The hope for an HIV vaccine based on induction of CD8+ T lymphocytes: a review

The only long-term and cost-effective solution to the human immunodeficiency virus (HIV) epidemic in the developing world is a vaccine that prevents individuals from becoming infected or, once infected, from passing the virus on to others. There is currently little hope for an AIDS vaccine. Conventional attempts to induce protective antibody and CD8+ lymphocyte responses against HIV and simian immunodeficiency virus (SIV) have failed. The enormous diversity of the virus has only recently been appreciated by vaccinologists, and our assays to determine CD8+ lymphocyte antiviral efficacy are inadequate. The central hypothesis of a CTL-based vaccine is that particularly effective CD8+ lymphocytes directed against at least five epitopes that are derived from regions under functional and structural constraints will control replication of pathogenic SIV. This would be somewhat analogous to control of virus replication by triple drug therapy or neutralizing antibodies.

Comparison of interferon monotherapy with interferon-lamivudine combination treatment in children with chronic hepatitis B.

AIM: To compare interferon monotherapy with combination treatment using interferon and lamivudine in children with chronic hepatitis B. METHODS: Data from 65 children who had received either interferon-alpha (5 MU/m2 subcutaneous thrice a week for 6 months; n=35; Group 1) or this dose of interferon-alpha for 6 months with oral lamivudine for one year (4 mg/Kg/day, maximum 100 mg/day; n=30; Group 2) were analyzed retrospectively. Complete response was defined as ALT normalization, HBeAg/anti-HBe seroconversion and HBV DNA clearance. RESULTS: ALT normalization rates were similar in Groups 1 and 2 at the end of interferon treatment (13 [38%] and 16 [52%], respectively), at 12 months (19 [56%] and 18 [58%]) and at 24 months (24 [71%] and 23 [74%]). HBV DNA clearance was more frequently observed at 6 months in Group 2 than in Group 1 (19 [63%] versus 7 [20%]; p=0.01), but not at 12 months (19 [63%] versus 17 [49%]) or at 24 months (20 [67%] versus 21 [60%]). Rate of HBeAg/anti-HBe seroconversion was higher in Group 2 at 12 months (18 [60%] versus 11 [31%]; p< 0.05). Rate of complete response was similar in Groups 1 and 2 at 6 months (5 [14%] and 10 [33%], respectively), 12 months (14 [40%] and 17 [57%]) and 24 months (20 [57%] and 19 [63%]). CONCLUSION: Although lamivudine and interferon combination achieved higher initial rates of HBV DNA loss and HBeAg/anti-HBe seroconversion than interferon alone, the final response rates were similar with the two treatments. The combination treatment is therefore not indicated for chronic hepatitis B in children.

A study on efficacy of lamivudine therapy in decompensated cirrhosis of liver due to chronic hepatitis B virus infection.

The prognosis of decompensated cirrhosis of liver resulting from chronic Hepatitis B Virus (HBV) infection is poor and liver transplantation is the only established mode of treatment. The benefits of treatment with interferon are outweighed by serious side effects and risks of fatal exacerbation of disease activity. Lamivudine rapidly reduces hepatitis B viral DNA in serum to undetectable levels. The purpose of this study was to evaluate effectiveness and safety of Lamivudine treatment in patients with advanced and end stage liver disease caused by Hepatitis B. This was a prospective observational study in which a total of 45 patients, 39 (87.0%) male and 6 (13.0%) female who had viral activity and child pugh score e" 8 were given Lamivudine 100 mg orally once daily. Among them 30 patients completed at least 6 months of therapy, majority (27 patients) showed improvement in liver function with decrease in serum ALT from mean (+/- SD) 118.8 +/- 106.5 to 50.2 +/- 57.1 U/L (p < 0.001), decrease in serum bilirubin from 73.9 +/- 80.5 to 44.7 +/- 62.9 micromol/l (p = 0.129), increase in serum albumin from 26.2 +/- 4.2 to 33.2 +/- 3.4 g/l (p < 0.05), decrease in prothrombin time from 8.3 +/- 4.0 to 3.9 +/- 2.9 seconds prolonged (p < 0.05) and reduction in child pugh score from 11.0 +/- 1.7 to 7.0 +/- 1.3 (p < 0.001). Seroconversion was found in 5 (11.1%) patients on Intention to treat analysis. Among the seroconverted group, 1 (2.2%) patient also lost HBsAg. Six (13.0%) patient had procore mutant virus, 2 (4.4%) of them showed virological response. Therefore, total 7 (15.5%) patients showed virological response by intention to treat analysis. We conclude that inhibition of viral replication with Lamivudine results in a significant improvement of liver function in patients with decompensated cirrhosis of liver due to HBV infection.

Ophthalmic antiviral chemotherapy: an overview.

Antiviral drug development has been slow due to many factors. One such factor is the difficulty to block the viral replication in the cell without adversely affecting the host cell metabolic activity. Most of the antiviral compounds are analogs of purines and pyramidines. Currently available antiviral drugs mainly inhibit viral nucleic acid synthesis, hence act only on actively replicating viruses. This article presents an overview of some of the commonly used antiviral agents in clinical ophthalmology.