Adverse events and treatment interruption in tuberculosis patients with and without HIV co-infection.

BACKGROUND: Serious treatment associated adverse events are thought to occur more frequently in individuals with tuberculosis (TB) who are co-infected with HIV. A study was undertaken to assess the frequency of serious (grade III/IV) adverse events and interruption of anti-TB treatment in the era of effective antiretroviral therapy. METHODS: The incidence of serious adverse events was retrospectively compared in 312 individuals treated for TB, 156 of whom were co-infected with HIV. RESULTS: 111 HIV infected individuals (71%) received highly active antiretroviral therapy at the same time as anti-TB treatment. Serious adverse events were recorded in 40% HIV infected and 26% HIV uninfected individuals (p = 0.008). Peripheral neuropathy and persistent vomiting were more common in co-infected patients (p<0.001; p = 0.006), although all cause interruption of anti-TB treatment occurred with similar frequency in the two groups (13% in HIV infected patients and 15% in HIV uninfected patients; p = 0.74). In 85% of HIV infected patients and 87% of HIV uninfected individuals this was due to hepatotoxicity, which typically presented within 2 months of starting treatment. The median delay in restarting treatment was 4 weeks, so most individuals required full TB re-treatment. CONCLUSION: Despite a greater rate of serious (grade III/IV) adverse events among HIV infected individuals, discontinuation of anti-TB treatment occurred with a similar frequency in HIV infected and HIV uninfected individuals.

Virological response to highly active antiretroviral therapy is unaffected by antituberculosis therapy.

We compared 156 human immunodeficiency virus (HIV)-infected patients who had tuberculosis with control populations of similar size. Of 111 patients with HIV infection and tuberculosis who received highly active antiretroviral therapy (HAART) and therapy for tuberculosis concurrently, 92 (83%) achieved or maintained virus loads of <50 copies/mL, and 99 (89%) achieved or maintained a >or=2 log10 reduction in virus load after 6 months. Virological response and changes in CD4 cell count were equivalent to those in 111 matched HIV-infected subjects without tuberculosis starting HAART. Tuberculosis recurrence rates were similar to those found in an HIV-uninfected population of 156 subjects (3% and 1%, respectively). Treatment for HIV and tuberculosis does not compromise outcomes for either disease.

Participation in clinical studies among patients infected with HIV-1 in a single treatment centre over 12 years.

OBJECTIVE: To examine a complete population of clinic attenders in order to compare the demographics of patients who participated in a clinical study with those who had not. These were subdivided into trials of antivirals, trials for drugs used in opportunistic infections or symptomatic HIV and epidemiological studies. The setting was an established London teaching hospital. All patients diagnosed HIV-positive and attending between July 1983 and 1 January 1999 with one measured CD4 count and at least one follow-up visit were included. METHODS: The demographics of those participating in a clinical study were compared to those not enrolling using chi2 tests and Wilcoxon tests. Cox models were used to determine factors related to participation in clinical studies. RESULTS: Data from 2703 patients representing 5342.7 person-years' follow-up were assessed. Median time of follow-up was 23.6 months. Six hundred and eighty-seven (33%) patients had ever participated in a clinical study. After adjustment for demographic factors in multivariate analysis using Cox models, homosexuals were more likely to participate compared with heterosexuals or injecting drug users (IDU) (P = 0.0035 and P = 0.0001, respectively). Women were more likely to enter a study (P = 0.02) and there was no difference between Caucasians and black Africans (P = 0.35). Between the three types of studies few differences were seen. CONCLUSION: High rates of participation in clinical trials and epidemiological studies were seen in this cohort. In keeping with other studies, homosexual men were well represented but IDU were under-represented. However, women and black African patients showed good uptake of all clinical studies. Hence in this population there is some success in targeting representative groups to participate in clinical studies, but more effort needs to be made with IDU.

Changing treatment patterns among patients with HIV: Royal Free Hospital 1987-97.

OBJECTIVE: Following the publication of results of large-scale clinical trials, antiretroviral treatment for HIV has changed dramatically. The aim of this study was to describe changes in antiretroviral treatment and the way treatments were combined among 1806 patients with HIV seen at a single centre at the Royal Free Hospital, London, UK. DESIGN AND METHOD: Each calendar year was divided into quarters, and the number of patients receiving treatment and participating in clinical trials was determined. RESULTS: The proportion of patients on no therapy decreased from over 90% at the beginning of 1988 to under 15% at the end of 1997. Monotherapy was the only form of treatment available before 1992 but its use dropped to 2% by the end of 1997. The standard of care at the end of 1997 was triple combination therapy, used in over 40% of patients. There were dramatic changes in the use of individual agents; use of zidovudine decreased from 50% during 1989 to 25% during 1997, while use of lamivudine and stavudine saw an exponential rise in 1997. The protease inhibitors were used in equal proportions in this clinic population; the use of dual protease therapy began in 1997 and was rising rapidly by the end of the year. CONCLUSIONS: There have been major changes in the use of antiretroviral therapy at this centre, particularly during 1996 and 1997. The long-term cost implications and side-effects of intensive treatment regimens remain to be addressed.

Health economics. Perfect combination.

The assumption by some HAs that a shift from mono to combination drug therapies for HIV results in a proportional increase in drug expenditure, regardless of health gains, is misguided. Methods of calculating anti-HIV drug expenditure have failed to keep up with changing treatment regimes. There is an urgent need to change the way data on antiretroviral use is collected and presented to establish the true cost-effectiveness of new drug regimes.