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.

Impact of musculoskeletal symptoms on physical functioning and quality of life among treated people with HIV in high and low resource settings: A case study of the UK and Zambia.

BACKGROUND: Musculoskeletal symptoms in people living with HIV (PLWH) such as pain, joint stiffness, and fatigue are commonly reported. Prevalence rates of up to 45%, 79% and 88% respectively have been reported. However, very little is known about differences in prevalence and impact of musculoskeletal symptoms on physical functioning and quality of life of PLWH on effective combined antiretroviral treatment (cART) in high and low-resource settings. METHODS: A cross-sectional study of PLWH on effective cART enrolled from two large urban clinics in the UK and Zambia was conducted in 2016. Eligible participants had no history of trauma to the joints within 4 weeks of recruitment, or documented evidence of previous rheumatic disease. Current musculoskeletal symptoms, functional ability, and health-related quality of life were evaluated using the health assessment (HAQ) and quality-of-life short form (SF-36) self-reported questionnaires. RESULTS: 214 patients were enrolled (108:UK and 106:Zambia). Participants from Zambia were younger (47 vs 44 years) and had significantly lower CD4 counts (640 vs 439 cells/mL p = 0.018) compared to those from the UK, while the UK group had lived with HIV longer (11 vs 6 years; p<0.001) and reported more comorbidities than the Zambian group (66% vs 26%; p<0.001). Musculoskeletal pain was common in both groups (UK:69% vs Zambia:61% p = 0.263) but no significant differences in physical functional capacity between the groups were observed. However, the UK group had significantly worse quality of life measurements (general health, vitality, mental health, emotional, and social functioning) associated with musculoskeletal symptoms compared to the Zambian group (p<0.001). CONCLUSIONS: Musculoskeletal symptoms in PLWH from both the UK and Zambia were common. PLWH in the UK reported worse quality of life measures associated with musculoskeletal symptoms compared to those in Zambia, suggesting that factors such as mental health, patient expectations and multimorbidity might play a role in determining well-being and quality of life of PLWH with musculoskeletal symptoms.

Sporadic CJD in association with HIV.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive fatal neurodegenerative disorder. We report an unusual case of pathologically confirmed sporadic CJD developing in a HIV-positive patient but presenting with clinical and radiological features suggestive of variant CJD. CASE PRESENTATION: A 63-year-old man with chronic stable HIV developed progressive difficulties with decision-making, obsessive compulsive disorder and visual hallucinations over 3 months. CSF examination detected a weakly positive 14-3-3 protein, elevated S-100 protein, and siginificantly elevated total-Tau protein. Brain MRI revealed bilateral abnormal signal within the posterolateral thalami compatible with pulvinar sign. Further investigations revealed a negative tonsillar biospy and positive blood test consistent with variant CJD. However, prion protein genotyping detected MV heterozygosity at codon 129 and post-mortem histopathological examination was consistent with sporadic CJD. CONCLUSION: Although MRI findings were suggestive of variant CJD, the short residence in the UK and MV heterozygosity are aytpical, and the histopathological examination was consistent with sporadic CJD. With only two cases of HIV and sporadic CJD reported so far, the association of CJD with HIV remains unclear.