC and STI services in close proximity to VMMC service delivery.

BACKGROUND To assist the Malawi Ministry of Health to evaluate 2 competing strategies for scale-up of isoniazid preventive therapy (IPT) among HIV-positive adults receiving antiretroviral therapy. SETTING Malawi. METHODS We used a multidistrict, compartmental model of the Malawi tuberculosis (TB)/HIV epidemic to compare the anticipated health impacts of 6-month versus continuous IPT programs over a 12-year horizon while respecting a US$10.8 million constraint on drug costs in the first 3 years. RESULTS The 6-month IPT program could be implemented nationwide, whereas the continuous IPT alternative could be introduced in 14 (of the 27) districts. By the end of year 12, the continuous IPT strategy was predicted to avert more TB cases than the 6-month alternative, although not statistically significant (2368 additional cases averted; 95% projection interval [PI], -1459 to 5023). The 6-month strategy required fewer person-years of IPT to avert a case of TB or death than the continuous strategy. For both programs, the mean reductions in TB incidence among people living with HIV by year 12 were expected to be

BackgroundClinical scores to determine early (6-month) antiretroviral therapy (ART) mortality risk have not been developed for sub-Saharan Africa (SSA), home to 70% of people living with HIV. In the absence of validated scores, WHO eligibility criteria (EC) for ART care intensification are CD4 MethodsWe used Botswana XPRES trial data for adult ART enrollees to develop CD4-independent and CD4-dependent multivariable prognostic models for 6-month mortality. Scores were derived by rescaling coefficients. Scores were developed using the first 50% of XPRES ART enrollees, and their accuracy validated internally and externally using South African TB Fast Track (TBFT) trial data. Predictive accuracy was compared between scores and WHO EC.ResultsAmong 5553 XPRES enrollees, 2838 were included in the derivation dataset; 68% were female and 83 (3%) died by 6 months. Among 1077 TBFT ART enrollees, 55% were female and 6% died by 6 months. Factors predictive of 6-month mortality in the derivation dataset atp 37.5 °C (2 points). The same variables plus CD4 ConclusionsSensitivity of the CD4-independent score was nearly twice that of WHO stage in predicting 6-month mortality and could be used in settings lacking CD4 testing to inform ART care intensification. The CD4-dependent score improved specificity versus WHO EC. Both scores should be considered for scale-up in SSA.

Twenty-two clinics providing HIV care and treatment in Botswana where tuberculosis (TB) and HIV comorbidity is as high as 49%.To assess eligibility of TB preventive treatment (TPT) at antiretroviral therapy (ART) initiation and at four follow-up visits (FUVs), and to describe the TB prevalence and associated factors at baseline and yield of TB diagnoses at each FUV.A prospective study of routinely collected data on people living with HIV (PLHIV) enrolled into care for the XpertOf 6041 PLHIV initiating ART, eligibility for TPT was 69% (4177/6041) at baseline and 93% (5408/5815); 95% (5234/5514); 96% (4869/5079); and 97% (3925/4055) at FUV1, FUV2, FUV3, and FUV4, respectively. TB prevalence at baseline was 11% and 2%, 3%, 3% and 6% at each subsequent FUV. At baseline, independent risk factors for prevalent TB were CD4200 cells/mmEligibility for TPT initiation is higher at visits post-ART initiation, while most cases of active TB were identified at ART initiation. Missed opportunities for TB further compromises TB control effort among PLHIV in Botswana.Veintidós consultorios que prestan atención y tratamiento relacionados con la infección por el virus de la inmunodeficiencia humana (VIH) en Botswana, donde la comorbilidad por tuberculosis (TB) e infección por el VIH puede alcanzar 49%.Evaluar los criterios para recibir el tratamiento preventivo de la TB (TPT) durante las consultas de iniciación y seguimiento del tratamiento antirretrovírico (TAR) y describir la prevalencia de TB y los factores asociados en el momento del inicio y el rendimiento del diagnóstico de TB en cada cita de seguimiento del TAR.Fue este un estudio prospectivo de los datos obtenidos sistemáticamente en las personas con infección por el VIH (PLHIV), inscritas en la atención para el estudio de evaluación del despliegue de la prueba XpertDe los 6041 PLHIV que iniciaron el TAR, 69% (4177/6041) cumplía los criterios para recibir el TPT al comienzo; 93% (5408/5815) en la primera consulta de seguimiento; 95% (5234/5514) en la segunda; 96% (4869/5079) en la tercera; y 97% (3925/4075) en la cuarta cita de seguimiento. La prevalencia inicial de TB fue 11% y durante el seguimiento fue 2%, 3%, 3% y 6%, respectivamente. Al comienzo del TAR, los factores de riesgo independientes de diagnóstico de TB fueron una cifra de linfocitos CD4200 células/mmLos pacientes cumplen las condiciones para recibir el TPT con mayor frecuencia en las consultas posteriores al comienzo del TAR, pero la mayoría de los casos de TB activa se detecta al iniciarlo. Las oportunidades desaprovechadas para detectar casos de TB dificultan aún más el control de esta enfermedad en las PLHIV en Botswana.

Background Undiagnosed tuberculosis (TB) remains the most common cause of HIV-related mortality. Xpert MTB/RIF (Xpert) is being rolled out globally to improve TB diagnostic capacity. However, previous Xpert impact trials have reported that health system weaknesses blunted impact of this improved diagnostic tool. During phased Xpert rollout in Botswana, we evaluated the impact of a package of interventions comprising (1) additional support for intensified TB case finding (ICF), (2) active tracing for patients missing clinic appointments to support retention, and (3) Xpert replacing sputum-smear microscopy, on early (6-month) antiretroviral therapy (ART) mortality. Methods At 22 clinics, ART enrollees > 12 years old were eligible for inclusion in three phases: a retrospective standard of care (SOC), prospective enhanced care (EC), and prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were implemented as a stepped-wedge trial. Participants in the EC phase received SOC plus components 1 (strengthened ICF) and 2 (active tracing) of the intervention package, and participants in the EC+X phase received SOC plus all three intervention package components. Primary and secondary objectives were to compare all-cause 6-month ART mortality between SOC and EC+X and between EC and EC+X phases, respectively. We used adjusted analyses, appropriate for study design, to control for baseline differences in individual-level factors and intra-facility correlation. Results We enrolled 14,963 eligible patients: 8980 in SOC, 1768 in EC, and 4215 in EC+X phases. Median age of ART enrollees was 35 and 64% were female. Median CD4 cell count was lower in SOC than subsequent phases (184/μL in SOC, 246/μL in EC, and 241/μL in EC+X). By 6 months of ART, 461 (5.3%) of SOC, 54 (3.2%) of EC, and 121 (3.0%) of EC+X enrollees had died. Compared with SOC, 6-month mortality was lower in the EC+X phase (adjusted hazard ratio, 0.77; 95% confidence interval, 0.61–0.97, p = 0.029). Compared with EC enrollees, 6-month mortality was similar among EC+X enrollees. Conclusions Interventions to strengthen ICF and retention were associated with lower early ART mortality. This new evidence highlights the need to strengthen ICF and retention in many similar settings. Similar to other trials, no additional mortality benefit of replacing sputum-smear microscopy with Xpert was observed. Trial registration Retrospectively registered: ClinicalTrials.gov (NCT02538952)

Funder: Joint United Nations Programme on HIV/AIDS; Id: http://dx.doi.org/10.13039/501100018734, Introduction: HIV planning requires granular estimates for the number of people living with HIV (PLHIV), antiretroviral treatment (ART) coverage and unmet need, and new HIV infections by district, or equivalent subnational administrative level. We developed a Bayesian small‐area estimation model, called Naomi, to estimate these quantities stratified by subnational administrative units, sex, and five‐year age groups. Methods: Small‐area regressions for HIV prevalence, ART coverage and HIV incidence were jointly calibrated using subnational household survey data on all three indicators, routine antenatal service delivery data on HIV prevalence and ART coverage among pregnant women, and service delivery data on the number of PLHIV receiving ART. Incidence was modelled by district‐level HIV prevalence and ART coverage. Model outputs of counts and rates for each indicator were aggregated to multiple geographic and demographic stratifications of interest. The model was estimated in an empirical Bayes framework, furnishing probabilistic uncertainty ranges for all output indicators. Example results were presented using data from Malawi during 2016–2018. Results: Adult HIV prevalence in September 2018 ranged from 3.2% to 17.1% across Malawi's districts and was higher in southern districts and in metropolitan areas. ART coverage was more homogenous, ranging from 75% to 82%. The largest number of PLHIV was among ages 35 to 39 for both women and men, while the most untreated PLHIV were among ages 25 to 29 for women and 30 to 34 for men. Relative uncertainty was larger for the untreated PLHIV than the number on ART or total PLHIV. Among clients receiving ART at facilities in Lilongwe city, an estimated 71% (95% CI, 61% to 79%) resided in Lilongwe city, 20% (14% to 27%) in Lilongwe district outside the metropolis, and 9% (6% to 12%) in neighbouring Dowa district. Thirty‐eight percent (26% to 50%) of Lilongwe rural residents and 39% (27% to 50%) of Dowa residents received treatment at facilities in Lilongwe city. Conclusions: The Naomi model synthesizes multiple subnational data sources to furnish estimates of key indicators for HIV programme planning, resource allocation, and target setting. Further model development to meet evolving HIV policy priorities and programme need should be accompanied by continued strengthening and understanding of routine health system data.

BACKGROUND Control of the pediatric HIV epidemic is hampered by gaps in diagnosis and linkage to effective treatment. The 2015-2016 Malawi Population-based HIV impact assessment data were analyzed to identify gaps in pediatric HIV diagnosis, treatment, and viral load suppression. METHODS In half of the surveyed households, children ages ≥18 months to

Background Identifying men living with HIV in sub-Saharan Africa (SSA) is critical to end the epidemic. We describe the underlying factors of unawareness among men aged 15-59 years who ever tested for HIV in 13 SSA countries. Methods Using pooled data from the nationally representative Population-based HIV Impact Assessments, we fit a log-binomial regression model to identify characteristics related to HIV positivity among HIV-positive unaware and HIV-negative men ever tested for HIV. Results A total of 114,776 men were interviewed and tested for HIV; 4.4% were HIV-positive. Of those, 33.7% were unaware of their HIV-positive status, (range: 20.2%-58.7%, in Rwanda and Cote d'Ivoire). Most unaware men reported they had ever received an HIV test (63.0%). Age, region, marital status, and education were significantly associated with HIV positivity. Men who had HIV-positive sexual partners (adjusted prevalence ratio [aPR]: 5.73; confidence interval [95% CI]: 4.13 to 7.95) or sexual partners with unknown HIV status (aPR: 2.32; 95% CI: 1.89 to 2.84) were more likely to be HIV-positive unaware, as were men who tested more than 12 months compared with HIV-negative men who tested within 12 months before the interview (aPR: 1.58; 95% CI: 1.31 to 1.91). Tuberculosis diagnosis and not being circumcised were also associated with HIV positivity. Conclusion Targeting subgroups of men at risk for infection who once tested negative could improve yield of testing programs. Interventions include improving partner testing, frequency of testing, outreach and educational strategies, and availability of HIV testing where men are accessing routine health services.

In 2017, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that worldwide, 36.9 million persons were living with human immunodeficiency virus (HIV) infection, the virus infection that causes acquired immunodeficiency syndrome (AIDS). Among persons with HIV infection, approximately 75% were aware of their HIV status, leaving 9.4 million persons with undiagnosed infection (1). Index testing, also known as partner notification or contact tracing, is an effective case-finding strategy that targets the exposed contacts of HIV-positive persons for HIV testing services. This report summarizes data from HIV tests using index testing in 20 countries supported by CDC through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) during October 1, 2016-March 31, 2018. During this 18-month period, 1,700,998 HIV tests with 99,201 (5.8%) positive results were reported using index testing. The positivity rate for index testing was 9.8% among persons aged ≥15 years and 1.5% among persons aged

Background Long-term viral load (VL) suppression among HIV-positive, reproductive-aged women on ART is key to eliminating mother-to-child transmission (MTCT) but few data exist from sub-Saharan Africa. We report trends in post-partum VL in Malawian women on ART and factors associated with detectable VL up to 24 months post-partum. Methods 1–6 months post-partum mothers, screened HIV-positive at outpatient clinics in Malawi, were enrolled (2014–2016) with their infants. At enrollment, 12- and 24-months post-partum socio-demographic and PMTCT indicators were collected. Venous samples were collected for determination of maternal VL (limit of detection 40 copies/ml). Results were returned to clinics for routine management. Results 596/1281 (46.5%) women were retained in the study to 24 months. Those retained were older (p Conclusions Detectable virus early post-partum strongly increases risk of ongoing post-partum viremia. Due to high loss to follow-up, the true incidence of detectable VL over time is probably underestimated. These findings have implications for MTCT, as well as for the mothers, and call for intensified VL monitoring and targeted adherence support for women during pregnancy and post-partum.

Background Isoniazid preventive therapy (IPT) against tuberculosis (TB) is a life-saving intervention for people living with HIV (PLHIV). In September 2017, Malawi began programmatic scale-up of IPT to eligible PLHIV in five districts with high HIV and TB burden. We measured the frequency and timeliness of early-phase IPT implementation to inform quality-improvement processes. Methods and findings We applied a two-stage cluster design with systematic, probability-proportional-to-size sampling of six U.S. Centers for Disease Control and Prevention (CDC)-affiliated antiretroviral therapy (ART) centers operating in the urban areas of Lilongwe and Blantyre, Malawi (November 2017). ART clinic patient volume determined cluster size. Within each cluster, we sequentially sampled approximately 50 PLHIV newly enrolled in ART care. We described a quality-of-care cascade for intensive TB case finding (ICF) and IPT in PLHIV. PLHIV newly enrolled in ART care were eligibility-screened for hepatitis and peripheral neuropathy, as well as for TB disease using a standardized four-symptom screening tool. Among eligible PLHIV, the overall weighted IPT initiation rate was 70% (95% CI: 46%–86%). Weighted IPT initiation among persons aged Conclusions Early-phase IPT uptake among adults at ART centers in Malawi was high. Child uptake needed improvement. National programs could adapt this framework to evaluate their ICF-IPT care cascades.

BackgroundPatients with non-tuberculous mycobacteria (NTM) or Mycobacterium tuberculosis (MTB) pulmonary disease may have similar clinical presentation. The potential for misdiagnosis and inappropriate treatment exists in settings with limited testing capacity for Xpert® MTB/RIF (Xpert), phenotypic culture and NTM speciation. We describe treatment outcomes among people living with HIV (PLHIV) who received anti-tuberculosis treatment and were found to have NTM or MTB positive sputum cultures.MethodsPLHIV attending one of the 22 participating HIV clinics, who screened positive for ≥1 tuberculosis (TB) symptoms (cough, fever, night sweats, or weight loss) were asked to submit sputa for culture and speciation from August 2012 to November 2014. The national intensified TB case finding algorithms were followed: initially symptomatic patients were evaluated by testing sputum samples using a smear (smear-based TB diagnostic algorithm) and, after GeneXpert instruments were installed, by testing with Xpert (Xpert-based TB diagnostic algorithm). Within the study period, TB diagnostic algorithms used for MTB did not include screening, diagnosis, and management of NTM. Despite MTB negative culture, some symptomatic patients, including those with NTM positive culture, received empirical anti-TB treatment at the discretion of treating clinicians. Per the World Health Organization treatment outcomes classification: died, treatment failure or loss-to-follow-up were classified as unfavorable (unsuccessful) outcome; cured and treatment completed were classified as favorable (successful) outcome. Empiric treatment was defined as initiating treatment without or before receiving a test result indicating MTB. We compare treatment outcomes and characteristics among patients with NTM or MTB positive culture who received anti-TB treatment.ResultsAmong 314 PLHIV, who were found co-infected with TB, 146 cases had microbiological evidence; and for 131/146 MTB positive cultures were reported. One-hundred fifty-two of the 314 were clinically diagnosed with TB and treated empirically. Among those empirically treated for TB, 36/152 had culture results positive for NTM, and another 43/152 had culture results positive for MTB, reported after patients received empirical anti-TB treatment. Overall, MTB positive culture results were reported for 174 (131 plus 43) patients. Treatment outcomes were available for 32/36 NTM and 139/174 MTB; unfavorable outcomes were 12.5% and 8.7% for NTM and MTB, respectively, p = 0.514, respectively. For 34/36 tested NTM patients, all Xpert results indicated 'no MTB'. Among patients who initially received empiric anti-TB treatment and ultimately were found to have MTB positive culture, the unfavorable outcome was 11.8% (4/34), compared to 12.5% (4/32) of patients with NTM positive culture, Fisher's exact test p = 1.00.ConclusionsWhile the higher unfavorable outcome was non statistically significant, the impact of inappropriate treatment among NTM patients should not be overlooked. Our findings suggest that Xpert has the potential to rapidly rule-out NTM and avoid sub-optimal treatment; further research is needed to evaluate such potential.

Twenty-two human immunodeficiency virus (HIV) clinics in Botswana.To compare sputum collection rates, sputum quality and volume, and tuberculosis (TB) diagnosis rates before and after field efforts to improve sputum collection among individuals newly diagnosed with HIV with TB symptoms.Newly diagnosed individuals living with HIV attending 22 HIV clinics in Botswana were screened for TB from August 2012 to March 2014. Starting in May 2013, a field intervention composed of the introduction of a tracking log for presumed TB patients, and patient instructions and sputum induction to improve sputum collection rates was implemented.Prior to the intervention, sputum collection rates were 44.1% (384/870). Subsequently, sputum collection increased to 58.3% (579/993) (Sputum collection rates among presumptive TB cases, as well as sputum quality and volume improved after implementation of the field intervention. To improve sputum collection rates, efforts at the program level should be ongoing.Vingt-deux dispensaires pour l’infection par le virus de l’immunodéficience humaine (VIH) au Botswana.Examiner les niveaux de qualité des crachats, leur volume, et le diagnostic de TB avant et après les efforts sur le terrain d’amélioration du recueil des crachats parmi les individus ayant récemment eu un diagnostic de VIH avec des symptômes de TB.Les personnes nouvellement diagnostiquées, vivant avec le VIH (PLHIV) fréquentant 22 dispensaires VIH au Botswana ont eu un dépistage de TB entre août 2012 et mars 2014. Les patients ayant des symptômes de TB ont été invités à fournir des échantillons de crachats. A partir de mai 2013, a été mise en œuvre une intervention de terrain composée de l’introduction d’un registre de suivi des patients présumés atteints de TB, de l’instruction du patient et de l’induction de crachats afin d’améliorer les taux de recueil de crachats. Les taux de recueil de crachats, leur qualité, leur volume et le rendement ont été comparés avant et après l’intervention.Avant l’intervention, les taux de recueil des crachats ont été de 44,1% (384/870). Le recueil de crachats a ensuite augmenté à 58,3% (579/993) (Les taux de recueil de crachats parmi les cas de TB présumés ainsi que la qualité et le volume des crachats se sont améliorés après la mise en œuvre de l’intervention sur le terrain. Des efforts continus sont cependant requis au niveau du programme afin d’améliorer les taux de recueil des crachats.Veintidós consultorios de atención de la infección por el virus de la inmunodeficiencia humana (VIH) en Botswana.Examinar la calidad y el volumen de las muestras de esputo y el diagnóstico de tuberculosis (TB) antes y después de ejecutar iniciativas sobre el terreno encaminadas a mejorar la recolección de esputo, en personas con diagnóstico reciente de infección por el VIH que presentan síntomas indicativos de TB.Se realizó el tamizaje de la TB en las personas con diagnóstico reciente de infección por el VIH que acudieron a 22 consultorios de atención de la infección por el VIH en Botswana, de agosto del 2012 a marzo del 2014. Se solicitaron muestras de esputo a los pacientes con síntomas de TB. A partir de mayo del 2013, se llevó a cabo una intervención sobre el terreno que comportaba la introducción de un registro de rastreo de los pacientes con presunción de tuberculosis, instrucciones a los pacientes y la inducción del esputo con el fin de mejorar las tasas de recolección de muestras de esputo. Se compararon las tasas de obtención de muestras, su calidad y su volumen antes y después de la intervención.La tasa de recolección de esputo fue 44,1% (384/870) antes de la intervención y 58,3% (579/993) después de la misma (Tras la introducción de una intervención sobre el terreno se mejoró la tasa de obtención de muestras de esputo, su calidad y su volumen en los casos con presunción de TB. Se precisan no obstante esfuerzos permanentes a escala programática que mejoren las tasas de recolección.

Tests for recent HIV infection (TRI) distinguish recent from long-term HIV infections using markers of antibody maturation. The limiting antigen avidity enzyme immunoassay (LAg EIA) is widely used with HIV viral load (VL) in a recent infection testing algorithm (RITA) to improve classification of recent infection status, estimate population-level HIV incidence, and monitor trends in HIV transmission. A novel rapid test for recent HIV infection (RTRI), Asanté™, can determine HIV serostatus and HIV recency within minutes on a lateral flow device through visual assessment of test strip or reader device. We conducted a field-based laboratory evaluation of the RTRI among pregnant adolescent girls and young women (AGYW) attending antenatal clinics (ANC) in Malawi.We enrolled pregnant AGYW aged 90% and >0.65 respectively indicating substantial agreement between the RITAs.This was the first field evaluation of an RTRI in sub-Saharan Africa, which demonstrated good performance of the assay and feasibility of integrating RTRI into routine HIV testing services for real-time surveillance of recent HIV infection.

In 2017, rapid human immunodeficiency virus (HIV) testing services enabled the HIV diagnosis and treatment of approximately 15.3 million persons with HIV infection in sub-Saharan Africa with life-saving antiretroviral therapy (ART) (1). Although suboptimal testing practices and misdiagnoses have been reported in sub-Saharan Africa and elsewhere, trends in population burden and rate of false positive HIV diagnosis (false diagnosis) have not been reported (2,3). Understanding the population prevalence and trends of false diagnosis is fundamental for guiding rapid HIV testing policies and practices. To help address this need, CDC analyzed data from 57,655 residents aged 15–59 years in the Chókwè Health and Demographic Surveillance System (CHDSS) in Mozambique to evaluate trends in the rate (the percentage of false diagnoses among retested persons reporting a prior HIV diagnosis) and population prevalence of false diagnosis. From 2014 to 2017, the observed rate of false diagnosis in CHDSS decreased from 0.66% to 0.00% (p

Routine data from Malawi's prevention of mother-to-child transmission (MTCT) option B+ programme suggest high uptake of antiretroviral therapy (ART) among pregnant women. Malawi's Ministry of Health led the National Evaluation of Malawi's PMTCT Program to obtain nationally representative data on maternal ART coverage and prevention of MTCT effectiveness. Here, we present the early transmission data for infants aged 4-12 weeks.We used a multistage cluster design to recruit a nationally representative sample of HIV-exposed infants and their mothers in Malawi. Between October 16, 2014, and May 17, 2016, we screened for HIV in all mothers attending an under-5 vaccination or outpatient sick-child clinic with infants aged 4-26 weeks at 54 health facilities selected across ten districts and four regional sampling zones. Infants with mothers identified as HIV-infected were enrolled in the cohort. We calculated weighted MTCT rates for only the subset of infants aged 4-12 weeks at screening, thereby capturing MTCT from early pregnancy, to delivery, and early breastfeeding. We collected data on maternal and infant demographics and self-reported use of HIV services, ART, and antenatal clinics. We tested HIV-exposed infants for the virus and assessed associations of certain variables with infant HIV status.We confirmed HIV exposure in 3542 (10·4%) of 33 980 mother (guardian)-infant pairs with infants aged 4-26 weeks. Of those, 2530 (2514 mothers and 16 guardians) had infants aged 4-12 weeks at the time of screening (2498 singlets and 32 twins). We excluded 25 infants from the analysis because no information was available about their HIV status. 91·3% (95% CI 85·6-96·9) of mothers were on ART during pregnancy. The MTCT rate was 3·7% (2·3-6·0) overall and ranged from 1·4% (0·4-4·4) in women who initiated ART before pregnancy to 19·9% (13·4-28·6) in women not on ART. In multivariable logistic regression analysis, the odds of early MTCT were higher in mothers starting ART post partum (adjusted odds ratio 16·7, 95% CI 1·6-171·5; p=0·022) and in those not on ART with an unknown HIV status during pregnancy (19·1, 8·5-43·0; p0·0001) than in mothers on ART before pregnancy. Among HIV-exposed infants, 98·0% (95% CI 96·9-99·1) were reported by the mother to have received infant nevirapine prophylaxis, and only 45·6% (34·8-56·4) were already enrolled in an exposed infant HIV care clinic at the time of study screening.These data suggest that Malawi's decentralisation of ART services has resulted in higher ART coverage and lower early MTCT. However, the uptake of services for HIV-exposed infants remains suboptimal.President's Emergency Plan for AIDS Relief.

To achieve epidemic control of human immunodeficiency virus (HIV) infection, sub-Saharan African countries are striving to diagnose 90% of HIV infections, initiate and retain 90% of HIV-diagnosed persons on antiretroviral therapy (ART), and achieve viral load suppression* for 90% of ART recipients (90-90-90) (1). In Eswatini (formerly Swaziland), the country with the world's highest estimated HIV prevalence (27.2%), achieving 90-90-90 depends upon improving access to early ART for men and young adults with HIV infection, two groups with low ART coverage (1-3). Although community-based strategies test many men and young adults with HIV infection in Eswatini, fewer than one third of all persons who test positive in community settings enroll in HIV care within 6 months of diagnosis after receiving standard referral services (4,5). To evaluate the effectiveness of peer-delivered linkage case management† in improving early ART initiation for persons with HIV infection diagnosed in community settings in Eswatini, CDC analyzed data on 651 participants in CommLink, a community-based, mobile HIV-testing, point-of-diagnosis HIV care, and peer-delivered linkage case management demonstration project, and found that after diagnosis, 635 (98%) enrolled in care within a median of 5 days (interquartile range [IQR] = 2-8 days), and 541 (83%) initiated ART within a median of 6 days (IQR = 2-14 days), including 402 (74%) on the day of their first clinic visit (same-day ART). After expanding ART eligibility to all persons with HIV infection on October 1, 2016, 96% of 225 CommLink clients initiated ART, including 87% at their first clinic visit. Compared with women and adult clients aged ≥30 years, similar high proportions of men and persons aged 15-29 years enrolled in HIV care and received same-day ART. To help achieve 90-90-90 by 2020, the United States President's Emergency Plan for AIDS Relief (PEPFAR) is supporting the national scale-up of CommLink in Eswatini and recommending peer-delivered linkage case management as a potential strategy for countries to achieve >90% early enrollment in care and ART initiation after diagnosis of HIV infection (6).

Background Among people living with HIV (PLHIV), more flexible and sensitive tuberculosis (TB) screening tools capable of detecting both symptomatic and subclinical active TB are needed to (1) reduce morbidity and mortality from undiagnosed TB; (2) facilitate scale-up of tuberculosis preventive therapy (TPT) while reducing inappropriate prescription of TPT to PLHIV with subclinical active TB; and (3) allow for differentiated HIV–TB care. Methods and findings We used Botswana XPRES trial data for adult HIV clinic enrollees collected during 2012 to 2015 to develop a parsimonious multivariable prognostic model for active prevalent TB using both logistic regression and random forest machine learning approaches. A clinical score was derived by rescaling final model coefficients. The clinical score was developed using southern Botswana XPRES data and its accuracy validated internally, using northern Botswana data, and externally using 3 diverse cohorts of antiretroviral therapy (ART)-naive and ART-experienced PLHIV enrolled in XPHACTOR, TB Fast Track (TBFT), and Gugulethu studies from South Africa (SA). Predictive accuracy of the clinical score was compared with the World Health Organization (WHO) 4-symptom TB screen. Among 5,418 XPRES enrollees, 2,771 were included in the derivation dataset; 67% were female, median age was 34 years, median CD4 was 240 cells/μL, 189 (7%) had undiagnosed prevalent TB, and characteristics were similar between internal derivation and validation datasets. Among XPHACTOR, TBFT, and Gugulethu cohorts, median CD4 was 400, 73, and 167 cells/μL, and prevalence of TB was 5%, 10%, and 18%, respectively. Factors predictive of TB in the derivation dataset and selected for the clinical score included male sex (1 point), ≥1 WHO TB symptom (7 points), smoking history (1 point), temperature >37.5°C (6 points), body mass index (BMI) 10) yielded TB prevalence of 1%, 1%, 2%, and 6% in the lowest risk group and 33%, 22%, 26%, and 32% in the highest risk group for XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively. At clinical score ≥2, the number needed to screen (NNS) ranged from 5.0 in Gugulethu to 11.0 in XPHACTOR. Limitations include that the risk score has not been validated in resource-rich settings and needs further evaluation and validation in contemporary cohorts in Africa and other resource-constrained settings. Conclusions The simple and feasible clinical score allowed for prioritization of sensitivity and NPV, which could facilitate reductions in mortality from undiagnosed TB and safer administration of TPT during proposed global scale-up efforts. Differentiation of risk by clinical score cutoff allows flexibility in designing differentiated HIV–TB care to maximize impact of available resources., Andrew Auld and colleagues evaluate a clinical score for active tuberculosis in persons with HIV infection., Author summary Why was this study done? Tuberculosis (TB) remains the most common cause of death among people living with HIV (PLHIV) and is often undiagnosed at time of death. Rapid scale-up of tuberculosis preventive therapy (TPT) to 13 million PLHIV in low- and middle-income countries (LMICs) has been proposed for 2021; however, active TB is commonly asymptomatic and therefore missed by current WHO-recommended 4-symptom TB screening rules. Therefore, more sensitive TB screening tools are needed to better facilitate early TB diagnosis and safer scale-up of TPT to PLHIV by avoiding TPT prescription to clients with asymptomatic active TB, who need TB treatment. What did the researchers do and find? We derived a TB risk score for PLHIV from XPRES trial data and validated the score on 3 external datasets. We prioritized high sensitivity and ability to correctly rule out TB (i.e., high negative predictive value (NPV)) at key time points in care such as HIV clinic enrollment and before TPT prescription. Both logistic regression and random forest machine learning approaches were used to identify the 6 most important predictors, commonly available in LMIC clinic settings. In the external datasets, TB risk score ≥2 had higher sensitivity (87% to 97%) than WHO 4-symptom screening rule and increased NPV by 0.3% to 1.7%. Three risk groups were identified by the score, with active TB prevalence in external datasets ranging from 1% to 6% in the lowest to 22% to 32% in the highest risk groups. What do these findings mean? Following further validation, this clinical score could improve early detection of active TB to reduce morbidity and mortality from undiagnosed TB. Use of the clinical score cutoff of ≥2 during the proposed TPT scale-up for 13 million PLHIV could potentially avoid many thousands of PLHIV with active TB being inappropriately prescribed TPT. By differentiating 3 risk groups, the score also allows for the development of differentiated service delivery models suitable for LMIC.

Monitoring retention of people living with HIV (PLHIV) in the HIV care and treatment cascade is essential to guide program strategy and evaluate progress toward globally-endorsed 90–90–90 targets (i.e., 90% of PLHIV diagnosed, 81% on sustained antiretroviral therapy (ART), and 73% virally suppressed). We describe national retention from diagnosis throughout the cascade for patients receiving HIV services in Haiti during 1985–2015, with a focus on those receiving HIV services during 2008–2015. Among the 266,256 newly diagnosed PLHIV during 1985–2015, 49% were linked-to-care, 30% started ART, and 18% were retained on ART by the time of database closure. Similarly, among the 192,187 newly diagnosed HIV-positive patients during 2008–2015, 50% were linked to care, 31% started ART, and 19% were retained on ART by the time of database closure. Most patients (90–92%) at all cascade steps were adults (≥ 15 years old), among whom the majority (60–61%) were female. During 2008–2015, outcomes varied significantly across 42 administrative districts (arrondissements) of residence; cumulative linkage-to-care ranged from 23% to 69%, cumulative ART initiation among care enrollees ranged from 2% to 80%, and cumulative ART retention among ART enrollees ranged from 30% to 88%. Compared with adults, children had lower cumulative incidence of ART initiation among care enrollees (64% versus 47%) and lower cumulative retention among ART enrollees (64% versus 50%). Cumulative linkage-to-care was low and should be prioritized for improvement. Variations in outcomes by arrondissement and between adults and children require further investigation and programmatic response.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count

Background Xpert® MTB/RIF (Xpert) has high sensitivity for diagnosing tuberculosis (TB) compared to sputum-smear microscopy (smear) and can reduce time-to-diagnosis, time-to-treatment and potentially unfavorable patient-level treatment outcome. Methods People living with HIV (PLHIV) initiating antiretroviral therapy at 22 HIV clinics were enrolled and underwent systematic screening for TB (August 2012–November 2014). GeneXpert instruments were deployed following a stepped-wedge design at 13 centers from October 2012–June 2013. Treatment outcomes classified as an unfavorable outcome (died, treatment failure or loss-to-follow-up) or favorable outcome (cured and treatment completed). To determine outcome, smear was performed at month 5 or 6. Empiric treatment was defined as initiating treatment without/before receiving TB-positive results. Adjusting for intra-facility correlation, we compared patient-level treatment outcomes between patients screened using smear (smear arm)- and Xpert-based algorithms (Xpert arm). Results Among 6041 patients enrolled (smear arm, 1816; Xpert arm, 4225), 256 (199 per 2985 and 57 per 1582 person-years of follow-up in Xpert and smear arms, respectively; adjusted incidence rate ratio, 9.07; 95% confidence interval [CI]: 4.70–17.48; p p = 0.268). Compared to smear, in Xpert arm median days from sputum collection to TB treatment was 6 days (interquartile range [IQR] 2–17 versus 22 days [IQR] 3–51), p = 0.005; patients with available sputum test result had microbiologically confirmed TB in 59.0% (102/173) versus 41.9% (18/43), adjusted Odds Ratio [aOR], 2.00, 95% CI: 1.01–3.96, p = 0.048). In smear arm empiric treatment was 68.4% (39/57) versus 48.7% (97/199), aOR, 2.28, 95% CI: 1.24–4.20, p = 0.011), compared to Xpert arm. Conclusions TB treatment outcomes were similar between the smear and Xpert arms. However, compared to the smear arm, more patients in the Xpert arm received a TB diagnosis, had a microbiologically confirmed TB, and had a shorter time-to-treatment, and had a lower empiric treatment. Further research is recommended to identify potential gaps in the Botswana health system and similar settings. Trial registration ClinicalTrials.gov Identifier: NCT02538952. Retrospectively registered on 2 September 2015.

BACKGROUND: Compared with smear microscopy, Xpert® MTB/RIF has the potential to reduce delays in tuberculosis (TB) diagnosis and treatment initiation, and improve treatment outcomes. We reviewed publications comparing treatment outcomes of drug-susceptible TB patients diagnosed using Xpert vs. smear. METHODS: Citations (2000–2016) reporting treatment outcomes of patients diagnosed using Xpert compared with smear were selected from PubMed, Scopus and conference abstracts. We conducted a systematic review and meta-analysis. Favorable (cured, completed) and unfavorable (failure, death, loss to follow-up) outcomes were pooled for meta-analysis; we also reviewed the number of TB cases diagnosed, time to treatment and empiric treatment. The Mantel-Haenszel method with a fixed-effect model was used; I(2) was calculated to measure heterogeneity. RESULTS: From 13 citations, 43 594 TB patients were included and 4825 were with known TB treatment outcome. From the pooled analysis, an unfavorable outcomes among those diagnosed using Xpert compared with smear was 20.2%, 541/2675 vs. 21.9%, 470/2150 (risk ratio 0.92, 95%CI 0.82–1.02). Statistical heterogeneity was low (I(2) = 0.0%, P = 0.910). Compared with smear, Xpert was reported to be superior in increasing the number of TB patients diagnosed (2/9 citations), increasing bacteriologically confirmed TB (7/9 citations), reducing empiric treatment (3/5 citations), reducing time to diagnosis (2/3 citations), and reducing time to treatment initiation (1/5 citations). CONCLUSIONS: Xpert implementation showed no discernible impact on treatment outcomes compared with conventional smear despite reduced time to diagnosis, time to treatment or reduced level of empiric treatment. Further research is required to learn more about gaps in the existing health system.

During 2004-2013 in Mozambique, 455,600 HIV-positive adults (≥15 years old) initiated antiretroviral therapy (ART). We evaluated trends in patient characteristics and outcomes during 2004-2013, outcomes of universal treatment for pregnant women (Option B+) implemented since 2013, and effect on outcomes of distributing ART to stable patients through Community ART Support Groups (CASG) since 2010.Data for 306,335 adults starting ART during 2004-2013 at 170 ART facilities were analyzed. Mortality and loss to follow-up (LTFU) were estimated using competing risks models. Outcome determinants were estimated using proportional hazards models, including CASG participation as a time-varying covariate.Compared with ART enrollees in 2004, enrollees in 2013 were more commonly female (55% vs. 73%), more commonly pregnant if female (1% vs. 30%), and had a higher median baseline CD4 count (139 vs. 235/μL). During 2004-2013, observed 6-month mortality declined from 7% to 2% but LTFU increased from 24% to 30%. Pregnant women starting ART with CD4 count350/μL and WHO stage I/II under Option B+ guidelines in 2013 had low 6-month mortality (0.1%) but high 6-month LTFU (38%). During 2010-2013, 6766 patients joined CASGs. In multivariable analysis, compared with nonparticipation in CASG, CASG participation was associated with 35% lower LTFU but similar mortality.Initiation of ART at earlier disease stages in later calendar years might explain observed declines in mortality. Retention interventions are needed to address trends of increasing LTFU overall and the high LTFU among Option B+ pregnant women specifically. Further expansion of CASG could help reduce LTFU.

Background Virologic failure (VF) is highly prevalent in sub-Saharan African children on antiretroviral therapy (ART) and is often associated with human immunodeficiency virus drug resistance (DR). Most children still lack access to routine viral load (VL) monitoring for early identification of treatment failure, with implications for the efficacy of second-line ART. Methods Children aged 1 to 14 years on ART for ≥12 months at 6 public facilities in Maputo, Mozambique were consecutively enrolled after informed consent. Chart review and caregiver interviews were conducted. VL testing was performed, and specimens with ≥1000 copies/mL were genotyped. Results Of the 715 children included, the mean age was 103 months, 85.8% had no immunosuppression, 73.1% were taking stavudine/lamivudine/nevirapine, and 20.1% had a history prevention of mother-to-child transmission exposure. The mean time on ART was 60.0 months. VF was present in 259 patients (36.3%); 248 (95.8%) specimens were genotyped, and DR mutations were found in 238 (96.0%). Severe immunosuppression and nutritional decline were associated with DR. M184V and Y181C were the most common mutations. In the 238 patients with DR, standard second-line ART would have 0, 1, 2, and 3 effective antiretrovirals in 1 (0.4%), 74 (31.1%), 150 (63.0%), and 13 (5.5%) patients, respectively. Conclusion This cohort had high rates of VF and DR with frequent compromise of second-line ART. There is urgent need to scale-up VL monitoring and heat-stable protease inhibitor formulations or integrase inhibitorsfor a more a durable first-line regimen that can feasibly be implemented in developing settings.

Introduction In 2011, Malawi implemented “Option B+,” a test‐and‐treat strategy for the prevention of maternal to child transmission of HIV (PMTCT); however limited data on viral load (VL) suppression exist. We describe VL suppression in HIV‐infected women at four to twenty‐six weeks postpartum, factors associated with VL suppression and the impact of VL suppression levels on MTCT. Methods HIV‐positive mothers at four to twenty‐six weeks postpartum were enrolled in a nested cross‐sectional study within the “National Evaluation of Malawi's PMTCT Programme” cohort study between October 2014 and May 2016. HIV‐exposed infants received HIV‐1 DNA testing and venous samples determined maternal VL, classified as unsuppressed (>1000 copies/mL), low‐detectable (40 to 1000 copies/mL) or undetectable (

INTRODUCTION: The World Health Organization endorsed (2010) the use of Xpert MTB/RIF and countries are shifting from smear microscopy (smear)-based to Xpert MTB/RIF-based tuberculosis (TB) diagnostic algorithms. As with smear, sputum quality may predict the likelihood of obtaining a bacteriologically-confirmed TB when using Xpert MTB/RIF. METHODS: From 08/12-11/2014, all people living with HIV were recruited at 22 clinics. For patients screened positive using the four TB symptoms their sputa were tested by Xpert MTB/RIF and smear. Laboratorians assessed and recorded sputum appearance and volume. The yield of bacteriologically-positive sputum evaluated using Xpert MTB/RIF and smear, likelihood-ratios were calculated. RESULTS: Among 6,041 patients enrolled 2,296 were presumptive TB, 1,305 (56.8%) had > 1 sputa collected and 644/1,305 (49.3%) had both Xpert MTB/RIF and smear results. Since >1 sputa collected from 644 patients 954 sputa were tested by Xpert MTB/RIF and smear. Bacteriologically-positive sputum was two-fold higher with Xpert MTB/RIF 11.4% versus smear 5.3%, p < 0.001. Sputum appearance and quantity were not predictive of bacteriologically-positive results, except volume of 2ml to < 3ml, tested by Xpert MTB/RIF LR+=1.26 (95% CI, 1.05–1.50). CONCLUSION: Xpert MTB/RIF test yield to bacteriologically-positive sputum was superior to smear. Sputum quality and quantity, however, were not consistently predictive of bacteriologically-positive results by Xpert MTB/RIF or smear.

In 2016, an estimated 1.5 million females aged 15-24 years were living with human immunodeficiency virus (HIV) infection in Eastern and Southern Africa, where the prevalence of HIV infection among adolescent girls and young women (3.4%) is more than double that for males in the same age range (1.6%) (1). Progress was assessed toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2020 targets for adolescent girls and young women in sub-Saharan Africa (90% of those with HIV infection aware of their status, 90% of HIV-infected persons aware of their status on antiretroviral treatment [ART], and 90% of those on treatment virally suppressed [HIV viral load

BACKGROUND During 2004-2009, >12,000 children (

Background Antiretroviral therapy (ART) for HIV-infected sex workers is an important HIV prevention strategy. However, sex workers may have additional challenges for retention in ART care. The objectives of this study were to assess retention of sex workers on ART in a routine setting in Ivory Coast and identify risk factors for loss to follow-up (LTFU). Methods The design was a retrospective cohort study. An analysis of clinic files was conducted in 2 sites providing ART services to sex workers in Ivory Coast. Demographic, behavior, and clinical data of female and male sex workers on ART were abstracted onto a standardized anonymous data collection form. Data collection took place between May 11 and 28, 2010. Results A total of 376 female and 38 male sex workers were included in the analysis. The retention probability was 75% at 6 months, 68% at 12 months, 55% at 24 months, and 47% at 36 months. Attrition was mainly because of LTFU. Factors significantly associated with LTFU in bivariate analysis were lower schooling level, later calendar year of starting ART, and not receiving initial adherence counseling. Later year of starting ART and not receiving adherence counseling at ART initiation remained significantly associated with LTFU in a multivariate Cox regression model. Conclusions To improve the retention of sex workers on ART, there is a need for more in-depth investigation of the role of pre-ART counseling and the increasing rates of LTFU with each calendar year.

Objectives: To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa. Design: A cross-sectional study. Methods: Systematically selected ART clients (>= 18 years; on ART >= 6 months) attending 18facilities in three countries (250 clients/facility) were interviewed. Client self-reports (3-day, 30-day, Case Index >= 48 consecutive hours of missed ART), healthcare provider estimates and the pharmacymedication possession ratio(MPR) were used to estimate ART adherence. Participants from two facilities per country underwent HIV RNA testing. Optimal adherence measures were selected on the basis of degree of association with concurrent HIV RNA dichotomized at less than or greater/equal to 1000 copies/ml. Multivariate regression analysis, adjusted for site-level clustering, assessed associations between incomplete adherence and individual and programme factors. Results: A total of 4489 participants were included, of whom 1498 underwent HIV RNA testing. Nonadherence ranged from 3.2% missing at least 48 consecutive hours to 40.1% having an MPR of less than 90%. The percentage with HIV RNA at least 1000 copies/ml ranged from 7.2 to 17.2% across study sites (mean = 9.9%). Having at least 48 consecutive hours of missed ART was the adherence measure most strongly related to virologic failure. Factors significantly related to incomplete adherence included visiting a traditional healer, screening positive for alcohol abuse, experiencing more HIV symptoms, having an ART regimen without nevirapine and greater levels of internalized stigma. Conclusion: Results support more in-depth investigations of the role of traditional healers, and the development of interventions to address alcohol abuse and internalized stigma among treatment-experienced adult ART patients. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

Background In 2011, the Botswana National Tuberculosis Program adopted World Health Organization guidelines and introduced Xpert MTB/RIF (Xpert) assay to support intensified case finding among people living with HIV enrolling in care. An evaluation was designed to assess performance under operational conditions to inform the national Xpert scale-up. Methods Xpert was implemented from August 2012 through November 2014 with 13 GeneXpert instruments (GeneXpert) deployed in a phased approach over nine months: nine centralized laboratory and four point-of-care (POC) peripheral clinics. Clinicians and laboratorians were trained on the four-symptom tuberculosis screening algorithm and Xpert testing. We documented our experience with staff training and GeneXpert performance. Test results were extracted from GeneXpert software; unsuccessful tests were analysed in relation to testing sites and trends over time. Results During 276 instrument-months of operation a total of 3,630 tests were performed, of which 3,102 (85%) were successful with interpretable results. Mycobacterium tuberculosis complex was detected for 447 (14%); of these, 36 (8%) were rifampicin resistant. Of all 3,630 Xpert tests, 528 (15%) were unsuccessful; of these 361 (68%) were classified as “error”, 119 (23%) as “invalid” and 48 (9%) as “no result”. The total number of recorded error codes was 385 and the most common reasons were related to sample processing (211; 55%) followed by power supply (77; 20%) and cartridge/module related (54; 14%). Cumulative incidence of unsuccessful test was similar between POC (17%, 95% CI: 11–25%) and centralized laboratory-based GeneXpert instruments (14%, 95% CI: 11–17%; p = 0.140). Conclusions Xpert introduction was successful in the Botswana setting. The incidence of unsuccessful test was similar by GeneXpert location (POC vs. centralized laboratory). However, unsuccessful test incidence (15%) in our settings was higher than previously reported and was mostly related to improper sample processing. Ensuring adequate training among Xpert testing staff is essential to minimize errors.

[This corrects the article DOI: 10.1371/journal.pone.0165528.].

Background Non-tuberculous mycobacteria (NTM) can cause pulmonary infection and disease especially among people living with HIV (PLHIV). PLHIV with NTM disease may clinically present with one of the four symptoms consistent with tuberculosis (TB). We describe the prevalence of NTM and Mycobacterium tuberculosis complex (MTBC) isolated among PLHIV who presented for HIV care and treatment. Methods All PLHIV patients presenting for HIV care and treatment services at 22 clinical sites in Botswana were offered screening for TB and were recruited. Patients who had ≥1 TB symptom were asked to submit sputa for Xpert MTB/RIF and culture. Culture growth was identified as NTM and MTBC using the SD-Bioline TB Ag MPT64 Kit and Ziehl Neelsen microscopy. NTM and MTBC isolates underwent species identification by the Hain GenoType CM and AS line probe assays. Results Among 16, 259 PLHIV enrolled 3068 screened positive for at least one TB symptom. Of these, 1940 submitted ≥1 sputum specimen, 427 (22%) patients had ≥1 positive-culture result identified phenotypically for mycobacterial growth. Of these 247 and 180 patients were identified as having isolates were NTM and MTBC, respectively. Of the 247 patients identified with isolates containing NTM; 19 were later excluded as not having NTM based on additional genotypic testing. Among the remaining 408 patients 228 (56%, 95% confidence interval, 46–66%) with NTM. M. intracellulare was the most common isolated (47.8%). Other NTMs commonly associated with pulmonary disease included M. malmoense (3.9%), M. avium (2.2%), M. abscessus (0.9%) and M. kansasii (0.4%). After excluding NTM isolates that were non-speciated and M. gordonae 154 (67.5%) of the NTM isolates were potential pathogens. Conclusions In the setting of HIV care and treatment, over-half (56%) of a positive sputum culture among PLHIV with TB symptoms was NTM. Though we were not able to distinguish in our study NTM disease and colonization, the study suggests culture and species identification for PLHIV presenting with TB symptoms remains important to facilitate NTM diagnosis and hasten time to appropriate treatment.