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Biomedical subjects

B Hirschel

Publications and source records attributed to B Hirschel.

At least 19 recordsLinked to original sources
PubMed1998

Antiretroviral therapies in pregnancy: maternal, fetal and neonatal effects. Swiss HIV Cohort Study, the Swiss Collaborative HIV and Pregnancy Study, and the Swiss Neonatal HIV Study.

BACKGROUND: Therapies containing two reverse transcriptase inhibitors (RTI) with or without protease inhibitors are used with increasing frequency in pregnant HIV-infected women. OBJECTIVE: To assess the safety of antiretroviral therapy in pregnant women and their newborns. METHODS: All clinical events and laboratory abnormalities in pregnant women on RTI with or without protease inhibitors and in their newborns were collected through an observational study. RESULTS: A total of 37 HIV-infected pregnant women have given birth to 30 children (by 30 April 1998). All received RTI, which were combined with protease inhibitors in 16 cases. Twelve women became pregnant while on treatment. Drugs used were as follows: zidovudine (n = 33), lamivudine (n = 33), stavudine (n = 4), indinavir (n = 9), ritonavir (n = 4), nelfinavir (n = 2) and saquinavir (n = 2). Adverse events during pregnancy were anaemia (n = 15), elevation of transaminases (n = 4), nausea/vomiting (n = 4), glucose intolerance (n = 2), nephrolithiasis (n = 2), diarrhoea (n = 2), hypertension (n = 1), insulin-requiring diabetes (n = 1). Adverse events in neonates were prematurity (n = 10), anaemia (n = 8), cutaneous angioma (n = 2), cryptorchidism (n = 2), transient hepatitis (n = 1). Non-life-threatening intracerebral haemorrhage occurred in a premature baby (33 weeks gestation) exposed during fetal life to zidovudine-lamivudine-indinavir, and in a term baby exposed to stavudine-lamivudine-indinavir. Extrahepatic biliary atresia occurred in one newborn exposed to zidovudine-lamivudine-indinavir. Maternal viral load was below 400 copies/ml in 18 out of 30 patients who delivered. One case of mother-to-child HIV transmission was identified. CONCLUSIONS: In HIV-infected pregnant women treated with two RTI with or without protease inhibitors, one or more adverse events occurred in 29 out of 37 women and in 14 out of 30 babies. In newborns, frequent prematurity, one case of biliary malformation and one intracerebral haemorrhage in a term baby are of concern. These observations do not preclude combination therapies during pregnancy but emphasize the necessity to maintain updated registers on their safety.

Anti-HIV Agents↗
PubMed1998

Prevalence and incidence rate of HIV, hepatitis B and C among drug users on methadone maintenance treatment in Geneva between 1988 and 1995.

OBJECTIVES: To evaluate the prevalence and incidence rates of infection with HIV, hepatitis B (HBV) and hepatitis C (HCV), in a cohort of drug users (DU) in Geneva, Switzerland. DESIGN: Prospective open cohort study. SETTING: Private methadone maintenance treatment (MMT) programme. PATIENTS, PARTICIPANTS: Over 700 DU in treatment between 1988 and 1995 were tested biannually for HIV, HBV and HCV infection. INTERVENTION: None. MAIN OUTCOME MEASURE: Prevalence for HIV, HBV and HCV at study entry, determined by gender, by injection behaviour, by year of start of MMT and incidence rates for HIV, HBV and HCV, assuming equal risk of seroconversion on each day of the interval between last negative and first positive test. RESULTS: The prevalence at entry into treatment declined dramatically over time for all three viruses. Comparing DU entering treatment before 1988 to those entering treatment after 1993, the prevalence of HIV was 38.2% versus 4.5%, of HBV 80.5% versus 20.1%, and of HCV 91.6% versus 29.8%, respectively. Follow-up rate was 80%. The incidence rates for HIV and HBV were 0.6% and 2.1% per person-year of follow-up, respectively. For HCV the rate was higher (4.2%) especially among women (9.6%). CONCLUSION: These data suggest that DU have changed HIV risk-taking behaviour in response to HIV prevention campaigns. Current prevention efforts should focus on improvement of HCV prevention, identification of high-risk individuals and maintaining safe behaviour.

Cohort Studies↗
PubMed1998

A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection. The Swiss HIV Cohort Study.

OBJECTIVE: To explore the short-term effects on surrogate markers for HIV progression of didanosine (ddl) plus stavudine (d4T), with or without hydroxyurea. DESIGN: Randomized, double-blinded, prospective study. SETTING: Swiss HIV Cohort Study. PATIENTS: A total of 144 patients (75% antiretroviral-naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell count, 370 x 10(6)/l). INTERVENTION: Patients received ddl (200 mg twice daily) plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or placebo. MAIN OUTCOME MEASURES: The primary endpoint was a reduction of viraemia below 200 copies/ml after 12 weeks. At that time, patients who did not reach the primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the placebo group had the option of adding hydroxyurea to ddl and d4T. All patients were followed until week 24. RESULTS: After 12 weeks, 54% of the patients randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of 20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20 copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was 2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P = 0.001). Hydroxyurea was found to induce lymphopenia (-124 x 10(6)/l). Increase in CD4 cell counts was +28 x 10(6)/l during hydroxyurea treatment compared with +107 x 10(6)/l on placebo (P = 0.001). CONCLUSIONS: Hydroxyurea improved the antiviral activity of d4T and ddl over a 12-week period, but was associated with a smaller increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.

Adult↗
PubMed1998

Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen.

We investigated CD4+ and CD8+ T cell turnover in both healthy and HIV-1-infected adults by measuring the nuclear antigen Ki-67 specific for cell proliferation. The mean growth fraction, corresponding to the expression of Ki-67, was 1.1% for CD4(+) T cells and 1.0% in CD8(+) T cells in healthy adults, and 6.5 and 4.3% in HIV-1-infected individuals, respectively. Analysis of CD45RA+ and CD45RO+ T cell subsets revealed a selective expansion of the CD8+ CD45RO+ subset in HIV-1-positive individuals. On the basis of the growth fraction, we derived the potential doubling time and the daily turnover of CD4+ and CD8+ T cells. In HIV-1-infected individuals, the mean potential doubling time of T cells was five times shorter than that of healthy adults. The mean daily turnover of CD4+ and CD8+ T cells in HIV-1-infected individuals was increased 2- and 6-fold, respectively, with more than 40-fold interindividual variation. In patients with <200 CD4+ counts, CD4+ turnover dropped markedly, whereas CD8+ turnover remained elevated. The large variations in CD4+ T cell turnover might be relevant to individual differences in disease progression.

Adult↗
PubMed1998

Survival in 2367 zidovudine-treated patients according to use of other nucleoside analogue drugs. The EuroSIDA Study Group.

To evaluate survival according to use of different nucleoside drugs in a routine clinical setting, we studied a large group of zidovudine-treated patients seen in clinics across Europe. A total of 3128 subjects was recruited to the observational, prospective EuroSIDA study in May 1994. These were consecutive patients (up to a predefined limit) seen at outpatient clinics in 37 centers from 16 European countries and followed at 6-month intervals by use of standardized forms completed by clinicians at the respective centers. This report concerns 2367 subjects who began antiretroviral therapy with a regime that included zidovudine either before study entry or during the course of follow-up. Cox proportional hazards models were fitted, with use of other antiretroviral drugs, CD4 count, and date of development of AIDS fitted as time-dependent covariates. Survival times from start of therapy were left truncated at study entry to avoid survival bias. In addition to zidovudine, antiretroviral drugs used included didanosine (ddI) (n = 1119; median 1.6 years after starting zidovudine), dideoxycytidine (ddC) (n = 592; median 1.9 years after starting zidovudine), stavudine (d4T) (n = 241; median 2.9 years after starting zidovudine) and lamivudine (3TC) (n = 33 ; median 2.7 years after starting zidovudine). Of the 2367 patients, 613 died during follow-up. Overall, risk of death was reduced in those zidovudine-treated patients who began at least one other nucleoside analogue drug with or after taking zidovudine (relative hazard [RH], 0.61; 95% confidence interval [CI], 0.51-0.72, adjusting for CD4 count, development of AIDS, and age). Fitting each drug separately, there was a larger association with reduced mortality for starting 3TC (RH, 0.41; 95% CI, 0.28-0.62) than for starting ddl (RH, 0.79; 95% CI, 0.67-0.93), ddC (RH, 0.74; 95% CI, 0.59-0.92) or d4T (RH, 0.67; 95% CI, 0.49-0.91). These results suggest that the beneficial effect of nucleoside combination therapy identified in controlled trials can be seen in routine clinical practice.

Adult↗
PubMed1998

A critical assessment of the prognostic value of HIV-1 RNA levels and CD4+ cell counts in HIV-infected patients. The Swiss HIV Cohort Study.

OBJECTIVE: To determine to what extent human immunodeficiency type 1 (HIV-1) RNA levels and CD4+ cell counts predict clinical outcomes in a general HIV-1-infected population. METHODS: Community-based prospective study (Swiss HIV Cohort Study) including 394 HIV-1-infected patients, randomly selected from 4 strata of CD4+ cell counts (0 to < 0.05, 0.05 to < 0.20, 0.20 to < 0.50, and > or = 0.50 x 10(9)/L). Levels of HIV-1 RNA, CD4+ cell counts, and other variables were evaluated from samples collected between 1991 and 1993 for their ability to predict death and clinical progression. RESULTS: Patients were followed up on average for 29 months. Baseline HIV-1 RNA levels, CD4+ cell counts, clinical stage, and beta 2-microglobulin levels independently predicted survival, whereas only HIV-1 RNA levels and CD4+ cell counts independently predicted clinical progression. Multivariate relative hazards (RHs) for death ranged from 1.0 to 5.4 across quartiles of CD4+ counts, but only from 1.0 to 1.8 across quartiles of HIV-1 RNA. For clinical progression, gradients of risk were similar for CD4+ counts (1.0-4.2) and for HIV-1 RNA (1.0-3.1). In patients with CD4+ cell counts less than 0.05 x 10(9)L, HIV-1 RNA levels predicted neither death nor clinical progression. Finally, the number of HIV-1 RNA copies per CD4+ cell was the best predictor of death (multivariate RH, 1.0-9.7 across quartiles) and clinical progression (multivariate RH, 1.0-4.1). CONCLUSIONS: Levels of HIV-1 RNA and CD4+ cell counts provided independent and complementary information on clinical outcomes. The RNA/CD4+ ratio was the best single predictor. In patients who had fewer than 0.05 x 10(9)/L CD4+ cells, HIV-1 RNA levels had little prognostic value.

Adult↗
PubMed1998

A randomized double-blind controlled study of 6 months of oral nutritional supplementation with arginine and omega-3 fatty acids in HIV-infected patients. Swiss HIV Cohort Study.

OBJECTIVE: To evaluate the effects of an oral nutritional supplement enriched with two potentially immunostimulant compounds (arginine and omega-3 fatty acids) on the changes in food intake, body composition, immune parameters and viraemia in HIV-infected outpatients. DESIGN: Six-month prospective randomized double-blind controlled study. SETTING: University hospital outpatient nutrition clinic. PATIENTS: Sixty-four HIV-infected outpatients with CD4 lymphocyte count > or = 10O x 10(6)/l. INTERVENTION: All patients received a daily oral nutritional supplement (606 kcal supplemented with vitamins, trace elements and minerals). In addition, half of the patients were randomized to receive 7.4 g arginine plus 1.7 g omega-3 fatty acids. MAIN OUTCOME MEASURES: Disease progression measured by AIDS-defining events, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors, nutritional status determined by anthropometric, bioelectrical impedance and dietetic assessment. RESULTS: Fifty-five patients completed the protocol. Compliance with and tolerance of oral nutritional supplement during the 6-month period was excellent. In both groups of patients the following were found: total energy intake was transiently increased and then returned to baseline level; nitrogen/energy intake ratio was increased throughout the study; gain of body weight and fat mass were approximately 2 and 1kg, respectively, over 6 months, and were similar in both groups. In addition, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors remained statistically unchanged and were similar in both groups. CONCLUSIONS: Enrichment of an oral nutritive supplement with arginine and omega-3 fatty acids did not improve immunological parameters. However, body weight increased in both groups.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Colour vision in AIDS patients without HIV retinopathy.

Patients suffering from AIDS develop ocular complications, the most frequent being HIV retinopathy. It is however not clear, if functional visual impairments can be observed as early indicators of ocular complications, before clinical diagnosis of HIV retinopathy is made at fundus examination. To address this issue, we measured colour vision in a group of 49 AIDS subjects with normal clinical fundi using the 'two equation method'. This method, combining red-green Rayleigh and the blue-green Moreland metameric matches, enables more complete and quantitative assessments of colour vision than those based on pigmentary tests. Data were collected on our computer controlled colorimeter and compared to those of normal subjects. While most AIDS subjects without HIV retinopathy demonstrated normal colour vision, a significant portion of them had wider matches than normal subjects (11% for the Rayleigh equation and 16% for the Moreland equation). Furthermore, matching ranges of the Moreland equation were significantly correlated with CD4 lymphocyte counts. Patients with low CD4 values tended to produce larger matching ranges than the patients with high CD4 values. A within subject study on 17 patients confirmed this trend and showed that the patients who increased/decreased their CD4 blood counts generally improved/impaired their colour discrimination in the Moreland match. No such correlation was found between the matching ranges of the Rayleigh equation and the CD4 counts. These results show that colour discrimination is slightly reduced in some AIDS subjects, although there are no detectable ocular complications. They also suggest two different types of colour vision impairments in AIDS patients without retinopathy: one reversible process affecting colour discrimination in the blue-green range; and another irreversible process affecting colour discrimination in the red-green range.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Regression of Kaposi's sarcoma during therapy with HIV-1 protease inhibitors: a prospective pilot study.

BACKGROUND: Early studies using HIV protease inhibitors (PI) showed regression of Kaposi's sarcoma (KS) lesions in some patients. OBJECTIVE: Our purpose was to determine prospectively the influence of PI on HIV-related KS. METHODS: KS lesions of nine patients with progressive cutaneous disease were prospectively evaluated clinically and by means of epiluminescence microscopy before and during PI therapy. HIV viremia and CD4 cell count were measured in parallel. RESULTS: All patients experienced reduction or initial stabilization of KS lesions during the first 4 to 8 weeks of HIV-1 PI therapy. After a median follow-up of 7 months and according to AIDS Clinical Trials Groups criteria, six patients had a partial response, two showed stable disease, and in one noncompliant patient KS progressed, requiring chemotherapy. With epiluminescence microscopy, a reduction in skin surface alterations, lesional size, and color intensity was demonstrated in six of nine patients. PI induced a median decrease in viremia of 1.66 log and a median increase in the CD4 count of 49 cells/mm3. CONCLUSION: In this series, HIV PI therapy reduced or stabilized KS. The efficacy of HIV-1 PI in KS may result from the improvement in cellular immunity. These results suggest the use of PI in AIDS-related KS regardless of the level of CD4 lymphocyte count and HIV viremia.

CD4 Lymphocyte Count↗
PubMed1998

Virus burden in lymph nodes and blood of subjects with primary human immunodeficiency virus type 1 infection on bitherapy.

At present, it is not known whether undetectable plasma viremia corresponds to an absence of human immunodeficiency virus type 1 (HIV-1) replication in lymphoid tissues. This issue has been explored in 11 subjects with primary HIV-1 infection treated with zidovudine plus didanosine by evaluating virologic markers in blood and lymphoid tissues 9-18 months after initiation of treatment. These markers include plasma viremia, measured with a sensitive assay with a detection limit of 20 HIV-1 RNA copies/mL, infectious virus titers and proviral DNA in lymph node mononuclear cells, and HIV-1 RNA in lymphoid tissue. Five subjects had plasma viremia <20 copies/mL and showed no evidence of viral replication in lymphoid tissue. Six subjects had both detectable plasma viremia and evidence of HIV-1 RNA in lymphoid tissue. The results indicate that absence of detectable HIV RNA in lymphoid tissue is associated with viremia levels of HIV-1 RNA <20 copies/mL.

Adenoids↗
PubMed1998

Severity and prognosis of acute human immunodeficiency virus type 1 illness: a dose-response relationship.

This study examined the relationship between the severity of acute human immunodeficiency virus type 1 (HIV-1) illness and disease progression and death. The population included 218 patients with acute HIV-1 illness and 41 asymptomatic patients who underwent HIV-1 seroconversion; the patients were followed up prospectively. We analyzed progression to Centers for Disease Control and Prevention clinical categories B and C (AIDS-defining conditions) and death according to an additive clinical score (CS) based on six predictive clinical features at the time of acute HIV-1 infection. Compared with patients with a CS of 0 (asymptomatic patients), those with a CS of 3-4 and 5-6 had faster progression to category B disease (adjusted hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.01-1.92; and HR, 1.80; 95% CI, 1.34-2.40; respectively); those with a CS of 5-6 had faster progression to category C disease (HR, 1.37; 95% CI, 1.01-1.89) and death (HR, 2.05; 95% CI, 1.27-3.32). Thus, the number of symptoms and signs at the time of acute HIV-1 illness affects disease progression and survival, even in symptomatic patients who have undergone seroconversion.

Acute Disease↗
PubMed1998

Impact of treatment with human immunodeficiency virus (HIV) protease inhibitors on hepatitis C viremia in patients coinfected with HIV.

The impact of human immunodeficiency virus (HIV) protease inhibitors on hepatitis C (HCV) viremia was assessed in 19 patients infected with both HIV and HCV. HIV and HCV RNA levels were measured before and during treatment with protease inhibitors. Before treatment, mean levels of HCV RNA were 5.3 log for HCV RNA and 5.0 log for HIV RNA. CD4 lymphocyte counts were 63/mm3. After 6 weeks of treatment, a mean reduction of 2.1 log10 in HIV RNA (P < .001) and a mean (+/-SE) increase of 73 (+/-21) CD4 and 296 (+/-70) CD8 cells were observed (P < .05). In contrast, both HCV viremia (+0.4 log +/- 0.1) and alanine aminotransferase increased (P < .04). HCV RNA levels returned to baseline after 17 and 32 weeks of treatment. Thus, potent anti-HIV regimens with protease inhibitors may temporarily worsen HCV status despite improvement of HIV parameters.

Anti-HIV Agents↗
PubMed1998

16S rRNA sequence diversity in Mycobacterium celatum strains caused by presence of two different copies of 16S rRNA gene.

Direct sequencing of the 16S rRNA gene (16S rDNA) of Mycobacterium celatum isolates showed ambiguities, suggesting heterogeneity. Cloned 16S rDNA yielded two copies of the gene, which differed by insertion of a thymine at position 214 and by additional mismatches. Restriction fragment length polymorphism analysis confirmed the presence of two copies of 16S rDNA within the bacterial chromosome.

Base Sequence↗
PubMed1998

Microaerophilic conditions promote growth of Mycobacterium genavense.

Our studies show that microaerophilic conditions promote the growth of Mycobacterium genavense in semisolid medium. The growth of M. genavense at 2.5 or 5% oxygen was superior to that obtained at 21% oxygen in BACTEC primary cultures (Middlebrook 7H12, pH 6.0, without additives). By using nondecontaminated specimens, it was possible to detect growth with very small inocula (25 bacilli/ml) of 12 different M. genavense strains (from nude mice) within 6 weeks of incubation under low oxygen tension; conversely, with 21% oxygen, no growth of 8 of 12 (66.7%) M. genavense strains was detected (growth index, <10). The same beneficial effect of 2.5 or 5% oxygen was observed in primary cultures of a decontaminated clinical specimen. Low oxygen tension (2.5 or 5%) is recommended for the primary isolation of M. genavense. Microaerophilic cultivation of other atypical mycobacteria, especially slow-growing (e.g., Mycobacterium avium) and difficult-to-grow (e.g., Mycobacterium ulcerans) species, is discussed.

AIDS-Related Opportunistic Infections↗
PubMed1998

Switch to unusual amino acids at codon 215 of the human immunodeficiency virus type 1 reverse transcriptase gene in seroconvertors infected with zidovudine-resistant variants.

Sequences of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) domain were determined by direct sequencing of HIV-1 RNA in successive plasma samples from eight seroconverting patients infected with virus bearing the T215Y/F amino acid substitution associated with zidovudine (ZDV) resistance. At baseline, additional mutations associated with ZDV resistance were detected. Three patients had the M41L amino acid change, which persisted. Two patients had both the D67N and the K70R amino acid substitutions; reversion to the wild type was seen at both positions in one of these patients and at codon 70 in the other one. Reversion to the wild type at codon 215 was observed in only one of eight patients. Unusual amino acids, such as aspartic acid (D) and cysteine (C), appeared at position 215 in four patients during follow-up. These variants isolated by coculturing were sensitive to ZDV. Overgrowth of these variants suggests that they have better fitness than the original T215Y variant. Intraindividual nucleoside substitutions over time were 10 times more frequent in codons associated with ZDV resistance (41, 67, 70, 215, and 219) than in other codons of the RT domain. The predominance of nonsynonymous substitutions observed over time suggests that most changes reflect adaptation of the RT function. The variance in sequence evolution observed among patients, in particular at codon 215, supports a role for chance in the evolution of the RT domain.

Amino Acids↗
PubMed1997

Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study.

OBJECTIVES: To examine trends in disease progression and survival among patients enrolled in the Swiss HIV cohort study during 1988-96 and to assess the influence of new antiretroviral combination therapies. DESIGN: Prospective multicentre study, with follow up visits planned at six monthly intervals. SETTING: Seven HIV units at university centres and cantonal hospitals in Switzerland. PATIENTS: 3785 men (mean age 35.0 years) and 1391 women (30.3 years) infected with HIV. 2023 participants had a history of intravenous drug misuse; 1764 were men who had sex with men; 1261 were infected heterosexually; and 164 had other or unknown modes of transmission. 601 participants had had an AIDS defining illness. RESULTS: During more than 15,000 years of follow up, there were 1456 first AIDS defining diagnoses and 1903 deaths. Compared with those enrolled during 1988-90, the risk of progression to a first AIDS diagnosis was reduced by 18% (relative risk 0.82 (95% confidence interval 0.73 to 0.93)) among participants enrolled in 1991-2, by 23% (0.77 (0.65 to 0.91)) among those enrolled in 1993-4, and by 73% (0.27 (0.18 to 0.39)) among those enrolled in 1995-6. Mortality was reduced by 19% (0.81 (0.73 to 0.90)), 26% (0.74 (0.63 to 0.87)), and 62% (0.38 (0.25 to 0.97)) respectively. Compared with no antiretroviral treatment, the risk of an initial AIDS diagnosis after CD4 lymphocyte counts fell to < 200 cells x 10(6)/1 was reduced by 16% (0.84 (0.73 to 0.97)) with monotherapy, 24% (0.76 (0.63 to 0.91)) with dual therapy, and 42% (0.58 (0.37 to 0.92)) with triple therapy. Mortality was reduced by 23% (0.77 (0.68 to 0.88)), 31% (0.69 (0.60 to 0.80)), and 65% (0.35 (0.20 to 0.60)) respectively. CONCLUSIONS: The introduction of antiretroviral combination therapies outside the selected patient groups included in clinical trials has led to comparable reductions in disease progression and mortality.

Acquired Immunodeficiency Syndrome↗