Protocol for active safety monitoring of a cohort of patients using a dolutegravir-based antiretroviral regimen in Mozambique.

INTRODUCTION: Dolutegravir-based antiretroviral therapy (ART) is increasingly being used as the preferred first-line regimen for the treatment of HIV in low-income and middle-income countries. The National Program for the Control of STI/HIV/AIDS in Mozambique has planned a phased introduction of the tenofovir/lamivudine/dolutegravir (TLD) regimen. In 2019, concerns about a potential safety signal identified with dolutegravir identified in the results of the Tsepamo study, conducted in Botswana, led the National Directorate of Pharmacy and the National Program for the Control of STI/HIV/AIDS to establish an active pharmacovigilance surveillance system among newly placed patients on a TLD regimen. This activity aims to establish an active pharmacovigilance system to monitor adverse events in patients on a TLD regimen to support the effectiveness of Mozambique's public health programmes in improving the process of care and treatment outcomes for people with HIV/AIDS. METHODS AND ANALYSIS: This is a prospective, non-interventional, descriptive cohort study to monitor HIV patients managed with TLD at 10 sentinel health centres in Mozambique. The cohort consists of HIV-infected patients commencing treatment with TLD, either as treatment naïve patients or switched from other ART regimens. Patients have monthly routine follow-up visits for the first 3 months after starting HIV treatment with TLD, and subsequently every 3 months for a total period of 1 year. Patients are monitored to identify possible adverse events during the follow-up period. The intended size of the cohort is 3000 patients. ETHICS AND DISSEMINATION: Ethical approval was obtained from the National Commission on Bioethics in Health in Mozambique. Written informed consent is obtained from each participant who agrees to participate to have their information collected, analysed and stored. Findings will be reported to the Ministry of Health and participating health centres to inform policy and practice as well as disseminated by peer-review publications.

Severe cutaneous adverse drug reactions manifesting as Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the national pharmacovigilance center in Nigeria: a database review from 2004 to 2017.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCARs). There is scant literature on the characteristics and causes of these conditions among the Nigerian population. Here, we describe the epidemiology, associated morbidity and mortality, and culpable drugs in SJS and TEN cases using the National Pharmacovigilance (NPC) database in Nigeria. METHODS: A retrospective review of the NPC database was done to analyze SJS and TEN cases reported over a period of 14 years. Annual reports, age and sex of patients, type of reporter, suspects and concomitant drugs, time to onset (TTO) of the reactions, and outcome of SJS and TEN were evaluated. RESULTS: The NPC received a total of 24,015 adverse drug reaction (ADR) reports. SJS and TEN accounted for 284 (0.1%) of the total reports, of which 254 (89.4%) were SJS and the remainder were TEN. Females (n = 184, 64.8%) and individuals aged 19-40 years (n = 181, 63.7%) were the most affected by SJS and TEN. Antiretrovirals, followed by antibiotics, were the most common drug classes reported to cause SJS and TEN, with nevirapine (n = 174, 40.7%) and co-trimoxazole (n = 143, 33.5%) being the most widely implicated drugs. Among patients with reported outcomes, 73 (28.7%) SJS and 3 (10.0%) TEN cases recovered without sequelae, at the time of reporting. Severity of the SCAR was reported for only 171 (69.0%) cases, of which 12 (4.7%) and 8 (26.7%) resulted in death (Grade 5) among SJS and TEN cases, respectively. CONCLUSIONS: Antiretroviral and antibiotics were the commonly reported offending group of drugs for SJS and TEN cases. Nevirapine and co-trimoxazole were the commonly reported suspect drugs. SJS and TEN were reported most frequently in females and in patients aged 19-40 years, indicating that drug surveillance and counseling in these groups of patients may be beneficial.

A Retrospective Review of Serious Adverse Drug Reaction Reports in the Nigerian VigiFlow Database from September 2004 to December 2016.

BACKGROUND: Adverse drug reactions (ADRs) are a source of concern in healthcare as they negatively affect patients. Serious adverse drug reactions (SADRs) have an even greater impact on patients and the system in terms of morbidity and financial burden. The establishment of National Pharmacovigilance Centers (NPCs) has enhanced ADR reporting in Africa. The Nigerian Pharmacovigilance Centre has been collecting ADR reports using VigiFlow since 2004. OBJECTIVE: The aim of this study was to identify and analyze SADR reports in the Nigerian VigiFlow database in order to profile the patients with SADRs, the medicines most implicated, system organ classes (SOCs) affected, outcome of such reactions, including fatalities, and ADR reporting trends over the years. We also looked at the data elements provided in the reports as a proxy measure of report quality. METHOD: We retrospectively assessed all individual case safety reports (ICSRs) received by the NPC in Nigeria and entered into VigiFlow as SADR reports between September 2004 and December 2016. We defined SADR as any untoward reaction to any medicine dose that resulted in death, required in-patient hospitalization or prolongation of existing hospitalization, resulted in congenital anomaly, persistent or significant disability/incapacity or was life-threatening. The suspected SADRs were analyzed at the Medical Dictionary for Regulatory Activities SOC and Preferred Term levels. RESULTS: A total of 11,222 ICSRs were entered into VigiFlow during the study period, of which 298 (3%) were classified as SADR reports. Adults were the most affected (244/282; 87%). The median number of medicines per report was 3 (interquartile range = 2-4.75). Nevirapine (36/336; 11%), as a single entity, was the most reported medicine. Human immunodeficiency virus (HIV) infection affected 128/232 (55%) of those with SADRs. There was no statistically significant association between the number of reactions per report and sex of the patients (p = 0.280), their age groups (p = 0.670), or the number of medicines per report (p = 0.640). Hospitalization was the most frequently cited reason for classifying a report as serious (151/276; 53%) and death was reported in 48 cases (48/283; 17%). Based on the SOC, skin and subcutaneous tissue disorders (139/550; 25%) was the most affected, while anemia (55/550; 10%) was the most reported specific reaction. A substantial number of patients (107/256; 42%) either recovered fully or were recovering from the SADRs. The number of SADR reports received varied by year with no consistent trend. CONCLUSION: There is under-reporting of ADRs in the Nigerian VigiFlow® database, particularly SADRs and those involving pediatric and geriatric age groups. Given that over half of the SADR reports involved antiretroviral drugs, it is imperative to increase the surveillance of ADRs related to this class of drugs through regular clinical assessment of reports and provision of feedback on the findings to healthcare providers. Direct consumer reporting should also be encouraged as a means of increasing ADR reporting.