Biomedical subjects

R Siliciano

Publications and source records attributed to R Siliciano.

6 recordsLinked to original sources

PubMed2000

Antiretroviral resistance during successful therapy of HIV type 1 infection.

HIV type 1 (HIV-1) drug resistance mutations were selected during antiretroviral therapy successfully suppressing plasma HIV-1 RNA to <50 copies/ml. New resistant mutant subpopulations were identified by clonal sequencing analyses of viruses cultured from blood cells. Drug susceptibility tests showed that biological clones of virus with the mutations acquired during successful therapy had increased resistance. Each of the five subjects with new resistant mutants had evidence of some residual virus replication during highly active antiretroviral therapy (HAART), based on transient episodes of plasma HIV-1 RNA > 50 copies/ml and virus env gene sequence changes. Each had received a suboptimal regimen before starting HAART. Antiretroviral-resistant HIV-1 can be selected from residual virus replication during HAART in the absence of sustained rebound of plasma HIV-1 RNA.

Anti-HIV Agents↗

PubMed2000

Can antiretroviral therapy ever be stopped?

A pool of latently infected CD4+ T cells is established within the first few weeks of HIV infection. Because these memory T cells are inactive, the viral DNA integrated into their chromosomes remains invisible to immune surveillance and to antiretrovirals. Research shows that this reservoir of infected memory T cells does not decay in a clinically meaningful time frame--that is, within 60 years--in patients being treated with potent combination antiretrovirals. Even a hypothetical regimen that prevents any new infection of cells would not hasten the decay of this latent reservoir. Treatments that activate this reservoir have been studied in patients with suppressed viremia, but such interventions are highly toxic and have not succeeded so far. Studying rare individuals who manage to control activation of these latent cells may provide important clues to long-term control of HIV infection.

Anti-HIV Agents↗

PubMed1999

Control of HIV despite the discontinuation of antiretroviral therapy.

Explore the source record for details and available documents.

Anti-HIV Agents↗

PubMed1999

HARRT for life.

Explore the source record for details and available documents.

Anti-HIV Agents↗

PubMed1998

Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. NIAID AIDS Vaccine Evaluation Group.

A safety and immunogenicity trial was conducted in vaccinia-immune and vaccinia-naive human immunodeficiency virus (HIV)-uninfected adults who were randomized to receive 10(6) or 10(7) TCID50 of canarypox (ALVAC) vector expressing HIV-1MN gp160 or 10(5.5) TCID50 of ALVAC-rabies virus glycoprotein control at 0 and 1 or 2 months and ALVAC-gp160 or 50 microg of HIV-1SF2 recombinant (r) gp120 in microfluidized emulsion at 9 and 12 months; others received rgp120 at 0, 1, 6, and 12 months. All vaccines were well-tolerated. Neither vaccinia-immune status before vaccination nor ALVAC dose affected HIV immune responses. HIV-1MN and HIV-1SF2 neutralizing antibodies were detected more often (100%) in ALVAC-gp160/rgp120 recipients than in recipients of ALVAC-gp160 (<65%) or rgp120 (89%) alone. ALVAC-gp160/rgp120 also elicited more frequent HIV V3-specific and fusion-inhibition antibodies, antibody-dependent cellular cytotoxicity, lymphoproliferation, and cytotoxic CD8+ T cell activity than did either vaccine alone. Trials with ALVAC expressing additional HIV components and rgp120 are underway.

AIDS Vaccines↗

PubMed1976

Relaxation phenomena in human erythrocyte suspensions.

Previous work has shown that the application of the Joule heating temperature jump technique of Eigen and de Maeyer to an istonic suspension of human erythrocytes induced an interiorization of [3H-A1glucose and a hemolysis of the red cells (Tsong, T.Y., and E. Kingsley, J. Biol. Chem. 250:786 [1975]). The result was interpreted as due to the thermal osmosis effect. Further considerations of the various effects of the Joule heating technique indicate that the hemolysis of the red cells may also be caused by the rapid dielectric perturbation of the cell membranes. By means of turbidity measurements of the suspensions we have detected at least four relaxation times. Two of the faster ones (tau1 approximately 20 mus and tau2 approximately 5 ms) are tentatively attributed to water relaxations in the membrane structures. The other two are attributed to membrane ruptures (tlag approximately 0.1s) and the hemolysis reaction (tau3 approximately 0.5 s). Studies with the erythrocytes from different hematological disorders indicate that whereas the two slower relaxations are sensitive to the overall physical property of the red cell membranes the two faster relaxations are not. These observations are consistent with the above assignment of the relaxation processes. The apparent activation energies are, above assignment of the relaxation processes. The apparent activation energies are, respectively, 8.4, 12.0, and 11.8 kcal/mol for the tau1, tau2, and tau3 reactions. Experiments with erythrocyte ghosts indicate a single relaxation for the water permeation, and biphasic kinetics for the membrane rupture and resealing reactions. The phenomena reported here may contribute to our understanding of water transport and molecular release in cellular systems.

Electricity↗