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Biomedical subjects

S Yerly

Publications and source records attributed to S Yerly.

At least 55 records · Page 3Linked to original sources
PubMed1997

Zidovudine plus didanosine in primary HIV-1 infection.

Viraemia levels in the months following primary HIV-1 infection (PHI) predict the subsequent course of the infection. Inhibition of viral replication in PHI patients might improve their clinical prognosis. In this study, we evaluated the antiviral efficacy of the association of two reverse transcriptase inhibitors--zidovudine at 250 mg twice daily and didanosine at 200 mg twice daily--in 12 patients treated for at least 6 months (median 10 months, range 6-15 months). We compared values for viraemia, proviral DNA and CD4:CD8 ratios in these patients with two historical control groups consisting of 16 untreated patients and 15 patients on zidovudine therapy. Significantly lower viraemia was observed between 3 and 12 months in patients on zidovudine-didanosine therapy. Viraemia levels lower than 200 HIV-1 RNA copies/ml were observed in 3/12 patients on zidovudine-didanosine therapy after 3 months, in 8/12 after 6 months and in 3/5 after 12 months. Only one of the 31 historical control patients had undetectable viraemia. For proviral DNA, smaller differences between groups were observed, although with time proviral DNA became undetectable (< 1 copy/7.5 x 10(5) lymphocytes) in four patients from the zidovudine-didanosine group versus one in the control groups. Finally, the CD4:CD8 ratio was significantly higher in the zidovudine-didanosine group and none of the patients in this group developed HIV-1-associated clinical complications. These data suggest a higher efficacy of combined therapy compared with zidovudine monotherapy in PHI patients and indicate that control of viraemia for at least 1 year is achievable in PHI patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[Prevalence of transmission of zidovudine-resistant viruses in Switzerland. l'Etude suisse de cohorte VIH].

Zidovudine (ZDV) was the most widely used anti-HIV drug between 1987 and 1995, and, as already reported, transmission of ZDV-resistant viruses occurs. Several mutations of the reverse transcriptase gene have been identified; one of them affects the 215 codon and is associated with a high degree of resistance. We have determined, using selective PCR, the prevalence of transmission of 215 mutant isolates in 134 patients with primary HIV infection (PHI) and have identified 8 patients with 215 mutant virus between 1989 and 1995 in Switzerland. Mutant resistant viruses have been isolated from patients treated with most antiviral drugs. A systematic search for mutant viruses may provide useful information for the adaptation of treatment strategies.

Adolescent↗
PubMed1996

Prognostic value of viremia in patients with long-standing human immunodeficiency virus infection. Swiss HIV Cohort Study Group.

Human immunodeficiency virus (HIV) viremia was evaluated in 73 patients with long-standing infection to investigate its relationship with clinical or biologic parameters and to assess its use as a predictor of clinical progression and death. After adjustment for other parameters, baseline HIV RNA level was significantly associated with baseline clinical stage and CD4 cell count. During follow-up (mean, 14.6 months), 16 patients died; 34 others had clinical progression of disease. In multivariate analysis, mortality was better predicted by baseline CD4 cell count (relative hazard [RH] for 100-cell decrease, 3.5; 95% confidence interval [CI], 1.5-8.2; P = .003) than by HIV RNA (P = .28) or clinical stage. HIV RNA level was the best predictor of clinical progression (RH for 1 log increase, 2.8; 95% CI, 1.6-4.9; P < .001). Monitoring of HIV RNA level may help to identify patients who might benefit from antiretroviral or prophylactic therapy.

Adult↗
PubMed1996

Combined therapy with zidovudine and L-697,661 in primary HIV infection.

OBJECTIVE: To decrease viraemia levels in primary HIV infection by using a combination of zidovudine (ZDV) and L-697,661. DESIGN: Four primary HIV-infected patients were treated for 6 months with ZDV, 250 mg twice daily, in association with the non-nucleoside reverse transcriptase inhibitor L-697,661 500 mg three times daily. Viraemia, proviral DNA, CD4 and CD8 cell counts were measured serially during 18 months. RESULTS: Viraemia decreased to undetectable levels (< 200 RNA copies/ml) in two patients. A third patient had a marked decrease followed by a rebound during therapy; viraemia levels did not vary markedly in the fourth patient. A rebound in viraemia levels was observed within 15 days of discontinuation of therapy in the three responding patients. Proviral levels evolved in parallel with viraemia but were always detectable in all patients. In the three patients with an initial decrease of viraemia, CD4 cell counts were within the normal range 2 months after initiation of therapy and did not markedly decrease after discontinuation of therapy. In the two patients with partial or no response of viraemia, mutations associated with low level of resistance to L-697,661 appeared during treatment. CONCLUSION: A marked decrease of viraemia can be achieved in some primary HIV-infected patients with combined therapy. Six months of treatment does not prevent a rebound of viraemia, which was observed within 15 days of interruption of therapy.

Adult↗
PubMed1996

Rapid and sensitive detection of enteroviruses in specimens from patients with aseptic meningitis.

A 5-h PCR assay (Amplicor enterovirus test) was compared with viral culture for the detection of enteroviruses in cerebrospinal fluid. Of the cerebrospinal fluid specimens collected during a summer outbreak of aseptic meningitis, 34% were positive by viral culture whereas 66% were positive by the Amplicor PCR, suggesting that this technique improves the diagnosis of enteroviral meningitis.

Base Sequence↗
PubMed1996

Predictive value of codon 215 reverse transcriptase mutation on the efficacy of didanosine in HIV-infected, zidovudine-experienced patients.

We investigated whether or not mutations at codon 215 in the HIV reverse-transcriptase-encoding gene predicted a lower efficacy of didanosine therapy, as defined by survival of patients and change in CD4 cell counts in 121 HIV-infected, zidovudine-experienced patients. A trend for shorter survival, although not reaching significance, was observed for patients with HIV strains with the reverse transcriptase codon 215 mutation (P = 0.07), but this trend disappeared after adjustment for initial CD4 cell counts. During the first 3 months on didanosine therapy, the increase in CD4 cell counts was greater in patients who were wild type at codon 215 than in those with the mutation at codon 215 (P = 0.03). These data suggest that there was a better initial CD4 response to didanosine therapy in patients with HIV without the mutation at codon 215, but that this response did not translate into increased survival.

Anti-HIV Agents↗
PubMed1995

Early and prolonged decrease of viremia in HIV-1-infected patients treated with didanosine.

Fourteen patients previously treated with zidovudine were monitored for laboratory parameters and clinical events during 1 year after introduction of didanosine (ddI) monotherapy. Proviral human immunodeficiency virus type 1 (HIV-1) copy numbers (cell-associated DNA) and concentration of free virions (viremia) were determined using a semiquantitative polymerase chain reaction (PCR). High levels of circulating virus were detected in all patients (range, 17 to 5,934 x 10(3)/ml of serum). Within 4 weeks of therapy, a decrease of viremia (60 to 98%) was observed in nine patients. After 1 year of treatment, eight of these nine patients still had decreased viremia when proviral HIV DNA was decreased or stable, and CD4+ lymphocytes were stable or higher in seven of these eight patients. Antiviral effect was more pronounced in the six patients with CD4+ > 100/mm3 at entry, five of them belonging to the subgroup of the seven responding patients as compared to two of eight patients with CD4+ < 100/mm3. Clinical events in this small group were not statistically correlated with virologic parameters; however, responding patients had a tendency to stabilize or gain weight. This study suggests that measurement of viremia deserves further study as a marker of antiviral efficacy and might predict, even at 4 weeks, the beneficial potential of ddI.

AIDS-Related Opportunistic Infections↗
PubMed1995

Foscarnet decreases human immunodeficiency virus RNA.

Foscarnet inhibits human immunodeficiency virus (HIV) replication in vitro and decreases p24 antigenemia in patients with cytomegalovirus (CMV) retinitis. To evaluate the effect of foscarnet on HIV replication, HIV RNA was quantitated in 17 patients before and during foscarnet therapy. Fifteen patients had CMV retinitis, 1 had CMV encephalitis, and 1 had intractable zoster. A decrease in HIV RNA was observed in 16 of 17 patients. Before the introduction of foscarnet, mean HIV RNA was 5.82 +/- 0.24 log RNA/mL and, after a median of 13 days of therapy, mean HIV RNA was 5.30 +/- 0.27 log RNA/mL (P < .001). Among patients with detectable p24 antigen at baseline, a significant decrease was observed (P = .017). This decrease in HIV RNA demonstrates that foscarnet is a potent antiretroviral drug.

AIDS-Related Opportunistic Infections↗
PubMed1995

V3 sequences in primary HIV-1 infection.

OBJECTIVE: To determine HIV-1 genomic RNA and proviral DNA sequences of the third hypervariable region (V3 loop) of the envelope protein in patients with primary HIV-1 infection (PHI), and to compare these sequences with sequences from patients with more advanced HIV-1 infection. METHODS: Sera and peripheral blood mononuclear cells were collected from 24 patients with PHI living in Geneva. V3 sequences were determined using direct solid-phase sequencing on polymerase chain reaction (PCR) products. RESULTS: A 100% homology rate was observed between HIV-1 genomic RNA and proviral DNA paired nucleotide sequences from the V3 region in the 24 patients. Using a limiting dilution approach for three patients, a unique V3 sequence was observed for the genomic RNA. Three out of 24 amino-acid sequences presented the characteristic signature sequence QRGPGR, first described for the HIV-1LAI isolate, which is associated with lymphocytotropism. These three isolates also presented, for the V3 loop, a characteristic elevated charge (8) at physiological pH in comparison with the other isolates (3-5). There was no significant difference in the distribution of amino acids between the 24 V3 loop sequences from patients with PHI and 245 V3 loop sequences of the B subtype determined in patients with more advanced HIV-1 infection. CONCLUSION: The paired sequences recovered from HIV-1 genomic RNA and proviral DNA are identical for each of the 24 patients with PHI. Three isolates had the V3 loop characteristic signature sequence QRGPGR first described for the HIV-1LAI isolate. There is no characteristic V3 loop pattern associated with PHI isolates.

Adult↗
PubMed1995

Response of HIV RNA to didanosine as a predictive marker of survival.

OBJECTIVE: To evaluate whether early changes in viraemia in response to didanosine (ddI) predict death and occurrence of new AIDS-defining events. METHODS: Forty-three patients were followed during ddI treatment with sequential determinations of serum viraemia, mutations associated with drug resistance, CD4 counts and clinical evaluation. Patients were stratified into two groups of equal size, responders and nonresponders, using the median of individual changes in viraemia 1 month after initiation of ddI therapy. RESULTS: After 1 month of ddI, mean viraemia decreased by 0.35 log RNA copies/ml of serum (P < 0.001) in the population. A significant difference in survival (median, 14 and 35 months in nonresponders and responders, respectively; log rank, P = 0.004) and in the delay to the occurrence of new AIDS-defining events (median, 8 and 33 months in nonresponders and responders, respectively; log rank, P = 0.018) was observed. After stratification for presence of AIDS before starting ddI, viraemia response at 1 month remained predictive of both overall and AIDS-defining event-free survival (log rank, P = 0.0006 and P = 0.01). After a similar stratification for initial CD4, viraemia response still predicted overall survival (log rank, P = 0.009), but its predictive value for AIDS-defining event-free survival did not reach statistical significance (P = 0.12). High initial levels of HIV RNA, presence of mutation 215 or previous duration of zidovudine therapy were not predictive of survival. CONCLUSIONS: In patients treated with ddI, changes in viraemia at 1 month predict survival independently of initial AIDS diagnosis and initial CD4 counts.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Human immunodeficiency virus type 1 nucleic acids detected before p24 antigenemia in a blood donor.

A blood donation from a 46-year-old homosexual man was discarded because of elevated alanine aminotransferase levels. Thirteen days later, the patient presented with symptomatic primary human immunodeficiency virus type 1 (HIV-1) infection. Virologic investigations were performed retrospectively on blood samples (including the donated blood) obtained before the symptoms. The HIV-1 genome was present, either integrated in mononuclear cell DNA or circulating in plasma, 39 days before the appearance of p24 antigen and 65 days before the appearance of HIV-1 or HIV type 2 antibody. It is concluded that p24 antigenemia is present during only a fraction of the seronegative "window" period. This case illustrates the risk of infection associated with blood transfusion in spite of HIV-1 antibody testing and stresses the need to improve nontechnical exclusion procedures as well as non-antibody-based diagnostic tests.

Base Sequence↗
PubMed1993

High levels of circulating RNA in patients with symptomatic HIV-1 infection.

OBJECTIVE: To evaluate the concentration of circulating RNA (viraemia) in patients with symptomatic primary HIV infection and relate it to sero-immunological parameters. METHODS: Semiquantitation of circulating HIV RNA and proviral HIV DNA was performed using the polymerase chain reaction. Circulating HIV RNA concentrations were expressed as virus equivalent (RNA copies/2) per ml serum. RESULTS: The mean CD4+ lymphocyte count for 19 patients with symptomatic primary HIV infection was 583 x 10(6)/l. Fifteen (79%) patients had detectable levels of p24 antigen (median 462 pg/ml). Circulating HIV RNA (median 2.3 x 10(7) virus equivalent/ml serum) and proviral HIV DNA (median 3630 copies/ml blood) were detected in all samples tested. Follow-up data for five patients (200-1600 days) showed a 1-3 log reduction in circulating RNA within 2 months. Later, circulating RNA concentrations were consistently greater than 10(3) virus equivalent/ml serum. Within 10 days no p24 antigen was detectable. Levels of CD4+ cells varied markedly from patient to patient during the follow-up and, in this small group, no evident correlation was observed between circulating RNA levels and CD4+ lymphocyte counts. CONCLUSIONS: High concentrations of circulating RNA (viraemia) were present in 19 patients with symptomatic primary HIV infection. Although a decrease in viraemia was observed during the following 2 months, viraemia persisted in all patients with long-term follow-up. This suggests that active viral replication is a continuous process in HIV-infected patients.

Adult↗
PubMed1992

Quantitation of human immunodeficiency virus provirus and circulating virus: relationship with immunologic parameters.

Virologic and seroimmunologic parameters were determined in 56 persons infected with human immunodeficiency virus (HIV). The provirus level varied from 10 to 100,000/10(6) CD4+ lymphocytes, and genomic HIV RNA was detectable in 39 of 56 patients at a relative concentration varying from 10 to greater than 250 copies/mL of serum. Provirus expressed as copies per 10(6) CD4+ lymphocytes and as circulating virus per milliliter of serum increased with disease progression and decrease of CD4+ cell concentration. The mean provirus concentration expressed per milliliter of blood varied little among categories of patients with various levels of CD4+ cells, but there was a progressive increase of circulating HIV genomic RNA. These virologic data suggest that during the course of HIV infection, an increasing proportion of the remaining CD4+ lymphocytes harbor the HIV genome and produce infectious virus. Finally, there was a marked correlation between increased provirus and genomic RNA concentration and three seroimmunologic markers: decrease in CD4+ cell count, p24 antigenemia, and disappearance of antibodies to HIV core antigen.

Base Sequence↗
PubMed1991

Absence of chronic human immunodeficiency virus infection without seroconversion in intravenous drug users: a prospective and retrospective study.

It has been reported that human immunodeficiency virus type 1 (HIV-1) infection may exist in persons without specific antibodies for years. To measure the frequency of a silent carrier state, a study was conducted in a cohort of 124 intravenous drug users (IVDUs) without anti-HIV-1 antibodies. All the participants had engaged in high-risk behavior for HIV-1 transmission for a number of years until 1987 or later. Samples were analyzed at 6-month intervals for the presence of HIV-1 provirus using DNA amplification and for the appearance of anti-HIV-1 antibodies. HIV-1 provirus and antibodies were undetectable in 122 participants, whereas seroconversion was observed in 2. In one of these, both amplified HIV-1 pol gene segment and anti-HIV-1 antibodies were detected simultaneously, and in the other, provirus was detected 1 month before seroconversion. This study suggests that long-term HIV-1 infection without anti-HIV-1 antibodies is rare and that repeated antibody testing is sufficient to determine the HIV-1 status of a person no longer at high risk for HIV-1 infection.

Adult↗
PubMed1991

Comparative evaluation of an ELISA based on recombinant polypeptides and IFA for serology of malaria.

In the present investigation we compare the performance of a solid-phase assay based on three recombinant polypeptides corresponding to three asexual blood-stage antigens of P. falciparum (ELISA MIXT) with the reference method for the measurement of antimalaria antibodies: indirect immunofluorescence antibody assay (IFA). Sera collected from persons with various degrees of exposure to malaria were selected: sera from inhabitants of a malaria endemic area (Group I), European patients with acute malaria infection (Group II) and blood donors with clinical symptoms of sickness or fever during a stay in malaria endemic areas. 86% of the sera gave concording results by ELISA MIXT and IFA. The correlation was 100% for sera of Group I but discrepancies were observed for Groups II and III. The great majority of the differences were due to sera positive on ELISA MIXT but not by IFA. Most of the sera positive on ELISA MIXT reacted with parasite-derived components only on Western-blot. These results underline the potential of the ELISA MIXT for epidemiologic studies.

Adolescent↗
PubMed1990

Human immunodeficiency virus DNA amplification and serology in blood donors.

The significance of indeterminate screening antibody test for human immunodeficiency virus (HIV) serology is still difficult to evaluate, especially in low-risk populations. One hundred twenty-seven blood donors with an initially reactive screening test for HIV antibodies were enrolled in this study. The sera of 95 of these blood donors were reactive on repetition of the test, and none had detectable circulating p24 antigen. Western blot (WB) analysis of the repeatedly reactive sera was as follows: 9 positive, 31 indeterminate, and 55 negative. One of the blood donors with indeterminate WB later presented a seroconversion. On subsequent control 3 to 12 months later, the sera from donors with indeterminate or negative WB did not present any parameters that may indicate a seroconversion. DNA was purified from citrated blood collected from the 127 blood donors at the time of the initial antibody screening. Five micrograms of each DNA sample corresponding to 7 x 10(5) nucleated white blood cells was amplified by polymerase chain reaction (PCR) in the presence of oligonucleotides (primers) corresponding to a highly conserved segment of the pol gene. The detection of amplified DNA was achieved by dot blot and Southern blot using appropriate 32P-labeled oligonucleotides. Ten DNA samples were positive, 9 corresponded to blood donors with a positive HIV serology, and 1 to the blood donor who later presented a seroconversion. These results confirm the sensitivity of the PCR for the diagnosis of HIV infection; they also suggest that repetition of the serology at 3- to 12-month intervals is a valuable procedure for the control of HIV infection status in blood donors.

Base Sequence↗
PubMed1990

Development of a haptoglobin ELISA. Its use as an indicator for malaria.

Hypo- or ahaptoglobinemia, a common phenomenon in tropical countries, is mainly due to malaria induced hemolysis. We have recently shown that the prevalence of hypohaptoglobinemia is a useful epidemiologic indicator in malaria endemic areas. The main limitation to the practical utilisation of this indicator is the available methodologies. Here we describe a sandwich ELISA for the determination of haptoglobin concentrations which is easy to perform, sensitive and requires a minimal amount of equipment. With this test system it is possible to detect haptoglobin in serum at a lower limit of 100 micrograms/ml for 10(-4) dilutions and of less than 1 micrograms/ml for 10(-2) dilutions. This represents at least 200 fold increase in sensitivity as compared to radial immunodiffusion.

Enzyme-Linked Immunosorbent Assay↗