Search

In a randomized, parallel arm, open-label study, the effect of switching from ritonavir to either nelfinavir or nelfinavir plus saquinavir as part of a triple antiretroviral regimen was investigated in 16 patients with undetectable HIV-1 loads. Patients continued to use the same nucleoside reverse transcriptase inhibitors as before the switch of protease inhibitor. The period of follow-up was 48 weeks. In all patients HIV-1 load remained undetectable, whereas CD4 cell counts remained stable. Furthermore, lipid markers improved after the switch.

This study investigated the attitude towards antiretroviral therapy (ART) for HIV infection over time, in a sample of Dutch general practitioners (GPs). Twenty-one GPs, of which 16 were practising in Amsterdam, completed multiple questionnaires on HIV-related topics between April 1995 and March 1997. In 1995, only 10% had a positive attitude towards treatment of asymptomatic persons with a CD4+ > 300 x 10(6)/l; at the end of the study 43% had. In 1995, 57% had a positive attitude towards treatment of asymptomatic persons with a CD4+ < or = 300 x 10(6)/l, and 52% towards treatment of symptomatic patients with a CD4+ < or = 400 x 10(6)/l; heterosexual GPs more often had a positive attitude as compared to homosexual GPs (p = 0.005 and p = 0.01, respectively). At the end of the study the proportions of GPs with a positive attitude had increased from 57 to 81% and 52 to 95%, respectively. The risk of adverse effects, strict dose regimens and medicalization were regarded as the main disadvantages of the current treatment strategy. The conclusion is that the attitude towards ART has become more positive since 1995. At the beginning of 1997, however, there still existed reservations about treatment of asymptomatic persons with CD4+ cell counts > 300 x 10(6)/l.

Objective: We aimed to compare, in a sample of Amsterdam general practices, the monitoring and treatment status of HIV-infected patients according to the 1991 Dutch consensus guidelines for antiretroviral treatment of HIV-infection, which advise that therapy be started at a peripheral blood CD4+ cell count of < or = 300 x 10(6)/l in asymptomatic patients, or < or = 400 x 10(6)/l in symptomatic patients., Method: In 1994, data were collected from the records of all 511 HIV-infected patients registered in 14 Amsterdam general practices (20 doctors). The main outcome measures were the antiretroviral treatment status of all patients who were eligible for treatment, and the disease stage and CD4+ cell counts at the onset of therapy for patients who started treatment after publication of the 1991 guidelines., Results: For 472 patients, data were available on CD4+ cell measurement status and disease stage. For 15.9% of patients, CD4+ cells had never been measured; most of them were asymptomatic. In 84.1 % of patients, CD4+ cells had been measured. Of the 8.9% of patients whose results were not known to GPs, 93% were treated by a specialist and 76% were symptomatic. Of the remaining 355 (75.2%) patients whose CD4+ count and disease status were known, 201 (56.7%) met the guideline criteria for treatment. Of these, 53.7% received treatment, 27.4% were never treated and 18.9% had discontinued treatment. Of the 67 patients who started treatment after publication of the guidelines, 36.2% of asymptomatic patients and 92.8% of symptomatic patients started later than the guidelines advised., Conclusion: In the population studied, we found a discrepancy between the 1991 treatment guidelines and the actual situation. In a substantial proportion of eligible patients, antiretroviral treatment was either not administered at all or was administered at a (very) late disease stage. This can only be attributed to physicians' and/or patients' attitudes towards antiretroviral treatment. Other studies confirm that a number of psychological factors may influence treatment decisions. The new combination treatment of HIV-infection requires an early start and compliance with the guidelines. The degree to which doctors and patients are willing and able to comply with the guidelines is an important factor to be taken into account, both in research and in the development of guidelines.

A77003, an inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, was administered to asymptomatic HIV-1-infected patients in a phase I trial. The drug was given by continuous intravenous infusion at dosages of 0.035, 0.07, 0.14, and 0.28 mg/kg of body weight per h. The drug was given first for 24 h and then for up to an additional 4 weeks in a second infusion period following at least a 6-day washout. Apart from reversible increases in hepatic transaminase levels in some patients, no systemic toxicities occurred during extended infusion of the drug. Dose-related local vein irritation, despite dilution of the infusate, however, caused severe infusion site phlebitis precluding dosage escalation beyond 0.28 mg/kg/h. Pharmacokinetic analysis demonstrated dose linear increases in mean steady-state concentrations. However, clearance of the drug from plasma was unexpectedly high, averaging 62 liters/h across all groups. The concentrations of A77003 in plasma achieved the in vitro 50% inhibitory concentration (0.16 microgram/ml) only in the 0.28-mg/kg/h dosage group, but it did not attain the 90% inhibitory concentration (0.48 micrograms/ml). No statistically significant effect on CD4 cell numbers occurred in any of the groups, and there was no evidence of antiviral activity, as determined by HIV-1 p24 antigen level, quantitative plasma and cell culture, and quantitation of viral RNA in plasma. In conclusion, A77003, as formulated in the present study, causes severe phlebitis, which prevents administration of the infusates necessary to achieve high concentrations of the drug in plasma. In conclusion, A77003, as formulated in the present study, causes severe phlebitis, which prevents administration of the infusates necessary to achieve high concentrations of the drug in plasma. The lack of antiviral activity observed in the study may be a consequence of the low concentrations in plasma in all groups.