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G J Weverling

Publications and source records attributed to G J Weverling.

At least 55 records · Page 3Linked to original sources
PubMed1998

Seroconversion for human herpesvirus 8 during HIV infection is highly predictive of Kaposi's sarcoma.

BACKGROUND: The finding of antibodies against human herpesvirus 8 (HHV-8) is associated with the occurrence of Kaposi's sarcoma in persons infected with HIV. However, the predictive value of HHV-8 antibodies for Kaposi's sarcoma in HIV infection is unknown. METHODS: The Amsterdam Cohort Studies on HIV infection and AIDS started in 1984 for homosexual men and in 1985 for injecting drug users. Serum samples from 1459 homosexual men and 1167 drug users were tested for antibodies to recombinant HHV-8 lytic-phase capsid (ORF65) antigen and latent-phase nuclear (ORF73) antigen. Individuals were retrospectively identified as HHV-8-positive or HHV-8-negative at enrolment or HHV-8 seroconverter during the study. Kaposi's sarcoma-free survival time was compared between HIV-infected men who were positive for HHV-8 at enrolment and those who later seroconverted for HHV-8. Hazard ratios were estimated for Kaposi's sarcoma, lymphoma, and opportunistic infection according to the HHV-8 serostatus. RESULTS: The incidence of HHV-8 seroconversion among drugs users was 0.7 per 100 person-years based on 31 seroconversions, whereas an incidence of 3.6 was found among homosexual men based on 215 seroconversions. The hazard ratio for Kaposi's sarcoma was 3.15 (95% CI: 1.89-5.25) in HIV-infected individuals if HHV-8 antibodies were present either at enrolment or at HIV seroconversion. In HIV-infected persons who later seroconverted to HHV-8, Kaposi's sarcoma developed more rapidly: hazard ratio of 5.04 (95% CI: 2.94-8.64), an additional risk of 1.60 (95% CI: 1.01-2.53; P = 0.04). Time-dependent adjustment for CD4+ cell count and HIV RNA had no impact on the additional risk, although the CD4+ cell count was an independent risk factor for Kaposi's sarcoma. HHV-8 infection did not increase the risk of AIDS-related lymphoma or opportunistic infections. CONCLUSIONS: The incidence of HHV-8 infection is higher in homosexual men than in drug users. The presence of HHV-8 antibodies in HIV-infected persons increases the risk of Kaposi's sarcoma. Among HIV-infected persons, those who subsequently seroconvert for HHV-8 are at highest risk. These results strongly confirm the causal role of HHV-8 in Kaposi's sarcoma and emphasize the clinical relevance of HHV-8 seroconversion before and after the HIV infection.

Adult↗
PubMed1998

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. In this arm the differences from baseline for both HIV-1 RNA load and CD4+ T cell counts were small and transient. In both combination therapy arms, the maximum mean decline in HIV-1 DNA load was 0.6 log and it never differed significantly from baseline. This is in contrast to plasma HIV-1 RNA load that declined earlier and steeper (mean of 1.5 and 1.9 log for AZT + ddC and AZT + ddI, respectively) and that remained significantly below baseline for 80 weeks. Although 9 of 42 (32%) of the patients under combination therapy had prolonged decreased plasma RNA levels, the proviral HIV-1 DNA remained present in the cells throughout the total follow-up of 144 weeks. In conclusion, combination therapy showed better laboratory parameter responses than AZT monotherapy, in agreement with the clinical data. The HIV-1 DNA sequences did not disappear in any of the patients, heralding renewed active infection after cessation of therapy.

Anti-HIV Agents↗
PubMed1998

The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy.

OBJECTIVE: To investigate the relationship between exposure to antiretroviral drugs and the initial decline of plasma HIV-1 RNA. DESIGN: Open-label study in antiretroviral-naive HIV-1 infected patients using a quadruple drug regimen [nelfinavir (NFV), saquinavir (SQV), stavudine, and lamivudine]. METHODS: The elimination rate constant (k) for HIV-1 clearance was calculated during the first 2 weeks of treatment in 29 patients. Exposure to NFV and SQV was quantified on each study visit. Observed NFV and SQV concentrations were related to those expected in a reference population and a concentration ratio was calculated. The median concentration ratios for NFV and SQV, the baseline CD4+ lymphocyte count and baseline log10 HIV-1 RNA were correlated with k. RESULTS: A significant positive correlation was observed between k and the median NFV (P = 0.001) or SQV concentration ratio (P = 0.016) in univariate analysis. In multivariate analyses, the median NFV concentration ratio remained significantly correlated with k. CONCLUSIONS: The variation in the rate of decline of plasma HIV-1 RNA between patients after the initiation of a quadruple drug regimen could be explained by differences in exposure to NFV or SQV. Determination of k could be used to optimise further antiretroviral drug therapy and may be a first tool to assess antiretroviral activities of new or increasing doses of drugs administered in combination regimens. Furthermore, our data suggest that exposure to antiretroviral drugs should be incorporated in mathematical models to describe HIV-1 dynamics in more detail.

Anti-HIV Agents↗
PubMed1998

Alternative multidrug regimen provides improved suppression of HIV-1 replication over triple therapy.

OBJECTIVE: To compare the viral suppression of two antiretroviral regimens using three drugs or five drugs. DESIGN: Two open-label studies using a three-drug (zidovudine, lamivudine and ritonavir) and a five-drug regimen (zidovudine, lamivudine, abacavir, indinavir and nevirapine) in study-drug-naive patients, except for one in the five-drug study. METHODS: Participants with > or = 10 000 HIV-1 RNA copies/ml in plasma at baseline were compared by means of Kaplan-Meier curves for time to < 50 copies/ml, as well as linear regression analysis for the first phase of decline using log-transformed copy numbers. RESULTS: The elimination rate constants for HIV-1 RNA in 15 participants of the three-drug study were compared with nine participants of the five-drug study. The level of < 50 copies/ml was reached earlier when using the five-drug than when using the three-drug regimen (P log rank = 0.0005): median time to reach this level was 4 weeks and 12 weeks, respectively. No differences were found in HIV-1 RNA elimination rate constants in the first 2 weeks after the initiation of therapy. When the viral load declines were calculated from day 2 onwards, adjusting for differences in pharmacological delay of the drugs used, again no differences in early viral load decline were found between the two regimens. CONCLUSION: With the five drugs used in this study, the median time to reach < 50 HIV-1 RNA copies/ml was 8 weeks shorter than with the three-drug regimen. This finding shows that suppression of viral load in HIV-infection by standard triple-drug therapy can be improved upon.

Adult↗
PubMed1998

Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) study.

BACKGROUND: Highly active antiretroviral therapy (HAART) has led to health benefits for patients infected with HIV-1. However, long-term use of multidrug regimens is difficult to sustain. Simplifying antiretroviral treatment regimens would increase patients' adherence and minimise toxicity. We investigated the feasibility of a strategy of induction therapy followed by maintenance therapy with HAART in a randomised open-label study. METHODS: From March, 1997, we enrolled patients infected with HIV-1 with at least 200 CD4 cells/microL, at least 1000 HIV-1 RNA copies/mL in plasma, and no previous exposure to antiretroviral drugs. After 26 weeks of induction therapy (stavudine, lamivudine, saquinavir, and nelfinavir) patients were randomly allocated maintenance therapy (either stavudine and nelfinavir or saquinivir and nelfinavir) or prolonged induction therapy (if the plasma HIV-1 RNA concentration at weeks 24 and 25 was <50 copies/mL). FINDINGS: In February, 1998, we discontinued randomisation after an interim analysis. 62 patients had been enrolled. 39 (91%) of the 43 patients who were followed up for at least 26 weeks had an undetectable plasma HIV-1 RNA concentration at week 16. At week 26, 31 patients were randomly allocated treatment. Of these patients 25 had a total follow-up of at least 36 weeks. At week 36, a higher proportion of patients on maintenance therapy (nine [64%] of 14) had a detectable HIV-1 RNA than patients on prolonged induction therapy (one [9%] of 11, p=0.01). The initial virion-clearance rate during induction therapy was higher in five patients on maintenance therapy with a sustained undetectable plasma HIV-1 RNA concentration than in nine patients with recurrence of a detectable plasma HIV-1 RNA concentration at week 36 (0.35 vs 0.19 per day, respectively; p=0.0008). INTERPRETATION: The induction regimen provided a rapid suppression of viral replication to below 50 copies/mL. However, suppression was not sustained in a considerable number of patients who went onto maintenance therapy. It is currently inadvisable to continue attempts at moving from induction to maintenance therapy in day-to-day practice.

Adult↗
PubMed1998

Improvement of chronic diarrhoea in patients with advanced HIV-1 infection during potent antiretroviral therapy.

BACKGROUND: A substantial number of patients with advanced HIV infection suffer from intractable diarrhoea. The aim of this study was to evaluate whether potent antiretroviral therapy could alleviate such diarrhoea. METHODS: In an open randomized study the effect of the HIV protease inhibitor indinavir in combination with nucleoside analogue reverse transcriptase inhibitors on chronic HIV-related diarrhoea was investigated in 14 late-stage (CD4+ lymphocyte count < or = 50 x 10(6) cells/l) HIV-infected patients. Data concerning stool frequency, stool consistency and antidiarrhoeal drug use were collected in daily diaries over a 24-week period. Endpoints of the study were reduction of stool frequency, improvement of stool consistency, weight gain, and in case of diarrhoea due to Enterocytozoon bieneusi or Cryptosporidium sp. disappearance of these parasites from stool. RESULTS: Thirteen patients started the study drug indinavir. One patient died after 1 week and one patient withdrew prematurely after 18 weeks. Median stool frequency declined from 5.8 daily at baseline to 2.3 daily after 24 weeks (P=0.04). Stool consistency improved considerably over the study period: before treatment 56% of stools were watery and 0% were formed; at week 24 these figures were 0 and 35%, respectively. Body weight increased significantly with a median increment of 6.6 kg at week 24 (P=0.0006). In two out of six patients with microsporidiosis and both patients with cryptosporidiosis, stools were free of parasites at week 24. Five out of six patients who used non-specific antidiarrhoeal medication on a regular basis prior to the study had ceased to do so at the end. CONCLUSION: The use of potent antiretroviral therapy in patients with advanced HIV infection can improve chronic HIV-related diarrhoea and in some cases lead to disappearance of E. bieneusi and Cryptosporidium sp. from the stools.

AIDS-Related Opportunistic Infections↗
PubMed1997

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). Viral load in peripheral-blood mononuclear cells and plasma was measured by quantitative culture. Plasma HIV-1 RNA was measured by reverse-transcriptase PCR amplification, and serum p24 antigen by ELISA. Resistance to antiretroviral drugs was measured phenotypically by culture and genotypically by detection and quantification of drug-related point mutations in the pol gene. Analyses were done by intention to treat. FINDINGS: The reduction in viral load was greatest 4-12 weeks after the start of therapy and was most pronounced in the combination-therapy study groups (median reductions of RNA at 4 weeks 1.58, 1.28, and 0.49 log10 copies/mL for zidovudine plus didanosine, zidovudine plus zalcitabine, and zidovudine only, respectively). RNA levels at 8 weeks were predictive of disease progression and death after allowance for baseline values. At 48 weeks, the proportion of participants with phenotypic zidovudine resistance was similar in all three groups: didanosine and zalcitabine resistance were rare; zidovudine genomic resistance correlated with phenotypic resistance (r = 0.54, p < 0.0001) and developed earlier in the combined-therapy groups. However, participants in the zidovudine monotherapy group had higher circulating loads of resistant virus than those in the combined-therapy groups. INTERPRETATION: Combined antiretroviral therapy was more efficient at lowering virus load than monotherapy. Although zidovudine resistance was common in monotherapy and combined-therapy groups, circulating concentrations of resistant virus were substantially lower in the combination groups, which is likely to be a result of the continued antiviral activity of didanosine or zalcitabine.

Anti-HIV Agents↗
PubMed1997

Circadian variations in serum levels and the renal toxicity of aminoglycosides in patients.

Animals show a faster clearance and a lower incidence of nephrotoxicity and ototoxicity when aminoglycosides are administered during the activity period. Human data on a circadian rhythm in pharmacokinetics are conflicting, and there are no data on a circadian rhythm in toxicity. When aminoglycosides are administered once daily, as is often done, a circadian rhythm in pharmacokinetics or toxicity could have clinical implications. In a prospective study we investigated the influence of drug administration time on serum drug levels and the incidence of nephrotoxicity in 221 patients with serious infections treated with gentamicin or tobramycin once daily. We did not find statistically significant differences in trough or peak levels for the three time periods (midnight to 7:30 AM, 8 AM to 3:30 PM, and 4 to 11:30 PM). Nephrotoxicity occurred significantly more frequently when the aminoglycosides were administered during the rest period (midnight to 7:30 AM; p = 0.004). In addition to the coadministration of high-dose furosemide or other nephrotoxic antibiotics and the duration of treatment, the time of administration was still an independent risk factor in a multivariate analysis.

Adolescent↗
PubMed1997

Amyotrophic lateral sclerosis: mortality risk during the course of the disease and prognostic factors. The Netherlands ALS Consortium.

We performed a historical cohort study of 307 untreated patients with probable or definite amyotrophic lateral sclerosis in order to investigate whether the mortality risk changed during the disease course and to identify prognostic factors at diagnosis. Patients were diagnosed in one of the academic hospitals in The Netherlands and followed-up for at least 6 years after diagnosis. The median survival from diagnosis was 1.4 years (95% confidence interval, 1.3-1.6 years) with an estimated 5- and 10-year survival of 20 and 8%, respectively. Mortality was at its maximum in the second year after diagnosis and declined considerably thereafter. Observed mortality approached the expected mortality in patients who survived diagnosis 6 or more years. In univariate and multivariate analyses, young age, limb onset, and a long delay between initial weakness and diagnosis were associated with lower mortality. The better prognosis of limb-onset patients was not observed in females. Patients with initial respiratory muscle weakness, had the worst prognosis with a median survival of only 2 months. The significantly greater mortality of older patients proved not to result from a rise in expected mortality only. In conclusion, the annual mortality risk in ALS does not remain constant throughout the disease and depends on age at diagnosis, site of onset, diagnostic delay, but also on the time since diagnosis. These findings may have consequences for the planning of symptomatic care and the design and analysis of therapeutic trials.

Age Factors↗
PubMed1997

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. Rash was the most frequently reported adverse event, occurring in 25%. While sustained declines in p24 antigen levels were observed in the majority, serum HIV-1 RNA load and CD4 cell counts returned to baseline values within 12 weeks in virtually all subjects. The resistance-conferring tyrosine-to-cysteine substitution at reverse transcriptase position 181 was detected after 4 weeks in most subjects. These observations suggest that plasma drug levels attained with high-dose nevirapine were not sufficient to inhibit nevirapine-resistant virus, although they were approximately 2-fold higher than reported IC50 values of resistant virus.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Predictive value for survival of soluble tumor necrosis factor receptors p55 and p75 during zidovudine-containing treatment in symptomatic human immunodeficiency virus type 1 infection.

Previous studies of asymptomatic human immunodeficiency virus (HIV) infection have shown that serum levels of soluble tumor necrosis factor receptors (sTNFR) are good predictors of disease progression and clinical outcome during zidovudine (ZDV) therapy. The present study of symptomatic HIV infection was designed to evaluate whether sTNFR p55 and p75 at weeks 0 (pretreatment) and 24 and 48 are predictors of death < or = 3 years after the start of ZDV 1,000 mg alone or combined with low-dose interferon-alpha (ZDV 500 mg + IFN-alpha 3 MIU three times weekly). CD4+ T-cell numbers and serum neopterin were analyzed in a similar way. Forty previously untreated symptomatic HIV-infected persons with CD4+ T-cell numbers > or = 150 x 10(6)/L were included. At baseline, in the nonsurvivor group, mean age (42.1 vs. 34.4 years, p = 0.002) and neopterin (24.7 vs. 18.0 nmol/L, p = 0.02) were higher, whereas mean CD4+ T-cell counts (202 vs. 295 x 10(6)/L, p = 0.02) were lower than in the survivors. All analyses were adjusted for age. For the pretreatment marker values, a significant relative risk (RR) for death was noted only in the univariate analysis for sTNFR-p55 > 1.7 ng/ml [RR 3.1; 95% confidence interval (CI) 1.1-8.8; p = 0.04]. During therapy, CD4+ counts < 200 x 10(6)/L at week 24 and 48 and neopterin > 20 nmol/ml at week 48 were independent predictors of survival in the uni- and multivariate analysis. Marker values relative to baseline were not predictive. sTNFR-p55 and p75 were of little use as surrogate markers for clinical efficacy during ZDV-containing drug regimens in symptomatic HIV-infected patients with CD4+ counts 150 x 10(6)/L.

Adult↗
PubMed1996

[Computer-assisted education in problem-solving in neurology; a randomized educational study].

OBJECTIVE: To determine the effect of computer-based medical teaching (CBMT) as a supplementary method to teach clinical problem-solving during the clerkship in neurology. DESIGN: Randomized controlled blinded study. SETTING: Academic Medical Centre, Amsterdam, the Netherlands. METHOD: 103 Students were assigned at random to a group with access to CBMT and a control group. CBMT consisted of 20 computer-simulated patients with neurological diseases, and was permanently available during five weeks to students in the CBMT group. The ability to recognize and solve neurological problems was assessed with two free-response tests, scored by two blinded observers. RESULTS: The CBMT students scored significantly better on the test related to the CBMT cases (mean score 7.5 on a zero to 10 point scale; control group 6.2; p < 0.001). There was no significant difference on the control test not related to the problems practised with CBMT. CONCLUSION: CBMT can be an effective method for teaching clinical problem-solving, when used as a supplementary teaching facility during a clinical clerkship. The increased ability to solve problems learned by CBMT had no demonstrable effect on the performance with other neurological problems.

Computer-Assisted Instruction↗
PubMed1996

Validation and nephrotoxicity of a simplified once-daily aminoglycoside dosing schedule and guidelines for monitoring therapy.

There is no established dosing schedule for once-daily aminoglycoside dosing regimens, and accepted guidelines for monitoring therapy are lacking. We derived a simplified schedule from the Hull and Sarubbi (J. H. Hull and F. A. Sarubbi, Ann. Intern. Med. 85:183-189, 1976) nomogram, for which efficacy and safety in a once-daily dosing regimen were previously demonstrated, and prospectively followed serum aminoglycoside levels in patients. The standard treatment was gentamicin or tobramycin at 4 mg/kg of body weight given intravenously once daily. When the renal function was decreased, the daily dose was reduced, as follows: for an estimated creatinine clearance of between 50 and 80 ml/min, the daily dose was 3.25 mg/kg, for an estimated creatinine clearance of between 30 and 50 ml/min, the daily dose was 2.5 mg/kg, and for an estimated creatinine clearance of below 30 ml/min, the daily dose was 2 mg/kg. A total of 221 patients were studied (184 received gentamicin and 37 received tobramycin). First trough levels above 2 mg/liter were recorded in 11% of the patients, and they all had a baseline creatinine clearance below 50 ml/min, or a substantial decrease in clearance between enrollment and the day that the trough level was obtained. A peak level below 6 mg/liter was recorded in 6% of the patients, and half of them received the lowest daily dose. Twenty-five of the 179 evaluable patients (14%; 95% confidence interval, 9 to 19%) fulfilled the criteria for nephrotoxicity. In a multiple regression analysis, the duration of treatment and the use of other nephrotoxic antibiotics or high-dose furosemide, but not trough levels, were significant risk factors. Since the meaning of low peak levels is unclear and since most studies with multiple daily regimens confirm the lack of an association between trough levels and toxicity, we believe that monitoring of serum drug levels can be restricted to monitoring of trough levels in patients with a creatinine clearance below 50 ml/min or with a deteriorating renal function.

Adolescent↗
PubMed1996

Multicenter comparison of three commercial methods for quantification of human immunodeficiency virus type 1 RNA in plasma.

Three procedures for the quantification of human immunodeficiency virus type 1 (HIV-1) RNA from plasma were compared at three laboratories. The comparison involved the Quantiplex branched DNA assay (version 1.0) by Chiron Diagnostics, the NASBA-QT assay by Organon Teknika, and the Amplicor Monitor assay by Roche Molecular Systems. The laboratories performed each of the three assays with the same sets of reconstructed HIV-1-infected human plasma samples, cross-sectionally collected clinical plasma samples and longitudinally collected plasma samples from patients starting zidovudine therapy. Analysis of the reconstruction panel results for interlaboratory variation demonstrated that no laboratory differences in results were detected for any of the assays. A comparison of the reproducibilities of duplicate samples analyzed by batch and in separate assay runs demonstrated that the reproducibilities of the test results were similar within one assay and appeared to be independent of the HIV-1 concentration. The best reproducibility was obtained with the Quantiplex assay, but all three assays demonstrated equal reliability, which was independent of batched or unbatched analysis of replicate samples. Differences in the absolute concentrations calculated were observed for the assays, in particular in the analysis of reconstructed samples. In all assays, similar changes in plasma HIV-1 RNA concentrations were determined for longitudinally collected clinical samples.

Biomarkers↗
PubMed1996

A comparison of serum HIV-1 RNA levels as measured by two quantitative assays in zidovudine-treated, asymptomatic, HIV-infected individuals.

HIV-1 RNA levels as measured by two commercially available quantitative assays were compared before and during zidovudine treatment. HIV-1 RNA levels were measured in stored serum samples from 24 Dutch zidovudine-treated participants of a zidovudine efficacy study (European-Australian Collaborative Group Study 017) at weeks -3, 0, 4 and 8, using quantitative nucleic acid sequence-based amplification (NASBA; Organon Technika) and quantitative reverse transcriptase-polymerase chain reaction (Amplicor; Roche Molecular Systems). HIV-1 RNA copy numbers and changes from baseline as measured by each assay were compared. Individual responses to treatment were compared using definitions based on the within-subject variation of each assay. Before treatment, HIV-1 RNA levels as measured by NASBA were 0.49 logs higher than the levels measured by the Amplicor assay (95% confidence interval (CI) 0.32-0.66). During treatment, this difference decreased significantly to 0.27 logs (95% CI 0.01-0.53; difference 0.22 logs; 95% CI 0.05-0.37). The smaller difference between the results of the two assays during treatment was a consequence of a larger decline in RNA level as measured by NASBA compared with that measured by the Amplicor assay (mean change after 4 weeks 0.77 and 0.49 logs, respectively). At week 8, the mean HIV-1 RNA level was still significantly below baseline values as measured by NASBA, but not when measured by the Amplicor assay. Discrepancies in individual responses as measured by the two assays were also observed. In conclusion, marked differences exist between the NASBA and Amplicor quantitative assays, in both HIV-1 RNA copy numbers without treatment and changes in RNA level during treatment. These differences should be considered in interpreting analyses of clinical trials and relationships between HIV-1 RNA level and clinical outcome, as well as in the use of RNA level in the management of HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Soluble tumor necrosis factor receptors as surrogate markers for the assessment of zidovudine treatment in asymptomatic HIV-1 infection.

In untreated, asymptomatic human immunodeficiency virus type 1 (HIV-1) infection, elevated serum concentrations of soluble receptors for tumor necrosis factor (sTNFR) types I and II are associated with progression to AIDS. To assess the utility of sTNFRs as markers for the assessment of antiretroviral treatment, sTNFRs were sequentially determined in 47 asymptomatic HIV-1-infected men, who participated in a double-blind, randomized, placebo-controlled study. Progression to AIDS or severe AIDS-related complex occurred in six zidovudine (ZDV)- and six placebo-treated subjects. During ZDV treatment (n = 28) both types of sTNFRs declined compared with baseline and placebo, whereas they increased during placebo treatment (n = 19). A sustained decline of sTNFRs occurred only in subjects who experienced no disease progression. During the first 3 months of ZDV treatment, the hazard ratio for disease progression when sTNFR type II rose above the baseline value plus 5% was significantly increased (hazard ratio: approximately 25; 95% confidence interval: approximately 1.5-400; p < 0.03). Simultaneously determined CD4+ counts and serum neopterin levels showed a similar pattern in progressors and nonprogressors. Thus, in contrast to CD4+ counts and neopterin levels, sTNFR concentrations, especially those of the type II STNFR, appear to be valuable surrogate markers for monitoring the efficacy of ZDV treatment in asymptomatic HIV-1 infection.

AIDS-Related Complex↗