From Paper Files to Web-Based Application for Data-Driven Monitoring of HIV Programs: Nigeria's Journey to a National Data Repository for Decision-Making and Patient Care.

BACKGROUND: Timely and reliable data are crucial for clinical, epidemiologic, and program management decision making. Electronic health information systems provide platforms for managing large longitudinal patient records. Nigeria implemented the National Data Repository (NDR) to create a central data warehouse of all people living with human immunodeficiency virus (PLHIV) while providing useful functionalities to aid decision making at different levels of program implementation. OBJECTIVE: We describe the Nigeria NDR and its development process, including its use for surveillance, research, and national HIV program monitoring toward achieving HIV epidemic control. METHODS: Stakeholder engagement meetings were held in 2013 to gather information on data elements and vocabulary standards for reporting patient-level information, technical infrastructure, human capacity requirements, and information flow. Findings from these meetings guided the development of the NDR. An implementation guide provided common terminologies and data reporting structures for data exchange between the NDR and the electronic medical record (EMR) systems. Data from the EMR were encoded in extensible markup language and sent to the NDR over secure hypertext transfer protocol after going through a series of validation processes. RESULTS: By June 30, 2021, the NDR had up-to-date records of 1,477,064 (94.4%) patients receiving HIV treatment across 1,985 health facilities, of which 1,266,512 (85.7%) patient records had fingerprint template data to support unique patient identification and record linkage to prevent registration of the same patient under different identities. Data from the NDR was used to support HIV program monitoring, case-based surveillance and production of products like the monthly lists of patients who have treatment interruptions and dashboards for monitoring HIV test and start. CONCLUSION: The NDR enabled the availability of reliable and timely data for surveillance, research, and HIV program monitoring to guide program improvements to accelerate progress toward epidemic control.

Low-level viraemia among people living with HIV in Nigeria: a retrospective longitudinal cohort study.

BACKGROUND: HIV transmission can occur with a viral load of at least 200 copies per mL of blood and low-level viraemia can lead to virological failure; the threshold level at which risk for virological failure is conferred is uncertain. To better understand low-level viraemia prevalence and outcomes, we analysed retrospective longitudinal data from a large cohort of people living with HIV on antiretroviral therapy (ART) in Nigeria. METHODS: In this retrospective cohort study using previously collected longitudinal patient data, we estimated rates of virological suppression (≤50 copies per mL), low-level viraemia (51-999 copies per mL), virological non-suppression (≥1000 copies per mL), and virological failure (≥2 consecutive virological non-suppression results) among people living with HIV aged 18 years and older who initiated and received at least 24 weeks of ART at 1005 facilities in 18 Nigerian states. We analysed risk for low-level viraemia, virological non-suppression, and virological failure using log-binomial regression and mixed-effects logistic regression. FINDINGS: At first viral load for 402 668 patients during 2016-21, low-level viraemia was present in 64 480 (16·0%) individuals and virological non-suppression occurred in 46 051 (11·4%) individuals. Patients with low-level viraemia had increased risk of virological failure (adjusted relative risk 2·20, 95% CI 1·98-2·43; p<0·0001). Compared with patients with virological suppression, patients with low-level viraemia, even at 51-199 copies per mL, had increased odds of low-level viraemia and virological non-suppression at next viral load; patients on optimised ART (ie, integrase strand transfer inhibitors) had lower odds than those on non-integrase strand transfer inhibitors for the same low-level viraemia range (eg, viral load ≥1000 copies per mL following viral load 400-999 copies per mL, integrase strand transfer inhibitor: odds ratio 1·96, 95% CI 1·79-2·13; p<0·0001; non-integrase strand transfer inhibitor: 3·21, 2·90-3·55; p<0·0001). INTERPRETATION: Patients with low-level viraemia had increased risk of virological non-suppression and failure. Programmes should revise monitoring benchmarks and targets from less than 1000 copies per mL to less than 50 copies per mL to strengthen clinical outcomes and track progress to epidemic control. FUNDING: None.

Protecting the gains: analysis of HIV treatment and service delivery programme data and interventions implemented in 19 African countries during COVID-19.

INTRODUCTION: The potential disruption in antiretroviral therapy (ART) services in Africa at the start of the COVID-19 pandemic raised concern for increased morbidity and mortality among people living with HIV (PLHIV). We describe HIV treatment trends before and during the pandemic and interventions implemented to mitigate COVID-19 impact among countries supported by the US Centers for Disease Control and Prevention (CDC) through the President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: We analysed quantitative and qualitative data reported by 10,387 PEPFAR-CDC-supported ART sites in 19 African countries between October 2019 and March 2021. Trends in PLHIV on ART, new ART initiations and treatment interruptions were assessed. Viral load coverage (testing of eligible PLHIV) and viral suppression were calculated at select time points. Qualitative data were analysed to summarize facility- and community-based interventions implemented to mitigate COVID-19. RESULTS: The total number of PLHIV on ART increased quarterly from October 2019 (n = 7,540,592) to March 2021 (n = 8,513,572). The adult population (≥15 years) on ART increased by 14.0% (7,005,959-7,983,793), while the paediatric population (<15 years) on ART declined by 2.6% (333,178-324,441). However, the number of new ART initiations dropped between March 2020 and June 2020 by 23.4% for adults and 26.1% for children, with more rapid recovery in adults than children from September 2020 onwards. Viral load coverage increased slightly from April 2020 to March 2021 (75-78%) and viral load suppression increased from October 2019 to March 2021 (91-94%) among adults and children combined. The most reported interventions included multi-month dispensing (MMD) of ART, community service delivery expansion, and technology and virtual platforms use for client engagement and site-level monitoring. MMD of ≥3 months increased from 52% in October 2019 to 78% of PLHIV ≥ age 15 on ART in March 2021. CONCLUSIONS: With an overall increase in the number of people on ART, HIV programmes proved to be resilient, mitigating the impact of COVID-19. However, the decline in the number of children on ART warrants urgent investigation and interventions to prevent further losses experienced during the COVID-19 pandemic and future public health emergencies.

Expanding access to HIV services during the COVID-19 pandemic-Nigeria, 2020.

BACKGROUND: To accelerate progress toward the UNAIDS 90-90-90 targets, US Centers for Disease Control and Prevention Nigeria country office (CDC Nigeria) initiated an Antiretroviral Treatment (ART) Surge in 2019 to identify and link 340,000 people living with HIV/AIDS (PLHIV) to ART. Coronavirus disease 2019 (COVID-19) threatened to interrupt ART Surge progress following the detection of the first case in Nigeria in February 2020. To overcome this disruption, CDC Nigeria designed and implemented adapted ART Surge strategies during February-September 2020. METHODS: Adapted ART Surge strategies focused on continuing expansion of HIV services while mitigating COVID-19 transmission. Key strategies included an intensified focus on community-based, rather than facility-based, HIV case-finding; immediate initiation of newly-diagnosed PLHIV on 3-month ART starter packs (first ART dispense of 3 months of ART); expansion of ART distribution through community refill sites; and broadened access to multi-month dispensing (MMD) (3-6 months ART) among PLHIV established in care. State-level weekly data reporting through an Excel-based dashboard and individual PLHIV-level data from the Nigeria National Data Repository facilitated program monitoring. RESULTS: During February-September 2020, the reported number of PLHIV initiating ART per month increased from 11,407 to 25,560, with the proportion found in the community increasing from 59 to 75%. The percentage of newly-identified PLHIV initiating ART with a 3-month ART starter pack increased from 60 to 98%. The percentage of on-time ART refill pick-ups increased from 89 to 100%. The percentage of PLHIV established in care receiving at least 3-month MMD increased from 77 to 93%. Among PLHIV initiating ART, 6-month retention increased from 74 to 92%. CONCLUSIONS: A rapid and flexible HIV program response, focused on reducing facility-based interactions while ensuring delivery of lifesaving ART, was critical in overcoming COVID-19-related service disruptions to expand access to HIV services in Nigeria during the first eight months of the pandemic. High retention on ART among PLHIV initiating treatment indicates immediate MMD in this population may be a sustainable practice. HIV program infrastructure can be leveraged and adapted to respond to the COVID-19 pandemic.

Optimizing community linkage to care and antiretroviral therapy Initiation: Lessons from the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) and their adaptation in Nigeria ART Surge.

BACKGROUND: Ineffective linkage to care (LTC) is a known challenge for community HIV testing. To overcome this challenge, a robust linkage to care strategy was adopted by the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). The NAIIS linkage to care strategy was further adapted to improve Nigeria's programmatic efforts to achieve the 1st 90 as part of the Nigeria Antiretroviral Therapy (ART) Surge initiative, which also included targeted community testing. In this paper we provide an overview of the NAIIS LTC strategy and describe the impact of this strategy on both the NAIIS and the Surge initiatives. METHODS: The NAIIS collaborated with community-based organizations (CBOs) and deployed mobile health (mHealth) technology with real-time dashboards to manage and optimize community LTC for people living with HIV (PLHIV) diagnosed during the survey. In NAIIS, CBOs' role was to facilitate linkage of identified PLHIV in community to facility of their choice. For the ART Surge, we modified the NAIIS LTC strategy by empowering both CBOs and mobile community teams as responsible for not only active LTC but also for community testing, ART initiation, and retention in care. RESULTS: Of the 2,739 PLHIV 15 years and above identified in NAIIS, 1,975 (72.1%) were either unaware of their HIV-positive status (N = 1890) or were aware of their HIV-positive status but not receiving treatment (N = 85). Of these, 1,342 (67.9%) were linked to care, of which 952 (70.9%) were initiated on ART. Among 1,890 newly diagnosed PLHIV, 1,278 (67.6%) were linked to care, 33.7% self-linked and 66.3% were linked by CBOs. Among 85 known PLHIV not on treatment, 64 (75.3%) were linked; 32.8% self-linked and 67.2% were linked by a CBO. In the ART Surge, LTC and treatment initiation rates were 98% and 100%, respectively. Three-month retention for monthly treatment initiation cohorts improved from 76% to 90% over 6 months. CONCLUSIONS: Active LTC strategies by local CBOs and mobile community teams improved LTC and ART initiation in the ART Surge initiative. The use of mHealth technology resulted in timely and accurate documentation of results in NAIIS. By deploying mHealth in addition to active LTC, CBOs and mobile community teams could effectively scale up ART with real-time documentation of client-level outcomes.

Derivation and external validation of a risk score for predicting HIV-associated tuberculosis to support case finding and preventive therapy scale-up: A cohort study.

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) <18.5kg/m2 (2 points), and severe anemia (hemoglobin <8g/dL) (3 points). Sensitivity using WHO 4-symptom TB screen was 73%, 80%, 94%, and 94% in XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively, but increased to 88%, 87%, 97%, and 97%, when a clinical score of ≥2 was used. Negative predictive value (NPV) also increased 1%, 0.3%, 1.6%, and 1.7% in XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively, when the clinical score of ≥2 replaced WHO 4-symptom TB screen. Categorizing risk scores into low (<2), moderate (2 to 10), and high-risk categories (>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.

Ensuring Optimal Community HIV Testing Services in Nigeria Using an Enhanced Community Case-Finding Package (ECCP), October 2019-March 2020: Acceleration to HIV Epidemic Control.

PURPOSE: The 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) showed Nigeria's progress toward the UNAIDS 90-90-90 targets: 47% of HIV-positive individuals knew their status; of these, 96% were receiving antiretroviral therapy (ART); and of these, 81% were virally suppressed. To improve identification of HIV-positive individuals, Nigeria developed an Enhanced Community Case-Finding Package (ECCP). We describe ECCP implementation in nine states and assess its effect. METHODS: ECCP included four core strategies (small area estimation [SAE] of people living with HIV [PLHIV], map of HIV-positive patients by residence, HIV risk-screening tool [HRST], and index testing [IT]) and four supportive strategies (alternative healthcare outlets, performance-based incentives for field testers, Project Extension for Community Healthcare Outcomes, and interactive dashboards). ECCP was deployed in nine of 10 states prioritized for ART scale-up. Weekly program data (October 2019-March 2020) were tracked and analyzed. RESULTS: Of the total 774 LGAs in Nigeria, using SAE, 103 (13.3%) high-burden LGAs were identified, in which 2605 (28.0%) out of 9,294 hotspots were prioritized by mapping newly identified PLHIV by residential addresses. Over 22 weeks, among 882,449 individuals screened using HRST, 723,993 (82.0%) were eligible and tested for HIV (state range, 43.7-90.4%), out of which 20,616 were positive. Through IT, an additional 3,724 PLHIV were identified. In total, 24,340 PLHIV were identified and 97.4% were linked to life-saving antiretroviral therapy. The number of newly identified PLHIV increased 17-fold over 22 weeks (week 1: 89; week 22: 1,632). Overall mean HIV positivity rate by state was 3.3% (range, 1.8-6.4%). CONCLUSION: Using ECCP in nine states in Nigeria increased the number of PLHIV in the community who knew their status, allowing them to access life-saving care and decreasing the risk of HIV transmission.

Scale-up of antiretroviral treatment access among people living with HIV in Rivers State, Nigeria, 2019--2020.

OBJECTIVE: The aim of this study was to describe and evaluate the impact of the programme intervention of the Rivers State Antiretroviral Treatment (ART) Surge, a collaboration between the US President's Emergency Plan for AIDS Relief (PEPFAR) and the State Ministry of Health, to increase HIV case-finding and ART access in Rivers State, the state with the largest ART gap among people living with HIV (PWH) in Nigeria. DESIGN: During April 2019-September 2020, the intervention included six specific strategies: using local government area-level ART gap analysis to guide case-finding; expanding targeted community testing; tailoring comprehensive key population HIV services; engaging HIV treatment programme stakeholders; synchronizing team efforts; and using near real-time data for programme action. METHODS: Weekly reported facility and community data on tests conducted, PWH diagnosed, and PWH initiated on ART were aggregated. The total number of PWH maintained on ART was reported quarterly. RESULTS: During May 2019-September 2020, the weekly number of newly diagnosed PWH initiated on ART supported by PEPFAR in Rivers State increased from 82 to 1723. During October 2019-September 2020, the monthly number of people screened for HIV testing eligibility in the community increased from 44 000 to 360 000. During April 2019-September 2020, the total number of PWH on ART supported by PEPFAR statewide increased by 3.8 times, from 26 041 to 99 733. CONCLUSION: The strategies applied by HIV program stakeholders contributed to scale-up of PWH identification and ART linkage within the Rivers State ART Surge. Continued gains through time indicate the importance of the application of a quality improvement approach to maintain programme flexibility and effectiveness.

Rapid Scale-up of an Antiretroviral Therapy Program Before and During the COVID-19 Pandemic - Nine States, Nigeria, March 31, 2019-September 30, 2020.

In 2018, an estimated 1.8 million persons living in Nigeria had HIV infection (1.3% of the total population), including 1.1 million (64%) who were receiving antiretroviral therapy (ART) (1). Effective ART reduces morbidity and mortality rates among persons with HIV infection and prevents HIV transmission once viral load is suppressed to undetectable levels (2,3). In April 2019, through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR),* CDC launched an 18-month ART Surge program in nine Nigerian states to rapidly increase the number of persons with HIV infection receiving ART. CDC analyzed programmatic data gathered during March 31, 2019-September 30, 2020, to describe the ART Surge program's progress on case finding, ART initiation, patient retention, and ART Surge program growth. Overall, the weekly number of newly identified persons with HIV infection who initiated ART increased approximately eightfold, from 587 (week ending May 4, 2019) to 5,329 (week ending September 26, 2020). The ART Surge program resulted in 208,202 more HIV-infected persons receiving PEPFAR-supported ART despite the COVID-19 pandemic (97,387 more persons during March 31, 2019-March 31, 2020 and an additional 110,815 persons during April 2020-September 2020). Comprehensive, data-guided, locally adapted interventions and the use of incident command structures can help increase the number of persons with HIV infection who receive ART, reducing HIV-related morbidity and mortality as well as decreasing HIV transmission.

Risk scores for predicting early antiretroviral therapy mortality in sub-Saharan Africa to inform who needs intensification of care: a derivation and external validation cohort study.

BACKGROUND: Clinical 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 < 200/µL or WHO stage III/IV. METHODS: We 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. RESULTS: Among 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 at p < 0.01 and selected for the CD4-independent score included male gender (2 points), ≥ 1 WHO tuberculosis symptom (2 points), WHO stage III/IV (2 points), severe anemia (hemoglobin < 8 g/dL) (3 points), and temperature > 37.5 °C (2 points). The same variables plus CD4 < 200/µL (1 point) were included in the CD4-dependent score. Among XPRES enrollees, a CD4-independent score of ≥ 4 would provide 86% sensitivity and 66% specificity, whereas WHO EC would provide 83% sensitivity and 58% specificity. If WHO stage alone was used, sensitivity was 48% and specificity 89%. Among TBFT enrollees, the CD4-independent score of ≥ 4 would provide 95% sensitivity and 27% specificity, whereas WHO EC would provide 100% sensitivity but 0% specificity. Accuracy was similar between CD4-independent and CD4-dependent scores. Categorizing CD4-independent scores into low (< 4), moderate (4-6), and high risk (≥ 7) gave 6-month mortality of 1%, 4%, and 17% for XPRES and 1%, 5%, and 30% for TBFT enrollees. CONCLUSIONS: Sensitivity 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.

Implementation and evaluation of a Project ECHO telementoring program for the Namibian HIV workforce.

BACKGROUND: The Namibian Ministry of Health and Social Services (MoHSS) piloted the first HIV Project ECHO (Extension for Community Health Outcomes) in Africa at 10 clinical sites between 2015 and 2016. Goals of Project ECHO implementation included strengthening clinical capacity, improving professional satisfaction, and reducing isolation while addressing HIV service challenges during decentralization of antiretroviral therapy. METHODS: MoHSS conducted a mixed-methods evaluation to assess the pilot. Methods included pre/post program assessments of healthcare worker knowledge, self-efficacy, and professional satisfaction; assessment of continuing professional development (CPD) credit acquisition; and focus group discussions and in-depth interviews. Analysis compared the differences between pre/post scores descriptively. Qualitative transcripts were analyzed to extract themes and representative quotes. RESULTS: Knowledge of clinical HIV improved 17.8% overall (95% confidence interval 12.2-23.5%) and 22.3% (95% confidence interval 13.2-31.5%) for nurses. Professional satisfaction increased 30 percentage points. Most participants experienced reduced professional isolation (66%) and improved CPD credit access (57%). Qualitative findings reinforced quantitative results. Following the pilot, the Namibia MoHSS Project ECHO expanded to over 40 clinical sites by May 2019 serving more than 140 000 people living with HIV. CONCLUSIONS: Similar to other Project ECHO evaluation results in the United States of America, Namibia's Project ECHO led to the development of ongoing virtual communities of practice. The evaluation demonstrated the ability of the Namibia HIV Project ECHO to improve healthcare worker knowledge and satisfaction and decrease professional isolation.

Increase in Antiretroviral Therapy Enrollment Among Persons with HIV Infection During the Lusaka HIV Treatment Surge - Lusaka Province, Zambia, January 2018-June 2019.

Within Zambia, a landlocked country in southern-central Africa, the highest prevalence of human immunodeficiency virus (HIV) infection is in Lusaka Province (population 3.2 million), where approximately 340,000 persons are estimated to be infected (1). The 2016 Zambia Population-based HIV Impact Assessment (ZAMPHIA) estimated the adult HIV prevalence in Lusaka Province to be 15.7%, with a 62.7% viral load suppression rate (HIV-1 RNA <1,000 copies/mL) (2). ZAMPHIA results highlighted remaining treatment gaps in Zambia overall and by subpopulation. In January 2018, Zambia launched the Lusaka Province HIV Treatment Surge (Surge project) to increase enrollment of persons with HIV infection onto antiretroviral therapy (ART). The Zambia Ministry of Health (MoH), CDC, and partners analyzed the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) Monitoring and Evaluation Reporting data set to assess the effectiveness of the first 18 months of the Surge project (January 2018-June 2019). During this period, approximately 100,000 persons with positive test results for HIV began ART. These new ART clients were more likely to be persons aged 15-24 years. In addition, the number of persons with documented viral load suppression doubled from 66,109 to 134,046. Lessons learned from the Surge project, including collaborative leadership, efforts to improve facility-level performance, and innovative strategies to disseminate successful practices, could increase HIV treatment rates in other high-prevalence settings.

Effect of tuberculosis screening and retention interventions on early antiretroviral therapy mortality in Botswana: a stepped-wedge cluster randomized trial.

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).

Implementation of the Treat All Policy Among Persons with HIV Infection Enrolled in Care But Not on Antiretroviral Therapy - India, May 2017-June 2018.

Since September 2015, the World Health Organization has recommended antiretroviral therapy (ART) for all persons with human immunodeficiency virus (HIV) infection, regardless of clinical stage or CD4 count (1). This Treat All policy was based on evidence that ART initiation early in HIV infection as opposed to waiting for the CD4 count to decline to certain levels (e.g., <500 cells/mm3, per previous guidelines), was associated with reduced morbidity, mortality, and HIV transmission (2-4). Further, approximately half of persons enrolled in non-ART care that included monitoring for HIV disease progression (i.e., in pre-ART care) were lost to follow-up before becoming ART-eligible (5). India, the country with the third largest number of persons with HIV infection in the world (2.1 million), adopted the Treat All policy on April 28, 2017. This report describes implementation of Treat All during May 2017-June 2018, by India's National AIDS Control Organization (NACO) and partners, by facilitating ART initiation among persons previously in pre-ART care at 46 ART centers supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR)* in six districts in the states of Maharashtra and Andhra Pradesh. Partners supported these 46 ART centers in identifying and attempting to contact persons who were enrolled in pre-ART care during January 2014-April 2017, and educating those reached about Treat All. ART center-based records were used to monitor implementation indicators, including ART initiation. A total of 9,898 (39.6%) of 25,007 persons previously enrolled in pre-ART care initiated ART; among these 9,898 persons, 6,315 (63.8%) initiated ART after being reached during May 2017-June 2018, including 1,635 (16.5%) who had been lost to follow-up before ART initiation. NACO scaled up efforts nationwide to build ART centers' capacity to implement Treat All. Active tracking and tracing of persons with HIV infection enrolled in care but not on ART, combined with education about the benefits of early HIV treatment, can facilitate ART initiation.

High rates of loss to follow-up during the first year of pre-antiretroviral therapy for HIV patients at sites providing pre-ART care in Nigeria, 2004-2012.

BACKGROUND: With about 3.4 million HIV-infected persons, Nigeria has the second highest number of people living with HIV (PLHIV) in the world. However, antiretroviral treatment (ART) coverage in Nigeria remains low with only 748,846 (22%) of PLHIV on ART by the end of 2014. Retention of HIV-infected patients in pre-ART care is essential to ensure timely ART initiation. We assessed outcomes of patients enrolled in Nigeria's pre-ART program during 2004-2012. METHODS: We conducted a nationally representative retrospective cohort study among adults (≥15 years old), enrolling in pre-ART programs supported by the U.S. President's Emergency Plan for AIDS Relief in Nigeria. A total of 35 sites enrolling ≥50 patients in pre-ART were selected using probability proportional-to-size sampling; 2,415 eligible medical records at these sites were randomly selected for abstraction. Determinants of loss to follow-up (LTFU) and mortality during pre-ART care were estimated using Cox proportional hazards regression models. RESULTS: The median age at enrollment was 32 years (interquartile range (IQR) 27-40). A total of 1,216 (51.4%) initiated ART by the time of data abstraction. Among the remaining 1,199 patients, 898 (74.9%) had been LTFU, 180 (15.0%) were alive and in pre-ART care, 71 (5.9%) had died, 50 (4.2%) had transferred out or stopped care. Baseline markers of advanced disease, including weight <45 kg (adjusted hazard ration (AHR) = 4.23; 95% confidence interval (CI): 1.51-15.58) and more advanced WHO disease stage, were predictive of pre-ART mortality. Compared with patients aged 15-24, patients aged 35-44 (AHR = 0.67; 95% CI: 1.0.47-0.95) and age 45-54 (AHR = 0.66; 95% CI: 0.48-0.91) had lower LTFU rates. Compared with attending facilities in North Central geopolitical zone, attending facility locations in South East (AHR = 0.44; 95% CI: 0.24-0.83) was protective against LTFU. CONCLUSIONS: About half of patients enrolling in HIV program during 2004-2012 in Nigeria had not initiated ART by 2013. Key strategies to improve early ART initiation among pre-ART enrollees include implementation of the WHO test and treat guidelines, earlier HIV testing, and better monitoring to improve ART initiation rates. Further research to understand regional variations in pre-ART outcomes is warranted.

Incidence and predictors of tuberculosis among HIV-infected adults after initiation of antiretroviral therapy in Nigeria, 2004-2012.

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<50/µL (adjusted hazard ratio [AHR]: 4.2, 95% confidence interval [CI]: 1.4-12.7) compared with CD4≥200/µL. Patients with suspected but untreated TB at ART initiation and those with a history of prior TB were more likely to develop incident TB (AHR: 12.2, 95% CI: 4.5-33.5 and AHR: 17.6, 95% CI: 3.5-87.9, respectively). CONCLUSION: Incidence of TB among PLHIV after ART initiation was low, and predicted by advanced HIV, prior TB, and suspected but untreated TB. Study results suggest a need for improved TB screening and diagnosis, particularly among high-risk PLHIV initiating ART, and reinforce the benefit of early ART and other TB prevention efforts.

Correction: Outcomes of Nigeria's HIV/AIDS Treatment Program for Patients Initiated on Antiretroviral Treatment between 2004-2012.

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

Outcomes of Nigeria's HIV/AIDS Treatment Program for Patients Initiated on Antiretroviral Treatment between 2004-2012.

BACKGROUND: The Nigerian Antiretroviral therapy (ART) program started in 2004 and now ranks among the largest in Africa. However, nationally representative data on outcomes have not been reported. METHODS: We evaluated retrospective cohort data from a nationally representative sample of adults aged ≥15 years who initiated ART during 2004 to 2012. Data were abstracted from 3,496 patient records at 35 sites selected using probability-proportional-to-size (PPS) sampling. Analyses were weighted and controlled for the complex survey design. The main outcome measures were mortality, loss to follow-up (LTFU), and retention (the proportion alive and on ART). Potential predictors of attrition were assessed using competing risk regression models. RESULTS: At ART initiation, 66.4 percent (%) were females, median age was 33 years, median weight 56 kg, median CD4 count 161 cells/mm3, and 47.1% had stage III/IV disease. The percentage of patients retained at 12, 24, 36 and 48 months was 81.2%, 74.4%, 67.2%, and 61.7%, respectively. Over 10,088 person-years of ART, mortality, LTFU, and overall attrition (mortality, LTFU, and treatment stop) rates were 1.1 (95% confidence interval (CI): 0.7-1.8), 12.3 (95%CI: 8.9-17.0), and 13.9 (95% CI: 10.4-18.5) per 100 person-years (py) respectively. Highest attrition rates of 55.4/100py were witnessed in the first 3 months on ART. Predictors of LTFU included: lower-than-secondary level education (reference: Tertiary), care in North-East and South-South regions (reference: North-Central), presence of moderate/severe anemia, symptomatic functional status, and baseline weight <45kg. Predictor of mortality was WHO stage higher than stage I. Male sex, severe anemia, and care in a small clinic were associated with both mortality and LTFU. CONCLUSION: Moderate/Advanced HIV disease was predictive of attrition; earlier ART initiation could improve program outcomes. Retention interventions targeting men and those with lower levels of education are needed. Further research to understand geographic and clinic size variations with outcome is warranted.

Implementation of a pragmatic, stepped-wedge cluster randomized trial to evaluate impact of Botswana's Xpert MTB/RIF diagnostic algorithm on TB diagnostic sensitivity and early antiretroviral therapy mortality.

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 .