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

Antibody response to hepatitis B vaccine in HIV-exposed infants in Malawi and correlation with HBV infection acquisition

The aim of this study was to assess the immune response to HBV vaccine in HIV-exposed infants and to correlate it to HBV infection acquisition. Protective anti-HBs levels (>10 mIU/mL) were found in 54/58 (93.2%) infants at 6 months, 126/144 (87.5%) at 12 months and 141/176 (80.1%) children at 24 months. HBV infection (seven children were HBsAg + at Month 24) occurred also in the presence of levels above 10 mIU/mL. Our findings indicate limited impact of HIV exposure on anti-HBV immune response, but suggest that levels >10 mIU/mL may be required to confer protection in this context

Modifications of HIV-1 DNA and provirus-infected cells during 24 months of intermittent highly active antiretroviral therapy

BACKGROUND: Few data have been reported on the dynamics of HIV-1 DNA during intermittent highly active antiretroviral therapy (HAART). In this study, we measured cell-associated HIV-1 DNA and provirus-infected cells during the Istituto Superiore di Sanit\ue0-Pulsed Antiretroviral Therapy (ISS-PART) clinical trial. METHODS: HIV-1 DNA was measured by real-time polymerase chain reaction (PCR) in the peripheral blood mononuclear cells (PBMCs) of 37 subjects enrolled in the ISS-PART, a randomized clinical trial comparing 24 months of intermittent (arm B) versus continuous (arm A) HAART in chronic HIV infection. In 14 subjects, the number of provirus-infected cells was also measured at baseline and at month 24. RESULTS: At baseline, the number of HIV-1 DNA copies/10(6) PBMCs was similar in arm B (mean +/- SD: 121 +/- 172, median = 35) and arm A (mean +/- SD: 107 +/- 153, median = 10) (P = not significant [n.s.]). No significant variations occurred over time; at 24 months, the HIV-1 DNA level was 77 +/- 28 (median = 30) copies/10(6) PBMCs in arm B and 166 +/- 321 copies/10(6) PBMCs (median = 10) in arm A (P = n.s.). At baseline, the provirus-infected cell counts were 85 +/- 98 (median = 50) cells/10(6) PBMCs in arm B and 92 +/- 113 (median = 50) cells/10(6) PBMCs in arm A (P = n.s.), with no variations at 24 months. CONCLUSIONS: These findings suggest that the intermittent schedule of the ISS-PART has no major impact on viral reservoirs, at least in a midterm follow-up