Analysis of Pharmacovigilance Databases for Dolutegravir Safety in Pregnancy.

BACKGROUND: The Botswana Tsepamo study reported neural tube defects (NTDs) in 4 of 426 (0.94%) infants of women receiving preconception dolutegravir (DTG) antiretroviral therapy (ART) vs 14 of 11 300 (0.12%) receiving preconception non-DTG ART. Data are needed to investigate this potential safety signal. Clinicians, patients, and pharmaceutical companies can report adverse drug reactions (ADRs) to pharmacovigilance databases. Data from ADRs reported to various pharmacovigilance databases were searched for NTDs. METHODS: Four pharmacovigilance databases (World Health Organization [WHO] VigiAccess; United Kingdom Medicines Health Regulatory Authority [UK MHRA]; European Medicines Agency [EMA] EudraVigilance; US Food and Drug Administration Adverse Event Reporting System [FAERS]) with online data availability were analyzed for NTD reports for 4 integrase inhibitors (DTG, raltegravir, elvitegravir, bictegravir), 2 protease inhibitors (darunavir, atazanavir), and 2 nonnucleoside reverse transcriptase inhibitors (nevirapine, efavirenz). Reports in the system organ class "congenital or familial disorders" were searched for NTDs. RESULTS: NTDs have been reported among infants born from women taking a wide range of antiretrovirals in 4 pharmacovigilance databases (WHO VigiAccess, 116 reactions; UK MHRA, 8 cases; EMA EudraVigilance, 20 cases; FAERS, 44 cases). Six NTDs were identified for DTG across the pharmacovigilance databases. Cases were very hard to interpret, given the lack of clear denominators. CONCLUSIONS: Pharmacovigilance databases have many limitations, most importantly lack of a clear denominator for patients exposed to the drug of interest and duplicate cases that are difficult to identify. Given widespread use of new antiretroviral drugs worldwide and anticipated use of new drugs, prospective follow-up of pregnant women and birth surveillance studies such as Tsepamo are critically needed.

Most new HIV infections, vertical transmissions and AIDS-related deaths occur in lower-prevalence countries.

OBJECTIVES: The Joint United Nations Programme on HIV/AIDS (UNAIDS) targets aim to reduce new HIV infections below 500,000 per year by 2020. Despite targeted prevention programmes, total new infections remained in 2016 and 2017 at 1,800,000 cases. We have aimed to analyse data from 2017 and to compare HIV incidence, AIDS-related deaths and provision of antiretroviral therapy (ART) to adults, pregnant women and children living with HIV in lower- and higher-prevalence countries. Vertical or mother-to-child transmission (MTCT) and early infant diagnosis (EID) rates were also investigated. METHODS: UNAIDSinfo data use the Spectrum model to represent country-level HIV data. Countries with epidemics over 40,000 HIV cases were separated into higher prevalence (≥4.5%) and lower prevalence (<4.5%). Least squares linear regression, weighted by epidemic size and controlled for gross domestic product/capita, was used to compare HIV prevalence with estimated ART coverage in adults (≥15 years), children (0-14 years), pregnant women, and EID rates and MTCT rates. Data were then compared between higher- and lower-prevalence groups, including numbers of new HIV infections and AIDS-related deaths. RESULTS: Data were available for 56 countries. Twelve higher-prevalence countries accounted for 16.7 million and 44 lower-prevalence ones for 15.1 million people living with HIV, altogether making up 87.5% of the global estimate. Lower-prevalence countries had less ART coverage for adults, pregnant women and children, lower EID rates and higher AIDS-related death levels. There were more new HIV infections in adults and children in lower- than higher-prevalence countries. CONCLUSIONS: Most new HIV infections, MTCTs and AIDS-related deaths occurred in countries with an HIV prevalence rate below 4.5%. Many of these countries are not targeted by access programmes, such as the President' Emergency Plan for AIDS Relief. More intensive programmes of diagnosis and treatment are needed in these countries in the effort to reduce global new HIV infections below 500,000 per year by 2020.