Behandeling van HIV-1 in Nederland: virologische en immunologische respons op antiretrovirale therapie

To evaluate the effect of treatment of HIV-1 infection with combination therapy consisting of since 1996 in the Netherlands available protease and reverse transcriptase inhibitors.

Design

Prospective cohort study.

Methods

In an observational clinical cohort of HIV-1-infected individuals, the short-term successful treatment end point of antiviral therapy including at least one antiretroviral drug licensed in the Netherlands since July 1, 1996 (protease inhibitors and reverse transcriptase inhibitors), was HIV-1 RNA plasma levels ≤ 500 copies/ml (virological success). Cox proportional hazard models were used to identify prognostic markers for therapy success. The study included 2,148 infected individuals with a median follow-up of 135 weeks of treatment; 1,049 had been pre-treated with antiretroviral drugs before starting their new regimen and 1,099 were treatment naive.

Results

Plasma HIV-1 RNA levels ≤ 500 copies/ml at 24 weeks of treatment were seen in 61 of all patients. The chance of therapy success for naive patients was twice that for pre-treated patients (relative risk: 1.8; p ≤ 0.001). Following the first 24 weeks, the chance of virological success was higher in the naive group (78 versus 63; p ≤ 0.001), and the number of naive patients failing therapy after initial success was smaller compared to pre-treated patients (22 versus 45; p ≤ 0.001). In the naive group, the CD4⁺ T-cell number increased from 239 to 440 (× 10⁶ cells/l) in case of success, and decreased from 150 to 320 in case of treatment failure. HIV-1 related morbidity declined from 0.26 to 0.05 and mortality dropped from 0.07 to 0.03 per person-year of follow-up. Regimens were changed at least once in 76 of patients. Toxicity and therapy failure were the main reasons for regimen changes in naive and pre-treated patients, respectively.

Conclusion

A combination of antiretroviral drugs, including at least one of the drugs licensed since 1996, led to a drop in HIV-1 plasma concentrations. Morbidity and mortality also decreased. The chance of a better immunological and virological response to the new drug regimens was greatest in therapy-naive patients.