Fast track — ArticlesClinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study
Introduction
Highly active antiretroviral therapy (HAART) is currently the most important component of the treatment of HIV-1 infection. At present, HAART generally consists of one protease inhibitor combined with at least two nucleoside analogue reversetranscriptase inhibitors. The efficacy of HAART in suppression of plasma HIV-1 RNA to undetectable concentrations has been documented in clinical trials.1, 2, 3 The virological and immunological success rates reported from such trials may not, however, be generalisable to the whole population of HIV-1-infected patients.4 Furthermore, new opportunistic diseases or death are rarely used as endpoints in trials of HAART. It is widely accepted that plasma viral loads and CD4 cell counts reflect clinical efficacy, and virological and immunological responses are therefore used as surrogate endpoints. Viral load and CD4 counts are, however, imperfect surrogate markers that do not capture effects due to toxic effects or mediated through other causal pathways.5, 6
In the absence of trials assessing clinical endpoints, observational data are the only source of information relating new treatment regimens to the risk of serious clinical disease. Studies in the USA7 and Europe8, 9 have documented a substantial decrease in the risk of new opportunistic infections and of mortality after HAART was introduced. These studies have not, however, related virological responses to clinical progression.
We analysed the database of the national Swiss HIV Cohort Study to assess virological and immunological responses to HAART in routine care and to relate these findings to clinical disease progression.
Section snippets
Patients
The Swiss HIV Cohort Study is a prospective cohort study with continuing enrolment of HIV-1-infected patients aged 16 years or older.8, 10 Patients are followed up in one of seven outpatient clinics. Enrolment is independent of disease stage or degree of immunosuppression and information is collected according to standardised criteria at registration and follow-up visits every 6 months. Comparisons with the national AIDS registry have shown that the cohort includes 70% of patients with AIDS.10
Patients
Between September, 1995, and November, 1998, 3451 (65·1%) of 5298 patients followed up in the Swiss HIV Cohort study had started HAART. We excluded 252 (7·3%) patients who did not have at least one follow-up visit after HAART was started, and 525 (15·2%) with missing viral load or CD4 count at baseline. The analyses were based on 2674 (77·5%) patients (table 1). Included and excluded patients did not differ significantly for age, sex, transmission group, or clinical stage at baseline. History
Discussion
HAART led to suppression of viral replication in a substantial proportion of patients, but our results were less favourable than those from randomised trials.1, 3, 12 Gulick and colleagues3 showed that initial treatment with a triple-combination therapy, including a protease inhibitor, led to sustained suppression of viral load in pretreated patients. At 100 weeks, viral load continued to be undetectable in 78% of patients. Conversely, we found that 20–30% of pretreated patients never reached
References (28)
- et al.
Changing patterns of mortality across Europe in patients infected with HIV-1.
Lancet
(1998) - et al.
CD4-cell count in HIV-1-infected individuals remaining viraemic with highly active antiretroviral therapy (HAART).
Lancet
(1998) - et al.
Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance.
Lancet
(1998) Caution: should we be treating HIV infection early?
Lancet
(1998)- et al.
1998 revision to the British HIV Association guidelines for antiretroviral treatment of HIV seropositive individuals.
Lancet
(1998) - et al.
A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less.
N Engl J Med
(1997) - et al.
Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy.
N Engl J Med
(1997) - et al.
Simultaneous vs. sequential initiation of therapy with indinavir, zidovudine and lamivudine for HIV-1 infection.
JAMA
(1998) - et al.
Virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients.
AIDS
(1997) - et al.
Surrogate and auxiliary endpoints in clinical trials, with potential applications in cancer and AIDS research.
Stat Med
(1994)
Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection.
N Engl J Med
Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study.
BMJ
The Swiss HIV cohort study: rationale, organization and selected baseline characteristics.
Soz Präventivmed
Cited by (880)
Adherence to antiretroviral therapy among HIV positive men who inject drugs in Pakistan
2021, International Journal of Drug PolicyA stochastic delay model of HIV pathogenesis with reactivation of latent reservoirs
2020, Chaos, Solitons and FractalsA BAYESIAN DECISION FRAMEWORK FOR OPTIMIZING SEQUENTIAL COMBINATION ANTIRETROVIRAL THERAPY IN PEOPLE WITH HIV
2023, Annals of Applied StatisticsPhysical Activity as an Adjunct Treatment for People Living with HIV?
2023, American Journal of Lifestyle MedicineStaged HIV transmission and treatment in a dynamic model with long-term partnerships
2023, Journal of Mathematical BiologyViral Breakthrough Episodes among Persons with HIV in Care in Alberta, Canada: Clinical and Public Health Implications
2023, AIDS Patient Care and STDs
Members listed at end of paper