Re-analysis of a human hepatitis B virus (HBV) isolate from an East African wild born Pan troglodytes schweinfurthii: evidence for interspecies recombination between HBV infecting chimpanzee and human.

According to current estimates, hepatitis B virus (HBV) has infected 2 billion people worldwide and among them, 360 million suffer from chronic HBV infection. Except humans, HBV or HBV-like viruses have also been isolated from different species of apes and mammals. Although recombination has been described to occur extensively between different genotypes within the human HBV lineage, no recombination event has ever been reported between human and non-human primate HBV sequences. It was our objective to perform an exhaustive search for recombination between human and non-human primate HBV strains among all available full-length human and non-human primate HBV sequences, using bootscanning and phylogenetic analyses. Intriguingly, we found that an HBV sequence isolated from a wild born Pan troglodytes schweinfurthii in East Africa-FG-is a recombinant consisting of HBV infecting chimpanzee (ChHBV) and human genotype C. More specifically, in a fragment of approximately 500 nt (positions 551-1050 spanning half of the RT domain of pol, which overlaps with half of the coding region of the small surface protein), FG grouped with HBV genotype C, while in the rest of the genome it grouped with ChHBV sequences. Phylogenetic analyses showed that in the latter region FG was more closely related to the Pan troglodytes troglodytes subspecies, forming an outlier to this group. Moreover, we show evidence that the recombination event occurred after the initial dispersion of HBV genotype C in humans. Finally, our findings point out that although rare recombination between HBV viruses infecting different species occurs.

Cellular HIV-1 DNA load predicts HIV-RNA rebound and the outcome of highly active antiretroviral therapy.

OBJECTIVE: To assess whether cellular HIV-1 DNA prior to highly active antiretroviral therapy (HAART) initiation predicts its outcome. DESIGN AND METHODS: Patients included all 51 hemophiliacs of the Greek component of the Multicenter Hemophilia Cohort Study who had initiated HAART and for whom cryopreserved lymphocyte samples before HAART initiation were available. Cellular HIV-1 DNA quantification was performed by a molecular beacon-based real-time PCR assay in multiple samples per patient with a median (interquartile range) follow-up of 76 (45-102) weeks. RESULTS: The median (range) baseline HIV-1 DNA load was 297 (< 10 to 3468) copies per 1 x 10(6) peripheral blood mononuclear cells. Baseline HIV-1 DNA load did not predict initial virological response (VR). None of the patients with initial VR and baseline HIV-1 DNA load at or below the median experienced a subsequent virological rebound, while the cumulative probability of virological rebound by week 104 was 55% among those with HIV-1 DNA load greater than the median (P < 0.008). Cellular HIV-1 DNA load was the only parameter associated with sustained virological response as shown by univariate or multivariate analyses [adjusted odds ratio (95% confidence interval) 0.197 (0.048-0.801) per 1 log10 increase in DNA copies, P = 0.023]. CONCLUSION: Low cellular HIV-1 DNA load is a marker of sustained virological response in patients with initial VR and it can reliably predict the long-term success of HAART.

Clinical evaluation of an HIV-1 and HCV assay and demonstration of significant reduction of the HCV detection window before seroconversion.

BACKGROUND: One HIV-1 and HCV assay simultaneously detects HIV-1 and HCV RNA (Procleix, Chiron Corp.). The main intended use of the assay is the testing of blood and blood products in blood banking. STUDY DESIGN AND METHODS: To evaluate the clinical sensitivity of the assay, 164 anti-HIV-1+ and 160 anti-HCV+ patients of different viral load were tested. The assay specificity was determined in 1000 HIV-1- and HCV-seronegative blood donors. The ability of the assay to detect different HCV genotypes was investigated in a total of 40 patients of different genotypes (1-4). Furthermore, to investigate the reduction of the HCV window phase before seroconversion, serial samples of 25 hemodialysis patients who seroconverted to anti-HCV were also tested. RESULTS: The assay detected all 60 HIV-1-infected patients with a viral load of greater than 50 copies per mL and 48 of 104 patients with a viral load of less than 50 copies per mL. Moreover, all 60 patients with an HCV RNA load of greater than 521 IU per mL and 7 of 100 patients with a viral load of less than 50 IU per mL tested positive. The assay specificity was found to be 100 percent. In addition, all 40 patients of different HCV genotypes were successfully detected. Finally, the median time that the assay detected HCV infection before second- and third-generation anti-HCV assay was found to be 183 and 91 days, respectively. CONCLUSION: The assay sensitivity and specificity, its ability to detect different HCV genotypes, and the significant reduction of window period of HCV infection further support its use for improving the safety of blood and blood products.

IFN-alpha2b monotherapy in patients with chronic hepatitis C and persistently normal or near normal aminotransferase activity: a randomized, controlled study.

To determine the effect of interferon-alpha2b (IFN-alpha2b) on the long-term suppression of hepatitis C virus (HCV) RNA in patients with persistently normal or near normal alanine aminotransferase (ALT) activity, 76 previously untreated patients with serum HCV RNA and ALT levels <1.5 times the upper limit of normal (ULN) were randomized to receive either interferon-alpha2b (IFN-alpha2b) 5 MU three times a week for 24 weeks (n = 37) or no treatment (n = 39). HCV RNA testing was performed at the end of treatment and after a 6-month follow-up period. Intention-to-treat analysis showed that HCV RNA was detected significantly less frequently in treated than in untreated patients, at the end of both treatment and follow-up (43.2% vs. 7.7%, p < 0.001, and 21.6% vs. 5.1%, p = 0.033, respectively). Among treated patients, sustained virologic response was significantly higher in non-1 than in genotype 1 patients (8 of 26 or 30.8% vs. 0 of 11, p = 0.038). According to multiple logistic regression, untreated patients had a 13.5 times greater risk to be HCV RNA-positive compared with treated patients (p = 0.040). ALT levels flared up in 3 treated and 9 untreated patients (p = 0.07), suggesting that these flare-ups are related to the natural course of chronic HCV infection rather than to IFN-alpha2b. Thus, such patients could benefit from an IFN-alpha2b in combination with ribavirin regimen.