Prevalence of HIV-1 pretreatment drug resistance among treatment naïve pregnant women in Bissau, Guinea Bissau.

BACKGROUND: With increased access to antiretroviral treatment (ART) in sub-Saharan Africa emergence of HIV-1 pretreatment drug resistance constitutes a serious risk. This may lead to rapid virological failure in subjects initiating ART, and mother-to-child transmission despite prophylaxis. METHODS: Treatment-naïve pregnant women from four antenatal care clinics in Bissau, Guinea-Bissau, were enrolled from October 2016 to November 2017. Genotypic resistance testing and phylogenetic subtype analysis was performed on 48 specimens. RESULTS: Forty eight women met the survey inclusion criteria. All specimens were successfully amplified and genotyped. Specimens from five women were associated with HIV-1 drug resistance mutations. Four carried mutations exclusively linked to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (K103N, K103N/S) and one carried mutations to both NNRTIs (G190S, K101E) and nucleoside reverse transcriptase inhibitors (NRTIs) (M184V). These results corresponded to 10.4% (95% CI: 4.5-22.2%), 2.1% (95% CI: 0.4-10.9%) and 0% (95% CI: 0.0-7.4%) drug resistance mutations to NNRTIs, NRTIs and protease inhibitors, respectively. HIV-1 circulating recombinant form 02AG was most commonly found, followed by HIV-1 sub-subtype A3. Subtype/CRF was not associated with drug resistance mutations. CONCLUSION: Our study reports a 10.4% prevalence of pretreatment drug resistance to NNRTIs in HIV-1-infected pregnant women in the capital Bissau, Guinea Bissau. Since NNRTIs are part of first-line ART in the country, baseline resistance screenings or adjustment of national treatment guidelines should be considered as antiretroviral treatment programs are scaled up.

Pancreatic cancer: the role of pancreatic stellate cells in tumor progression.

Pancreatic ductal adenocarcinoma is an aggressive and highly lethal disease frequently characterized by a dense stromal or desmoplastic response. Accumulating evidence exists that tumor desmoplasia plays a central role in disease progression and that e.g. activated pancreatic stellate cells (PSCs) are responsible for the excess matrix production. The mechanisms underlying the tumor versus stroma interplay are complex. Pancreatic cancer cells release mitogenic and fibrogenic stimulants, such as transforming growth factor ß(1), platelet-derived growth factor (PDGF), sonic hedgehog, galectin 3, endothelin 1 and serine protease inhibitor nexin 2, all of which may promote the activated PSC phenotype. Stellate cells in turn secrete various factors, including PDGF, stromal-derived factor 1, epidermal growth factor, insulin-like growth factor 1, fibroblast growth factor, secreted protein acidic and rich in cysteine, matrix metalloproteinases, small leucine-rich proteoglycans, periostin and collagen type I that mediate effects on tumor growth, invasion, metastasis and resistance to chemotherapy. This review intends to shed light on the mechanisms by which PSCs in the stroma influence pancreatic cancer development. The increased understanding of this interaction will be of potential value in designing new modalities of targeted therapy. and IAP.