Baseline assessment of pharmacovigilance activities in four sub-Saharan African countries: a perspective on tuberculosis.

BACKGROUND: New medicines have become available for the treatment of drug-resistant tuberculosis (DR-TB) and are introduced in sub-Saharan Africa (SSA) by the national TB programs (NTPs) through special access schemes. Pharmacovigilance is typically the task of national medicines regulatory agencies (NMRAs), but the active drug safety monitoring and management (aDSM) recommended for the new TB medicines and regimens was introduced through the NTPs. We assessed the strengths and challenges of pharmacovigilance systems in Eswatini, Ethiopia, Nigeria and Tanzania, focusing on their capacity to monitor safety of medicines registered and not registered by the NMRAs for the treatment of DR-TB. METHODS: Assessment visits were conducted to all four countries by a multidisciplinary team. We used a pharmacovigilance indicator tool derived from existing tools, interviewed key stakeholders, and visited health facilities where DR-TB patients were treated with new medicines. Assessment results were verified with the local NMRAs and NTPs. RESULTS: Most countries have enabling laws, regulations and guidelines for the conduct of pharmacovigilance by the NMRAs. The relative success of NTP-NMRA collaboration is much influenced by interpersonal relationships between staff. Division of roles and responsibilities is not always clear and leads to duplication and unfulfilled tasks (e.g. causality assessment). The introduction of aDSM has increased awareness among DR-TB healthcare providers. CONCLUSION: aDSM has created awareness about the importance of pharmacovigilance among NTPs. In the future, a push for conducting pharmacovigilance through public health programs seems useful, but this needs to coincide with increased collaboration with between public health programs and NMRAs with clear formulation of roles and responsibilities.

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.

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.

Integrating community pharmacy into community based anti-retroviral therapy program: A pilot implementation in Abuja, Nigeria.

BACKGROUND: The landscape of Human Immunodeficiency Virus (HIV) epidemic control is shifting with the United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 benchmarks for epidemic control. Community-based Antiretroviral Therapy (CART) models have improved treatment uptake and demonstrated good clinical outcomes. We assessed the feasibility of integrating community pharmacy as a task shift structure for differentiated community ART in Abuja-Nigeria. METHODS: Stable patients on first line ART regimens from public health facilities were referred to community pharmacies in different locations within the Federal Capital Territory, Abuja for prescription refills and treatment maintenance. Bio-demographic and clinical data were collected from February 25, 2016 to May 31st, 2017 and descriptive statistics analysis applied. The outcomes of measure were prescription refill and patient retention in care at the community pharmacy. RESULTS: Almost 10% of stable patients on treatment were successfully devolved from eight health facilities to ten community pharmacies. Median age of the participants was 35 years [interquartile range (IQR); 30, 41] with married women in the majority. Prescription refill was 100% and almost all the participants (99.3%) were retained in care after they were devolved to the community pharmacies. Only one participant was lost-to-follow-up as a result of death. CONCLUSION: Excellent prescription refill and high retention in care with very low loss-to-follow-up were associated with the community pharmacy model. The use of community pharmacy for community ART is feasible in Nigeria. We recommend the scale up of the model in all the 36 states of Nigeria.

Adherence to Anti-Retroviral Therapy in North Central Nigeria.

BACKGROUND: Nigeria bears nearly 10% of the global burden of HIV/AIDS. Most of the AIDS patients dwell in the part of Nigeria known as the "North Central" geopolitical region. Sustaining HIV patients in this high risk region is critical for the overall success of the ART program in Nigeria. We assessed the level of adherence to ART and adherence determinants among participants who had been on ART for an average of three and half years. METHODOLOGY: Eligible study participants initiated HAART between 2004 and 2010. HAART regimens contained AZT/3TC +NVP or EFV; AZT/3TC/NVP; 3TC/NVP/d4T; TDF/FTC +EFV or NVP and TDF+3TC+LPV/r. A composite adherence measure defined as not missing a dose and taking the correct dose and adhering to the correct frequency and correct schedule of drug administration was used to assess self-reported adherence over a period of three days. Selfreported adherence was validated with viral load test. Base line adherence was fixed at ≥95% adherence level. Significant test was fixed at p<0.05. RESULTS: We included 502 participants in the analysis. Median age for men was 42 years (IQR: 38 - 44 years) and women, 36 years (IQR: 30-40 years). Mean duration of therapy was 43 (16-70) months. Effective self-reported adherence was 97.3%. Only age and virologic suppression were significantly associated with adherence to ART. Forgetfullness (43%) was the major reason for non-adherence, while improvement in health condition (40%) was the main facilitator of adherence to the medications. CONCLUSION: Most participants achieved optimal adherence (≥95%) with high virologic suppression. Strategies to sustain optimal adherence, e.g., the use of fixed dose combinations (FDCs) and comprehensive adherence counselling should be maintained.