Impact of suppressive herpes therapy on genital HIV-1 RNA among women taking antiretroviral therapy: a randomized controlled trial

OBJECTIVE: To demonstrate a causal relationship between herpes simplex virus 2 (HSV-2) and increased genital HIV-1-RNA shedding in women on HAART. DESIGN: A randomized, double-blind, placebo-controlled trial of herpes-suppressive therapy (valacyclovir 500 mg twice a day) in HIV-1/HSV-2-infected women taking HAART in Burkina Faso. METHODS: Participants were followed for a total of 12 biweekly visits before and after randomization. The presence and frequency of genital and plasma HIV-1 RNA, and of genital HSV-2 were assessed using summary measures, adjusting for baseline values. Random effect linear regression models were used to assess the impact of treatment on genital and plasma viral loads among visits with detectable virus. RESULTS: Sixty women were enrolled into the trial. Their median CD4 lymphocyte count was 228 cells/mul, and 83% had undetectable plasma HIV-1 RNA at baseline. Valacyclovir reduced the proportion of visits with detectable genital HSV-2 DNA [odds ratio (OR) 0.37, 95% confidence interval (CI) 0.13, 1.05], but had no significant impact on the frequency (OR 0.90, 95% CI 0.31, 2.62) or quantity (reduction of 0.33 log copies/ml, 95% CI -0.81, 0.16) of genital HIV-1 RNA. However, according to pre-defined secondary analyses restricted to women who shed HIV-1 at least once in the baseline phase, valacyclovir reduced both the proportion of visits with detectable HIV-1 shedding (OR 0.27, 95% CI 0.07, 0.99) and the quantity of genital HIV-1 RNA during these visits (-0.71 log10 copies/ml, 95% CI -1.27, -0.14). CONCLUSION: HSV-2 facilitates residual genital HIV-1 replication among dually infected women taking HAART despite HIV-1 suppression at the systemic level.     

Patient-reported outcomes with direct-acting antivirals for the treatment of chronic hepatitis C: current knowledge and outstanding issues

Introduction: Patient-reported outcomes (PROs) play a key role in the evaluation of direct-acting antivirals (DAA) for the treatment of chronic hepatitis C (CHC). The main PROs of particular interest in CHC include quality of life (QoL), fatigue and its functional repercussions, work productivity, adherence to treatment, and risk behaviors.

Areas covered: This study summarizes the body of knowledge regarding PROs in CHC with DAA-based therapy. Outstanding related issues are presented and discussed.

Expert commentary: Current knowledge on PROs with CHC mainly relies on clinical trial data. All-oral DAA regimens are associated with minimal QoL impairment and symptom burden, rapid recovery once treatment has ended, and improvement in PROs for a non-negligible proportion of treated patients, especially HCV clearers. Further research is needed to analyze both long-term changes in PROs, and PROs in specific populations including people who use drugs, comorbid patients and patients at risk of reinfection.     

First report of a kdr mutation in Anopheles arabiensis from Burkina Faso, West Africa

The leu-phe kdr mutation was detected in a specimen of Anopheles arabiensis during an extensive survey of pyrethroid resistance in An. gambiae s.l. in Burkina Faso. The detection of this mutation in An. arabiensis, which had so far been observed only in An. gambiae s.s., is important at both epidemiologic and fundamental levels. It can be useful to understand the history of this gene throughout the range of An. gambiae complex.     

Hepatocellular carcinoma with normal adjacent liver. Hepatitis B virus DNA status

We investigated hepatitis B virus (HBV) DNA status in the liver of 22 patients with hepatocellular carcinoma (HCC) developed on a non-cirrhotic, histologically normal liver tissue. HBV serological markers were present in 2 of the 22 subjects. HBV DNA sequences were identified in the liver of only 5 of the 22 patients with HCC. Evidence for clonal expansion of HBV-infected cells was found for one HBsAg-positive subject. This study indicates a much lower rate of HBV DNA positivity in the group of HCC developed on histologically normal livers as compared to that observed in HCC with liver cirrhosis.     

Anti-pre-S responses and viral clearance in chronic hepatitis B virus infection.

Serial sera were collected prospectively during the clinical course of 13 HBsAg carriers with chronic liver disease and analyzed for ALT levels, pre-S1 and pre-S2 antigens and corresponding antibodies and other serological hepatitis B virus markers. In five patients, anti-pre-S1 and anti-pre-S2 antibodies became detectable in multiple serum samples, whereas in eight patients anti-pre-S was never detected or only appeared transiently during the follow-up. The first pattern was associated with normalization of ALT levels and undetectable pre-S antigens and viral DNA by the polymerase chain reaction assay at final follow-up. HBsAg clearance occurred in two of the five patients. The second pattern was one of persistence of HBsAg and pre-S antigens, associated with the presence of serum HBV DNA detectable by spot hybridization or polymerase chain reaction regardless of clinical outcome. These findings demonstrate the occurrence of anti-pre-S antibodies in chronic hepatitis B virus-induced liver disease and associate anti-pre-S appearance with the clearance of hepatitis B virus from serum.     

Role of the L-arginine-NO pathway and of cyclic GMP in electrical field-induced noradrenaline release and vasoconstriction in the rat tail artery.

1. The possible roles of the L-arginine-NO pathway and of guanosine 3':5'-cyclic monophosphate (cyclic GMP) in regulating the prejunctional release of noradrenaline and neurogenic vasoconstriction were investigated in the perfused rat tail artery. 2. In the presence of N omega-nitro-L-arginine methyl ester (L-NAME; 30 microM), an inhibitor of NO formation, the vasoconstrictor responses to perivascular nerve stimulation (24 pulses at 0.4 Hz, 0.3 ms, 200 mA) and to exogenous noradrenaline (1 microM) were significantly enhanced, whereas the stimulation-evoked tritium overflow from [3H]-noradrenaline preloaded arteries was not modified. The vasoconstriction enhancing effect of L-NAME was prevented by L-arginine (1 mM) but not D-arginine (1 mM) and was abolished by removal of the endothelium. 3. The NO donor, 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1; 0.1-30 microM), and the cyclic GMP phosphodiesterase inhibitor, zaprinast (0.1-30 microM) both induced a concentration-dependent inhibition of the electrical field stimulation-induced vasoconstriction, while atrial natriuretic peptide (ANP; 100 nM) produced only a slight decrease of the vasoconstrictor response. Methylene blue (3 microM), a known inhibitor of soluble guanylate cyclase increased the electrical field stimulation-induced vasoconstriction. SIN-1 and methylene blue when administered simultaneously, antagonized each others effect. None of the compounds tested (SIN-1, zaprinast, ANP or methylene blue) had any significant effect on the stimulation-evoked [3H]-noradrenaline overflow. 4. 8-Bromo-cyclic GMP, a potent activator of cyclic GMP-dependent protein kinase, markedly and concentration-dependently (3-300 microM) increased [3H]-noradrenaline overflow but decreased field stimulation-induced vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)