Activation and cell cycle antigens in CD4+ and CD8+ T cells correlate with plasma human immunodeficiency virus (HIV-1) RNA level in HIV-1 infection.

The relationship between T cell activation and human immunodeficiency virus type 1 (HIV-1) replication was studied in HIV-infected subjects, 20 with and 10 without anti-HIV treatment. Expression of Ki-67 proliferation-associated antigen was increased in CD4+ and CD8+ T cells and correlated with HLA-DR. In subjects without anti-HIV treatment, the plasma HIV-1 RNA level correlated with HLA-DR in CD4+ T cells, with Ki-67 in CD8+ T cells, and with expression of CD38 in both T cell subsets.

Efficacy of adding indinavir to previous reverse transcriptase nucleoside analogues in relation to genotypic and phenotypic resistance development in advanced HIV-1-infected patients.

We assessed the efficacy of adding indinavir in patients with advanced HIV-1 infection, who were previously exposed to different reverse transcriptase (RT) nucleoside analogues. Twenty-five patients with an initial median CD4 cell count of 20 cells/mm3 (range, 0-80 cells/mm3) were treated with indinavir (800 mg three times per day) for 24 weeks. The median initial viral load was 5.

Maximum cardiac output during incremental exercise by first-pass radionuclide ventriculography.

Study Objective: To validate a noninvasive first-pass radionuclide ventriculographic (FPRV) measurement of maximum cardiac output (Qv) during exercise.

Design: Comparison of Qv to that measured by the Fick principle (Qf) at peak exercise.

Setting: Academic cardiopulmonary exercise laboratory.

Cellular proviral HIV type 1 DNA load persists after long-term RT-inhibitor therapy in HIV type 1 infected persons.

In a set of 42 antiretroviral naive HIV-1 infected persons who were treated with either Zidovudine (AZT) monotherapy, or a combination of AZT + ddC (Zalcitabine) or AZT + ddI (Didanosine), the HIV-1 DNA load was measured by competitive polymerase chain reaction (PCR) and related to the HIV-1 RNA load in plasma, the CD4+ counts and to clinical markers. The question was whether a reduction in the cellular HIV-1 DNA level contributes to clinical benefit, as predicted by a lasting response in HIV-1 RNA levels in plasma. No significant decline relative to baseline in HIV-1 DNA load was found in the AZT monotherapy arm.

Efficient inhibition of both syncytium-inducing and non-syncytium-inducing wild-type HIV-1 by lamivudine in vivo.

Objective: To determine the effect of lamivudine (3TC) on syncytium-inducing (SI) and non-SI (NSI) HIV-1 populations in vivo.

Design: Responses in virus load and 3TC resistance in 40 3TC-treated subjects were analysed in relation to the presence or absence of SI HIV-1 variants.

Methods: Peripheral blood samples were collected at regular intervals from 40 HIV-1-infected subjects during 3TC treatment.

The duration of viral suppression during protease inhibitor therapy for HIV-1 infection is predicted by plasma HIV-1 RNA at the nadir.

Objective: To determine markers that are associated with the durability of virologic response to therapy with HIV protease inhibitors in HIV-infected individuals.

Design: This study encompassed two retrospective analyses of the duration of virologic response to protease inhibitor therapy. The first analysis included 29 patients receiving either monotherapy or combination therapy with the protease inhibitor ritonavir whose plasma HIV RNA levels rebounded from the point of greatest decline with mutations associated with resistance to ritonavir.

PrhA controls a novel regulatory pathway required for the specific induction of Ralstonia solanacearum hrp genes in the presence of plant cells.

The Ralstonia solanacearum hrp gene cluster is organized in five transcriptional units. Expression of transcriptional units 2, 3 and 4 is induced in minimal medium and depends on the hrp regulatory gene hrpB, which belongs to unit 1. This regulatory gene also controls the expression of genes, such as popA, located to the left of the hrp cluster.

In-vitro selection of HIV-1 variants resistant to non-nucleoside reverse transcriptase inhibitors in monocyte-derived macrophages.

Unlike the selection of HIV-1 variants resistant to anti-retroviral drugs in human peripheral blood mononuclear cells and T cell lines, induction of resistance in monocyte-derived macrophages has not been widely studied. Since macrophages serve as a potential HIV-1 reservoir in humans, knowledge of the effect of anti-retroviral drugs on macrophage-tropic HIV-1 isolates may help in the design of a strategy for prolonged suppression of viral replication. In-vitro selection and drug susceptibility testing of macrophage-tropic HIV-1 variants with reduced sensitivity to two non-nucleoside reverse transcriptase inhibitors, atevirdine and delavirdine (both bis-heteroarylpiperazines), is described here.

Selective inhibition of syncytium-inducing and nonsyncytium-inducing HIV-1 variants in individuals receiving didanosine or zidovudine, respectively.

By studying changes in the clonal composition of HIV-1 populations during the first weeks of zidovudine (ZDV) treatment before the development of ZDV resistance-conferring mutations, we demonstrated previously a selective inhibition of nonsyncytium-inducing (NSI) HIV-1, even when present as coexisting population in individuals also harboring syncytium-inducing (SI) HIV-1. In this study, we observed the opposite in individuals receiving didanosine (ddI) treatment. In these individuals (n = 7) a median -0.

HIV-1 viral load, phenotype, and resistance in a subset of drug-naive participants from the Delta trial. The National Virology Groups. Delta Virology Working Group and Coordinating Committee.

Background: The Delta trial showed that combination therapy (zidovudine plus didanosine and zidovudine plus zalcitabine) substantially lengthened life and reduced disease progression compared with zidovudine monotherapy. We did a nested virological study in three countries (France, the Netherlands, and the UK) to investigate changes in markers for viral load and antiretroviral-drug resistance during therapy.

Methods: 240 zidovudine-naive HIV-1-infected patients were randomly assigned zidovudine only (n = 87), zidovudine plus didanosine (n = 80), or zidovudine plus zalcitabine (n = 73).

Overshoot of HIV-1 viraemia after early discontinuation of antiretroviral treatment.

Objective: To determine whether, as predicted by predator-prey dynamics, early withdrawal of antiretroviral therapy, i.e. when the number of CD4+ lymphocytes is still elevated, results in an overshoot of HIV-1 viraemia due to infection of increased numbers of available target cells at that time.

Lamivudine-resistant human immunodeficiency virus type 1 variants (184V) require multiple amino acid changes to become co-resistant to zidovudine in vivo.

Exposure of human immunodeficiency virus to the nucleoside analogue lamivudine (3TC) rapidly selects for resistant variants with a valine at codon 184 (M184V) in the catalytic site of reverse transcriptase. In vitro, 184V demonstrated increased enzyme fidelity and suppressed zidovudine resistance. Clinical trials demonstrated that 3TC-zidovudine combination therapy results in a strong and sustained antiviral response.

Pancreatic GAPDH gene expression during ontogeny and acute pancreatitis induced by caerulein.

Recent studies indicated that expression of the housekeeping gene GAPDH is highly regulated during proliferation and differentiation. The objective of this study was to characterize by Northern blot the GAPDH mRNA expression in rat pancreas development and regeneration following acute pancreatitis induction by caerulein. Pancreatic GAPDH mRNA levels were the highest between fetal day 19 and the 11 postnatal day; they decreased to their lowest level after weaning on day 26.

Somatic instability of the myotonic dystrophy (CTG)n repeat during human fetal development.

Myotonic dystrophy is characterised by the striking level of somatic heterogeneity seen between and within tissues of the same patient, which probably accounts for a significant proportion of the pleiotropy associated with this disorder. The congenital form of the disease is associated with the largest (CTG)n repeat expansions. We have investigated the timing of instability of myotonic dystrophy (CTG)n repeats in a series of congenitally affected fetuses and neonates.

[AIDS; new developments. II. Treatment of HIV infection].

The currently available anti-HIV drugs can be subdivided according to the mechanisms of action into two main groups, viz, reverse transcriptase (RT) inhibitors and protease inhibitors; the former may be subdivided into nucleoside inhibitors and non-nucleoside inhibitors of reverse transcriptase. Combination therapy is preferable to monotherapy because of resistance problems. The 'ideal' combination consists of two RT inhibitors plus one protease inhibitor.

Results of long-term follow-up of HIV-infected patients treated with lamivudine monotherapy, followed by a combination of lamivudine and zidovudine.

The objective of this study was to determine the efficacy and safety of adding zidovudine to continuous treatment with lamivudine in symptomatic human immunodeficiency virus type 1 (HIV-1)-infected patients. Forty patients were monitored throughout lamivudine monotherapy and subsequent combination therapy with lamivudine and zidovudine, which was initiated because of disease progression, declining CD4 cell counts or prolonged use of lamivudine. Eleven of these patients had been treated with zidovudine before the start of the study.

HIV-1 RNA levels in the cerebrospinal fluid may increase owing to damage to the blood-brain barrier.

Human immunodeficiency virus type 1 (HIV-1) RNA can be detected in the cerebrospinal fluid (CSF) of 75-90% of all HIV-infected patients. However, it is not yet known which factors influence the amount of HIV-1 in the CSF, either qualitatively or quantitatively. We have analysed HIV-1 RNA in CSF samples from 24 HIV-infected patients using zidovudine who underwent lumbar puncture in order to establish a diagnosis for a neurological disorder.

European contribution to the science, prevention and management of HIV infection.

The objectives of the European Commission Biomed AIDS Programme are to enable Europe to pool its intellectual and financial resources in the control, treatment and prevention of HIV infection and AIDS. In order to facilitate this aim the Commission has allocated 40 to 50 million ECU over the past 6 years for concerted action of the Biomed projects on AIDS by the countries of the European Union. This is only a small proportion of the real cost spent by the member countries on this epidemic.

High-dose nevirapine in previously untreated human immunodeficiency virus type 1-infected persons does not result in sustained suppression of viral replication.

High-dose nevirapine treatment has been reported to confer sustained antiretroviral effects, despite a rapid development of resistance. The use of this strategy was evaluated in 20 previously untreated human immunodeficiency virus type 1 (HIV-1) p24 antigenemic persons with CD4 cell counts between 100 and 500/mm3. Treatment consisted of 400 mg of nevirapine, after a 2-week lead-in dose of 200 mg.

Initial appearance of the 184Ile variant in lamivudine-treated patients is caused by the mutational bias of human immunodeficiency virus type 1 reverse transcriptase.

Treatment of human immunodeficiency virus type 1-infected patients with lamivudine (3TC) results in the appearance of drug-resistant virus variants with a mutation at the 184Met codon (ATG) of the reverse transcriptase (RT) gene. The 184Ile (ATA) variant appears first, but subsequently the 184Val (GTG) variant outcompetes the 184Ile variant. We demonstrated previously that the 184Val enzyme and the corresponding virus are more fit than 184Ile, thereby explaining eventual outgrowth of 184Val.