Use of a Handheld Ultrasonographic Device to Identify Heart Failure and Pulmonary Disease in Rural Africa.

Importance: Agreement in lung ultrasonography findings between clinicians using a handheld ultrasonographic device and expert sonographers using a high-end ultrasonographic machine has not been studied in sub-Saharan Africa. Objective: To determine the agreement in ultrasonographic findings and diagnoses between primary care clinicians trained in lung ultrasonography, board-certified expert sonographers, and senior physicians. Design, Setting, and Participants: This cross-sectional single-center study was conducted from February 1, 2022, to April 30, 2023 at a referral center in rural Tanzania. Individuals 5 years or older with respiratory symptoms and at least 2 distinct respiratory signs or symptoms were eligible. A total of 459 individuals were screened. Exposures: Participants provided their medical history and underwent a clinical examination and lung ultrasonography performed by a clinician, followed by a lung ultrasonography performed by an expert sonographer, and finally chest radiography and a final evaluation performed by a senior physician. Other tests, such as echocardiography and Mycobacterium tuberculosis testing, were conducted on the decision of the physician. Clinicians received 2 hours of instruction and three 2-hour sessions of clinical training in the use of a handheld lung ultrasonographic device; expert sonographers were board-certified. Main Outcomes and Measures: Percentage agreement and Cohen κ coefficient for sonographic findings and diagnoses compared between clinicians and expert sonographers, and between clinicians and senior physicians. Results: The median (IQR) age of 438 included participants was 54 (38-66) years, and 225 (51%) were male. The median (range) percentage agreement of ultrasonographic findings between clinicians and expert sonographers was 93% (71%-99%), with κ ranging from -0.003 to 0.83. Median (range) agreement of diagnoses between clinicians and expert sonographers was 90% (50%-99%), with κ ranging from -0.002 to 0.76. Between clinicians and senior physicians, median (range) agreement of diagnoses was 89% (55%-90%), with κ ranging from -0.008 to 0.76. Between clinicians and senior physicians, diagnosis agreements were 85% (κ, 0.69) for heart failure, 78% (κ, 0.57) for definite or probable tuberculosis, 50% (κ, 0.002) for viral pneumonia, and 56% (κ, 0.06) for bacterial pneumonia. Conclusions and Relevance: In this cross-sectional study, the agreement of ultrasonographic findings between clinicians and sonographers was mostly substantial. Between clinicians and senior physicians, agreement was substantial in the diagnosis of heart failure, moderate in the diagnosis of tuberculosis, but slight in the diagnosis of pneumonia. These findings suggest that handheld ultrasonographic devices used in addition to clinical examination may support clinicians in diagnosing cardiac and pulmonary diseases in rural sub-Saharan Africa.

Improving anaemia diagnosis using peripheral blood smear with remote interpretation in adults living with HIV with moderate to severe anaemia: A prospective study nested within the Kilombero and Ulanga antiretroviral cohort.

INTRODUCTION: In low-resource settings, anaemia is a very common condition. Identification of anaemia aetiologies remains challenging due to the lack of diagnostic tools and expertise. We aimed to improve anaemia diagnostics using peripheral blood smear (PBS) with remote interpretation in people living with HIV (PLHIV) with moderate to severe anaemia. METHODS: We conducted a prospective study nested within the Kilombero and Ulanga Antiretroviral Cohort, including non-pregnant PLHIV aged ≥18 years presenting with moderate (haemoglobin 7.0-9.9 g/dl) or severe (<7.0 g/dl) anaemia at any visit from January 2019 to December 2020. For each participant, ten PBS images, full blood count and clinical details were shared with a haematologist for remote interpretation (enhanced care). Identification of anaemia etiologies and potential impact on treatment was compared between enhanced and standard care. RESULTS: Among 400 PLHIV with moderate to severe anaemia, 349 (87%) were female, median age was 40 years (interquartile range (IQR) 35-46)), 65 (17%) had a body mass index <18.5 kg/m2, 215 (54%) had HIV WHO stage III/IV, 79 (20%) had a CD4 cell count <200 cells/µl and 317 (89%) had HIV viral load <100 copies/ml. Severe anaemia was diagnosed in 84 (21%). Suspected multiple aetiologies were documented more frequently by enhanced care compared to standard care 267 (67%) vs 20 (5%); p<0.001. Suspected iron deficiency was the most frequent aetiology (n = 337; 84%), followed by chronic disease (n = 199; 50%), folate/vitamin B12 deficiency (n = 78; 20%) and haemoglobinopathy (n = 83; 21%). In 272 participants (68%), enhanced care revealed additional clinically relevant findings with impact on the treatment recommendation. CONCLUSION: Remote interpretation of PBS combined with clinical information and blood cell count results can provide insights to the suspected aetiological diagnosis of moderate and severe anaemia in rural low-resource settings and impact specific treatment.

Transitioning to Dolutegravir in a Programmatic Setting: Virological Outcomes and Associated Factors Among Treatment-Naive Patients With HIV-1 in the Kilombero and Ulanga Antiretroviral Cohort in Rural Tanzania.

Background: Virological outcome data after programmatic transition from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based to dolutegravir (DTG)-based antiretroviral therapy (ART) regimens in sub-Saharan Africa (SSA) outside of clinical trials are scarce. We compared viral suppression and associated factors in treatment-naïve people living with HIV (PLHIV) starting DTG- based versus NNRTI-based ART. Methods: We compared virological suppression at 12 months, after treatment initiation in the two cohorts of participants aged ≥15 years, initiating DTG- and NNRTI-based ART. Drug resistance was assessed among participants with viremia ≥50 copies/mL on DTG. Results: Viral suppression was achieved for 165/195 (85%) and 154/211 (73%) participants in the DTG- and NNRTI- cohorts, respectively (P = 0.003). DTG-based ART was associated with >2 times the odds of viral suppression versus NNRTI-based ART (adjusted odds ratio, 2.10 [95% confidence interval {CI}, 1.12-3.94]; adjusted risk ratio, 1.11 [95% CI, 1.00-1.24]). HIV-1 genotypic resistance testing (GRT) before ART initiation was done in 14 of 30 viremic participants on DTG, among whom nucleoside reverse transcriptase inhibitor (NRTI), NNRTI, and protease inhibitors resistance was detected in 0 (0%), 2 (14%) and 1 (7%), respectively. No resistance was found in the 2 of 30 participants with available GRT at the time of viremia ≥50 copies/mL. Conclusions: Virological suppression at 1 year was higher in participants initiating DTG- versus NNRTI-based ART. In those with viremia ≥50 copies/mL on DTG-based ART, there was no pretreatment or acquired resistance to the DTG co-administered NRTIs, although the number of samples tested was small.

Prevalence of fever of unidentified aetiology in East African adolescents and adults: a systematic review and meta-analysis.

BACKGROUND: Primary health care settings and hospitals of low- and middle-income countries have few accessible diagnostic tools and limited laboratory and human resources capacity to identify multiple pathogens with high accuracy. In addition, there is a paucity of information on fever and its underlying aetiology in the adolescent and adult population in East Africa. The purpose of this study was to estimate the pooled prevalence of fever of unidentified aetiology among adolescent and adult febrile patients seeking health care in East Africa. METHODS: We pursued a systematic review using readily available electronic databases (i.e. PubMed, Cumulative Index to Nursing & Allied Health Literature, Scopus, Cochrane Library and Web of Science) without language restriction from inception date of the respective databases to October 31, 2022. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Identified studies were screened for relevance. Further analyses based on pre-set eligibility criteria were carried out for final inclusion. Two reviewers independently screened and extracted data. Risk of study bias was assessed. Meta-analysis of the prevalence of fever of unidentified aetiology was performed. RESULTS: We identified 14,029 articles of which 25 were eligible for inclusion, reporting data from 8538 participants. The pooled prevalence of febrile cases with unidentified aetiology was 64% [95% confidence interval (CI): 51-77%, I2 = 99.6%] among febrile adolescents and adults in East Africa. For the proportion of patients with identified aetiology, the studies documented bacterial pathogens (human bloodstream infections), bacterial zoonotic pathogens and arboviruses as the main non-malarial causative agents in East Africa. CONCLUSIONS: Our study provides evidence that almost two-thirds of adolescent and adult febrile patients attending health care facilities in East Africa might receive inappropriate treatments due to unidentified potential life-threatening fever aetiology. Hence, we call for a comprehensive fever syndromic surveillance to broaden a consequential differential diagnosis of syndromic fever and to considerably improve the course of patients' disease and treatment outcomes.

Decentralization of viral load testing to improve HIV care and treatment cascade in rural Tanzania: observational study from the Kilombero and Ulanga Antiretroviral Cohort.

INTRODUCTION: Monitoring HIV viral load (HVL) in people living with HIV (PLHIV) on antiretroviral therapy (ART) is recommended by the World Health Organization. Implementation of HVL testing programs have been affected by logistic and organizational challenges. Here we describe the HVL monitoring cascade in a rural setting in Tanzania and compare turnaround times (TAT) between an on-site and a referral laboratory. METHODS: In a nested study of the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) we included PLHIV aged ≥ 15 years, on ART for ≥ 6 months after implementation of routine HVL monitoring in 2017. We assessed proportions of PLHIV with a blood sample taken for HVL, whose results came back, and who were virally suppressed (HVL < 1000 copies/mL) or unsuppressed (HVL ≥ 1000 copies/mL). We described the proportion of PLHIV with unsuppressed HVL and adequate measures taken as per national guidelines and outcomes among those with low-level viremia (LLV; 100-999 copies/mL). We compare TAT between on-site and referral laboratories by Wilcoxon rank sum tests. RESULTS: From 2017 to 2020, among 4,454 PLHIV, 4,238 (95%) had a blood sample taken and 4,177 (99%) of those had a result. Of those, 3,683 (88%) were virally suppressed. In the 494 (12%) unsuppressed PLHIV, 425 (86%) had a follow-up HVL (102 (24%) within 4 months and 158 (37%) had virologic failure. Of these, 103 (65%) were already on second-line ART and 32/55 (58%) switched from first- to second-line ART after a median of 7.7 months (IQR 4.7-12.7). In the 371 (9%) PLHIV with LLV, 327 (88%) had a follow-up HVL. Of these, 267 (82%) resuppressed to < 100 copies/ml, 41 (13%) had persistent LLV and 19 (6%) had unsuppressed HVL. The median TAT for return of HVL results was 21 days (IQR 13-39) at the on-site versus 59 days (IQR 27-99) at the referral laboratory (p < 0.001) with PLHIV receiving the HVL results after a median of 91 days (IQR 36-94; similar for both laboratories). CONCLUSION: Robust HVL monitoring is achievable in remote resource-limited settings. More focus is needed on care models for PLHIV with high viral loads to timely address results from routine HVL monitoring.

Correction: Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.

[This corrects the article DOI: 10.1371/journal.pmed.1004189.].

Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.

BACKGROUND: For a full treatment course of severe malaria, community-administered pre-referral rectal artesunate (RAS) should be completed by post-referral treatment consisting of an injectable antimalarial and oral artemisinin-based combination therapy (ACT). This study aimed to assess compliance with this treatment recommendation in children under 5 years. METHODS AND FINDINGS: This observational study accompanied the implementation of RAS in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Antimalarial treatment was assessed during admission in included referral health facilities (RHFs) in children under 5 with a diagnosis of severe malaria. Children were either referred from a community-based provider or directly attending the RHF. RHF data of 7,983 children was analysed for appropriateness of antimalarials; a subsample of 3,449 children was assessed additionally for dosage and method of ACT provision (treatment compliance). A parenteral antimalarial and an ACT were administered to 2.7% (28/1,051) of admitted children in Nigeria, 44.5% (1,211/2,724) in Uganda, and 50.3% (2,117/4,208) in DRC. Children receiving RAS from a community-based provider were more likely to be administered post-referral medication according to the guidelines in DRC (adjusted odds ratio (aOR) = 2.13, 95% CI 1.55 to 2.92, P < 0.001), but less likely in Uganda (aOR = 0.37, 95% CI 0.14 to 0.96, P = 0.04) adjusting for patient, provider, caregiver, and other contextual factors. While in DRC, inpatient ACT administration was common, ACTs were often prescribed at discharge in Nigeria (54.4%, 229/421) and Uganda (53.0%, 715/1,349). Study limitations include the unfeasibility to independently confirm the diagnosis of severe malaria due to the observational nature of the study. CONCLUSIONS: Directly observed treatment was often incomplete, bearing a high risk for partial parasite clearance and disease recrudescence. Parenteral artesunate not followed up with oral ACT constitutes an artemisinin monotherapy and may favour the selection of resistant parasites. In connection with the finding that pre-referral RAS had no beneficial effect on child survival in the 3 study countries, concerns about an effective continuum of care for children with severe malaria seem justified. Stricter compliance with the WHO severe malaria treatment guidelines is critical to effectively manage this disease and further reduce child mortality. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03568344).

Stigma-directed services (Stig2Health) to improve 'linkage to care' for people living with HIV in rural Tanzania: study protocol for a nested pre-post implementation study within the Kilombero and Ulanga Antiretroviral Cohort.

Background: HIV-related stigma is a major barrier to the timely linkage and retention of patients in HIV care in sub-Saharan Africa, where most people living with HIV/AIDS reside. In this implementation study we aim to evaluate the effect of stigma-directed services on linkage to care and other health outcomes in newly diagnosed HIV-positive patients. Methods: In a nested project of the Kilombero and Ulanga Antiretroviral Cohort in rural Tanzania, we conduct a prospective observational pre-post study to assess the impact of a bundle of stigma-directed services for newly diagnosed HIV positive patients. Stigma-directed services, delivered by a lay person living with HIV, are i) post-test counseling, ii) post-test video-assisted teaching, iii) group support therapy and group health education, and iv) mobile health. Patients receiving stigma services (enrolled from 1 st February 2020 to 31 st August 2021) are compared to a historical control receiving the standard of care (enrolled from 1 st July 2017 to 1 st February 2019). The primary outcome is 'linkage to care'. Secondary endpoints are retention in care, viral suppression, death and clinical failure at 6-12 months (up to 31 st August 2022). Self-reported stigma and depression are assessed using the Berger Stigma scale and the PHQ-9 questionnaire, respectively. The sample size calculation was based on cohort data from 2018. Assuming a pre-intervention cohort of 511 newly diagnosed adults of whom 346 (68%) were in care and on antiretroviral treatment (ART) at 2 months, a 10% increase in linkage (from 70 to 80%), a two-sided type I error rate of 5%, and 90% power, 321 adults are required for the post-implementation group. Discussion: We expect that integration of stigma-directed services leads to an increase of proportions of patients in care and on ART. The findings will provide guidance on how to integrate stigma-directed services into routine care in rural sub-Saharan Africa.

Failure to return pillbox is a predictor of being lost to follow-up among people living with HIV on antiretroviral therapy in rural Tanzania.

OBJECTIVES: Pill count is used to assess drug adherence in people living with HIV (PLHIV). Carrying a pillbox is associated with fear of concealment and stigma and might indicate poor adherence and predict someone who will be lost to follow-up (LTFU). We therefore assessed the association between pillbox return and being LTFU in rural Tanzania. METHODS: This is a nested study of the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). We included PLHIV aged ≥ 18 years enrolled in KIULARCO between January 2013 and March 2019 with follow-up through January 2020, who were on antiretroviral treatment (ART) for ≥ 6 months. Baseline was defined as the latest ART initiation or KIULARCO enrolment. We determined the association between time-dependent failed pillbox return updated at every visit and LTFU using Kaplan-Meier estimation and Cox models. RESULTS: Among 2552 PLHIV included in the study, 1735 (68.0%) were female, 959 (40.3%) had a WHO stage III/IV and 1487 (66.4%) had a CD4 cell count < 350 cells/µL. The median age was 38.4 years [interquartile range (IQR): 31.7-46.2]. During a median follow-up of 33.1 months (IQR: 17.5-52.4), 909 (35.6%) participants were LTFU, 43 (1.7%) died and 194 (7.6%) had transferred to another clinic. The probability of being LTFU was higher among PLHIV with failed pillbox return than among those who returned their pillbox [30.0%, 95% confidence interval (CI): 26.8-33.2% vs. 19.4%, 95% CI: 17.4-21.6%, respectively, at 24 months (hazard ratio = 1.67, 95% CI: 1.46-1.90; p < 0.001)]. CONCLUSIONS: Failed pillbox return was associated with a higher risk of being LTFU and could be used as a simple tool to identify PLHIV for appropriate interventions to reduce their chance of being LTFU.

Prevalence, incidence and predictors of renal impairment in persons with HIV receiving protease-inhibitors in rural Tanzania.

OBJECTIVE: Ritonavir-boosted protease inhibitors (bPI) in people living with HIV (PLWH) have been associated with renal impairment. Limited data are available from rural sub-Saharan Africa. METHODS: Using data from the Kilombero and Ulanga Antiretroviral Cohort Study (KIULARCO) in rural Tanzania from 2005-01/2020, we assessed the prevalence of renal impairment (estimated glomerular filtration rate <60 mL/min/1.73m2) at the time of switch from first-line antiretroviral treatment (ART) to bPI-regimen and the incidence of renal impairment on bPI. We assessed risk factors for renal impairment using logistic and Cox regression models. RESULTS: Renal impairment was present in 52/687 PLWH (7.6%) at the switch to bPI. Among 556 participants with normal kidney function at switch, 41 (7.4%) developed renal impairment after a median time of 3.5 (IQR 1.6-5.1) years (incidence 22/1,000 person-years (95%CI 16.1-29.8)). Factors associated with renal impairment at switch were older age (adjusted odds ratio (aOR) 1.55 per 10 years; 95%CI 1.15-2.11), body mass index (BMI) <18.5 kg/m2 (aOR 2.80 versus ≥18kg/m2; 95%CI 1.28-6.14) and arterial hypertension (aOR 2.33; 95%CI 1.03-5.28). The risk of renal impairment was lower with increased duration of ART use (aOR 0.78 per one-year increase; 95%CI 0.67-0.91). The renal impairment incidence under bPI was associated with older age (adjusted hazard ratio 2.01 per 10 years; 95%CI 1.46-2.78). CONCLUSIONS: In PLWH in rural sub-Saharan Africa, prevalence and incidence of renal impairment among those who were switched from first-line to bPI-regimens were high. We found associations between renal impairment and older age, arterial hypertension, low BMI and time on ART.

High burden of tuberculosis infection and disease among people receiving medication-assisted treatment for substance use disorder in Tanzania.

OBJECTIVE: To determine the prevalence of tuberculosis (TB) disease and infection as well as incident TB disease among people who use drugs (PWUD) attending Medication Assisted Treatment (MAT) clinics in Dar-es-Salaam, Tanzania. METHODS: In this prospective cohort study, a total of 901 consenting participants were enrolled from November 2016 to February 2017 and a structured questionnaire administered to them through the open data kit application on android tablets. Twenty-two months later, we revisited the MAT clinics and reviewed 823 of the 901 enrolled participant's medical records in search for documentation on TB disease diagnosis and treatment. Medical records reviewed included those of participants whom at enrolment were asymptomatic, not on TB disease treatment, not on TB preventive therapy and those who had a documented tuberculin skin test (TST) result. RESULTS: Of the 823 medical records reviewed 22 months after enrolment, 42 had documentation of being diagnosed with TB disease and initiated on TB treatment. This is equivalent to a TB disease incidence rate of 2,925.2 patients per 100,000 person years with a total follow up time of 1,440 person-years. At enrolment the prevalence of TB disease and TB infection was 2.6% and 54% respectively and the HIV prevalence was 44% and 16% among females and males respectively. CONCLUSION: PWUD attending MAT clinics bear an extremely high burden of TB and HIV and are known to have driven TB epidemics in a number of countries. Our reported TB disease incidence is 12 times that of the general Tanzanian incidence of 237 per 100,000 further emphasizing that this group should be prioritized for TB screening, testing and treatment. Gender specific approaches should also be developed as female PWUDs are markedly more affected with HIV and TB disease than male PWUDs.

Prevalence and risk factors for obesity among elderly patients living with HIV/AIDS in a low-resource setting.

ABSTRACT: Obesity is associated with detrimental changes in cardiovascular and metabolic parameters, including blood pressure, dyslipidemia, markers of systemic inflammation, and insulin resistance. In the elderly living with the human immunodeficiency virus (EPLHIV), and being treated with antiretroviral medications, the obesity complications escalate and expose the elderly to the risk of noncommunicable diseases. Given that over 3 million EPLHIV in sub-Sahara Africa, we assessed the prevalence of obesity and its associated factors among EPLHIV in a low-resource setting.This was a cross sectional study of EPLHIV aged 50 years and older, being treated with antiretroviral medications from 2004 to 2018. HIV treatment data collected from multiple treatment sites were analyzed. Baseline characteristics of the participants were described, and multivariable relative risk model was applied to assess the associations between obesity (body mass index [BMI] ≥30 kg/m2) and the prespecified potential risk factors.Of the 134,652 in HIV cohort, 19,566 (14.5%) were EPLHIV: 12,967 (66.3%) were normal weight (18.5 ≤ BMI < 25), 4548 (23.2%) were overweight (25 ≤ BMI < 30), while 2,051 (10.5%) were obese (BMI ≥30). The average age the normal weight (57.1; standard deviation 6.6) and the obese (56.5; standard deviation 5.5) was similar. We observed that being an employed (relative risk [RR] 1.71; 95% confidence interval [CI] 1.48-2.00; P < .001), educated (RR 1.93; 95% CI 1.54-2.41; P < .001), and presence of hypertension (RR 1.78; 95% CI 1.44-2.20; P < .001), increased the risk of obesity. Also, being male (RR 0.38; 95% CI 0.33-0.44; P < .001), stages III/IV of the World Health Organization clinical stages of HIV (RR 0.58; 95% CI 0.50-0.68; P < .001), tenofovir-based regimen (RR 0.84; 95% CI 0.73-0.96, P < .001), and low CD4 count (RR 0.56; 95% CI 0.44-0.71; P < .001) were inversely associated with obesity.This study demonstrates that multiple factors are driving obesity prevalence in EPLHIV. The study provides vital information for policy-makers and HIV program implementers in implementing targeted-interventions to address obesity in EPLHIV. Its findings would assist in the implementation of a one-stop-shop model for the management of HIV and other comorbid medical conditions in EPLHIV.

Cohort profile: the Nigerian HIV geriatric cohort study.

BACKGROUND: The Nigerian HIV Geriatric Cohort (NHGC) is a longitudinal cohort setup to learn how elderly people living with HIV (EPLHIV) in Nigeria fare, despite not being prioritized by the national treatment program, and to deepen knowledge for their differentiated care and achieve better outcomes. In this paper, we describe data collected on sociodemographic and clinical data from EPLHIV from the inception of Nigeria's national HIV program to 2018. METHODS: Patient-level data spanning the period 2004 to 2018, obtained from comprehensive HIV treatment hospitals, that are supported by four major PEPFAR-implementing partners in Nigeria were used. These 4 entities collaborated as member organizations of the Nigeria Implementation Science Alliance. We defined elderly as those aged 50 years and above. From deidentified treatment records, demographic and clinical data of EPLHIV ≥50-year-old at ART initiation during the review period was extracted, merged into a single REDcap® database, and described using STATA 13. RESULTS: A total of 101,652 EPLHIV were analysed. Women accounted for 53,608 (53%), 51,037 (71%) of EPLHIV identified as married and 33,446 (51%) unemployed. Median age was 57.1 years (IQR 52-60 years) with a median duration on ART treatment of 4.1 years (IQR 1.7-7.1 years). ART profile showed that 97,586 (96%) were on 1st-line and 66,125 (65%) were on TDF-based regimens. Median body mass index (BMI) was 22.2 kg/m2 (IQR 19.5-25.4 kg/m2) with 43,012 (55%), 15,081 (19%) and 6803 (9%) showing normal (BMI 18.5 - < 25 kg/m2), overweight (BMI 25 - < 30 kg/m2) and obese (BMI ≥30 kg/m2) ranges respectively. Prevalence of hypertension (systolic-BP > 140 mmHg or diastolic-BP > 90 mmHg) was 16,201 (21%). EPLHIV median CD4 count was 381 cells/µL (IQR 212-577 cells/µL) and 26,687 (82%) had a viral load result showing < 1000copies/ml within one year of their last visit. As for outcomes at their last visit, 62,821 (62%) were on active-in-treatment, 28,463 (28%) were lost-to-follow-up, 6912 (7%) died and 2456 (3%) had stopped or transferred out. Poor population death records and aversion to autopsies makes it almost impossible to estimate AIDS-related deaths. CONCLUSIONS: This cohort describes the clinical and non-clinical profile of EPLHIV in Nigeria. We are following up the cohort to design and implement intervention programs, develop prognostic models to achieve better care outcomes for EPLHIV. This cohort would provide vital information for stakeholders in HIV prevention, care and treatment to understand the characteristics of EPLHIV.

Epidemiologic and viral predictors of antiretroviral drug resistance among persons living with HIV in a large treatment program in Nigeria.

BACKGROUND: Expanded access to combination antiretroviral therapy (cART) throughout sub-Saharan Africa over the last decade has remarkably improved the prognosis of persons living with HIV (PLWH). However, some PLWH experience virologic rebound after a period of viral suppression, usually followed by selection of drug resistant virus. Determining factors associated with drug resistance can inform patient management and healthcare policies, particularly in resource-limited settings where drug resistance testing is not routine. METHODS: A case-control study was conducted using data captured from an electronic medical record in a large treatment program in Nigeria. Cases PLWH receiving cART who developed acquired drug resistance (ADR) and controls were those without ADR between 2004 and 2011. Each case was matched to up to 2 controls by sex, age, and education. Logistic regression was used estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with ADR. RESULTS: We evaluated 159 cases with ADR and 299 controls without ADR. In a multivariate model, factors associated with ADR included older age (OR = 2.35 [age 30-40 years 95% CI 1.29, 4.27], age 41 + years OR = 2.31 [95% CI 1.11, 4.84], compared to age 17-30), higher education level (secondary OR 2.14 [95% CI 1.1.11-4.13]), compared to primary and tertiary), non-adherence to care (OR = 2.48 [95% CI 1.50-4.00]), longer treatment duration (OR = 1.80 [95% CI 1.37-2.35]), lower CD4 count((OR = 0.95 [95% CI 0.95-0.97]) and higher viral load (OR = 1.97 [95% CI 1.44-2.54]). CONCLUSIONS: Understanding these predictors may guide programs in developing interventions to identify patients at risk of developing ADR and implementing prevention strategies.

Prevalence of hypertension among patients aged 50 and older living with human immunodeficiency virus.

BACKGROUND: Hypertension is one of the common medical conditions observed among patients aged 50 years and elder living with HIV (EPLWH) and to date no systematic review has estimated its global prevalence. PURPOSE: To conduct a systematic review to estimate the global prevalence of hypertension among EPLWH. DATA SOURCES: PubMed/MEDLINE, Embase, the Cochrane Library, and Global Health databases for relevant publications up till May 25, 2018. STUDY SELECTION: Observational studies (cohort or cross-sectional studies) that estimated the prevalence of hypertension among EPLWH. DATA EXTRACTION: Required data were extracted independently by three reviewers and the main outcome was hypertension prevalence among EPLWH. DATA SYNTHESIS: The 24 (n = 29,987) eligible studies included were conducted in North America, Europe, Africa, and Asia. A low level bias threat to the estimated hypertension prevalence rates was observed. The global prevalence of hypertension among EPLWH was estimated at 42.0% (95% CI 29.6%-55.4%), I = 100%. The subgroup analysis showed that North America has the highest prevalence of hypertension 50.2% (95% CI 29.2% -71.2%) followed by Europe 37.8% (95% CI 30.7%-45.7%) sub-Saharan Africa 31.9% (95% CI 18.5% -49.2%) and Asia 31.0% (95% CI 26.1%-36.3%). We found the mean age of the participants explaining a considerable part of variation in hypertension prevalence. CONCLUSION: This study demonstrated that two out of five EPLWH are hypertensive. North America appears to have the highest prevalence of hypertension followed by Europe, sub-Saharan Africa (SSA) and Asia respectively. Findings from this study can be utilized to integrate hypertension management to HIV management package. (Registration number: CRD42018103069).

Addressing the under-reporting of adverse drug reactions in public health programs controlling HIV/AIDS, Tuberculosis and Malaria: A prospective cohort study.

BACKGROUND: Adverse Drug Reactions (ADRs) are a major clinical and public health problem world-wide. The prompt reporting of suspected ADRs to regulatory authorities to activate drug safety surveillance and regulation appears to be the most pragmatic measure for addressing the problem. This paper evaluated a pharmacovigilance (PV) training model that was designed to improve the reporting of ADRs in public health programs treating the Human Immunodeficiency Virus (HIV), Tuberculosis (TB) and Malaria. METHODS: A Structured Pharmacovigilance and Training Initiative (SPHAR-TI) model based on the World Health Organization accredited Structured Operational Research and Training Initiative (SOR-IT) model was designed and implemented over a period of 12 months. A prospective cohort design was deployed to evaluate the outcomes of the model. The primary outcomes were knowledge gained and Individual Case Safety Reports (ICSR) (completed adverse drug reactions monitoring forms) submitted, while the secondary outcomes were facility based Pharmacovigilance Committees activated and health facility healthcare workers trained by the participants. RESULTS: Fifty-five (98%) participants were trained and followed up for 12 months. More than three quarter of the participants have never received training on pharmacovigilance prior to the course. Yet, a significant gain in knowledge was observed after the participants completed a comprehensive training for six days. In only seven months, 3000 ICSRs (with 100% completeness) were submitted, 2,937 facility based healthcare workers trained and 46 Pharmacovigilance Committees activated by the participants. Overall, a 273% increase in ICSRs submission to the National Agency for Food and Drug Administration and Control (NAFDAC) was observed. CONCLUSION: Participants gained knowledge, which tended to increase the reporting of ADRs. The SPHAR-TI model could be an option for strengthening the continuous reporting of ADRs in public health programs in resource limited settings.

Randomized trial evaluating self-sampling for HPV DNA based tests for cervical cancer screening in Nigeria.

BACKGROUND: Cervical cancer incidence and mortality rates in Sub-Saharan Africa (SSA) remain high due to several factors including low levels of uptake of cervical cancer screening. Self-collection of cervicovaginal samples for HPV DNA testing may be an effective modality that can increase uptake of cervical cancer screening in SSA and hard to reach populations in developed countries. We investigated whether self-collection of cervicovaginal samples for HPV DNA tests would be associated with increased uptake of screening compared with clinic based collection of samples. Furthermore, we compared the quality of samples collected by both approaches for use in HPV genotyping. METHODS: We conducted a community based randomized trial in a semi-urban district of Abuja, Nigeria with 400 women, aged 30 to 65 years randomized to either hospital-collection or self-collection of cervicovaginal samples. We compared cervical cancer screening uptake among the 2 groups and evaluated the concentration of human DNA in the samples by measuring RNase P gene levels using qPCR. High-risk HPV DNA detection and typing was done using the GP5+/6+ Luminex system. RESULTS: Most participants in the self-collection arm (93%, 185/200) submitted their samples while only 56% (113/200) of those invited to the hospital for sample collection attended and were screened during the study period (p value < 0.001). Human genomic DNA was detected in all but five (1.7%) participants, all of whom were in the self-collection arm. The prevalence of high-risk HPV in the study population was 10% with types 35, 52 and 18 being the commonest. CONCLUSIONS: Our study shows that self-sampling significantly increased uptake of HPV DNA based test for cervical cancer screening in this population and the samples collected were adequate for HPV detection and genotyping. Cervical cancer screening programs that incorporate self-sampling and HPV DNA tests are feasible and may significantly improve uptake of cervical cancer screening in SSA.

Prevalence of Hypertension and Its Associated Risk Factors among 34,111 HAART Naïve HIV-Infected Adults in Dar es Salaam, Tanzania.

Background. Elevated blood pressure has been reported among treatment naïve HIV-infected patients. We investigated prevalence of hypertension and its associated risk factors in a HAART naïve HIV-infected population in Dar es Salaam, Tanzania. Methods. A cross-sectional analysis was conducted among HAART naïve HIV-infected patients. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg. Overweight and obesity were defined as body mass index (BMI) between 25.0-29.9 kg/m2 and ≥30 kg/m2, respectively. We used relative risks to examine factors associated with hypertension. Results. Prevalence of hypertension was found to be 12.5%. After adjusting for possible confounders, risk of hypertension was 10% more in male than female patients. Patients aged ≥50 years had more than 2-fold increased risk for hypertension compared to 30-39-years-old patients. Overweight and obesity were associated with 51% and 94% increased risk for hypertension compared to normal weight patients. Low CD4+ T-cell count, advanced WHO clinical disease stage, and history of TB were associated with 10%, 42%, and 14% decreased risk for hypertension. Conclusions. Older age, male gender, and overweight/obesity were associated with hypertension. Immune suppression and history of TB were associated with lower risk for hypertension. HIV treatment programs should screen and manage hypertension even in HAART naïve individuals.

Doing no harm? Adverse events in a nation-wide cohort of patients with multidrug-resistant tuberculosis in Nigeria.

BACKGROUND: Adverse events (AEs) of second line anti-tuberculosis drugs (SLDs) are relatively well documented. However, the actual burden has rarely been described in detail in programmatic settings. We investigated the occurrence of these events in the national cohort of multidrug-resistant tuberculosis (MDR-TB) patients in Nigeria. METHOD: This was a retrospective, observational cohort study, using pharmacovigilance data systematically collected at all MDR-TB treatment centers in Nigeria. Characteristics of AEs during the intensive phase treatment were documented, and risk factors for development of AEs were assessed. RESULTS: Four hundred and sixty patients were included in the analysis: 62% were male; median age was 33 years [Interquartile Range (IQR):28-42] and median weight was 51 kg (IQR: 45-59). Two hundred and three (44%) patients experienced AEs; four died of conditions associated with SLD AEs. Gastro-intestinal (n = 100), neurological (n = 75), ototoxic (n = 72) and psychiatric (n = 60) AEs were the most commonly reported, whereas ototoxic and psychiatric AEs were the most debilitating. Majority of AEs developed after 1-2 months of therapy, and resolved in less than a month after treatment. Some treatment centers were twice as likely to report AEs compared with others, highlighting significant inconsistencies in reporting at different treatment centers. Patients with a higher body weight had an increased risk of experiencing AEs. No differences were observed in risk of AEs between HIV-infected and uninfected patients. Similarly, age was not significantly associated with AEs. CONCLUSION: Patients in the Nigerian MDR-TB cohort experienced a wide range of AEs, some of which were disabling and fatal. Early identification and prompt management as well as standardized reporting of AEs at all levels of healthcare, including the community is urgently needed. Safer regimens for drug-resistant TB with the shortest duration are advocated.