HIV-1 viral load and resistance in genital secretions in patients taking protease-inhibitor-based second-line therapy in Africa

Background: HIV is transmitted primarily through sexual intercourse, and the objective of this study was therefore to assess whether there is occult viral replication and resistance in genital secretions in patients on protease inhibitor (PI)-based second-line therapy. Methods: HIV-infected adults taking ritonavir-boosted lopinavir with either two NRTIs, raltegravir, or as monotherapy for 96 weeks were enrolled at seven clinical sites in Uganda. Viral load (VL) was measured in cervico-vaginal secretions or semen and in a corresponding plasma sample. Genotypic resistance was assessed in genital secretion samples and plasma samples. Results were compared between compartments and with the plasma resistance profile at first-line failure. Results: Of the 111 participants enrolled (91 female, 20 male), 16 (14%) and 30 (27%) had VL >1000 and >40 copies/ml respectively in plasma; 3 (3%) and 23 (21%) had VL >1000 copies/ml and >40 copies/ml respectively in genital secretions. There was 74% agreement between plasma and genital secretion VL classification above/below 40 copies/ml threshold (kappa-statistic=0.29; p=0.001). RT mutations (both NRTI and NNRTI) were detected in genital secretions in 4 patients (similar profile to corresponding plasma sample at first-line failure) and PI mutations were detected in 2 (1 polymorphism with no impact on resistance; 1 with high-level PI resistance). Conclusions: High level (>1000 copies/ml) viral replication and development of new RT or PI resistance in the genital compartment were rare. The risks of transmission arising from resistance evolution in the genital compartment are likely to be low on PI-based second-line therapy

Effect of antibiotics on polycation-treated Escherichia coli HB101(pRI203)

In the present paper, we demonstrated that low concentrations of various polycationic agents sensitize E. coli HB 101 harboring the plasmid pRI203, containing the Y. pseudotuberculosis invasion region, to antibiotics rifampicin, amikacin, ceftazidime and cefotaxime. These antibiotics, known to be excluded, to various degrees, by the bacterial outer membrane, resulted several-fold more active towards polycation-treated bacteria by comparison with controls. This increased permeability to antibiotics of E. coli HB 101 (pRI203) probably depends upon the binding of polycations to the acidic moieties of lipopolysaccharide, as already suggested for other gram-negative bacteria