Treatment interruption prior to five-drug regime shows no benefit at 48 weeks
1 November 2003. Related: Treatment strategies.
Simon Collins, HIV i-Base
When the French GIGA-HAART study reported significant short-term benefits from a two-month treatment interruption (followed by an eight- or nine-drug GigaHAART regimen with PI drug levels optimised by therapeutic drug monitoring) compared to continuous treatment, the study was stopped early. [1] Whether this strategy resulted in longer-term benefit was therefore not established.
In the October 2003 issue of HTB we reported on a recent NIAID study that reported an increased risk of disease progression in patients who took a four-month interruption compared to patients using continuous therapy – and which was widely reported as discouraging any break in treatment.
The 1 October issue of the Journal of Infectious Diseases reports results from a Spanish group that provides additional data on this difficult option. [3]
In this study, Ruiz and colleagues randomised 46 heavily treatment experienced patients to either switch straight to five-drug salvage therapy (Kaletra, Fortovase 1000mg BD, abacavir, ddI, 3TC) (n=24) or to take a 12 week treatment interruption prior to the new five-drug treatment (n=22).
No differences between the groups were seen after six months (when reported at the 9th Retrovirus conference, Abstract 421) and similar responses are reported after one year in the HID paper. At week 48, 45% of patients in the interruption group and 46% of patients in the continuous treatment group had viral loads <50 copies/mL (p=0.619). No differences in CD4 cell counts were seen between groups at week 48 (p=0.734).
A complete reversion to wild-type genotype was detected in 35% of patients in the interruption group, and median genotypic mutations dropped from 10.8±4.8 at baseline to 3.8±4.2 after the three month interruption, but this did not affect the long-term virological response.
However, although this was a highly resistant group, they were also relatively healthy with baseline median CD4 and viral load counts in the interruption group of 383 cells/mm3 (84-783) and 4.3 copies/mL (range 3.2-5.3).
The only overall baseline factor associated with ensuing virus suppression was a lower number of nucleoside reverse-transcriptase inhibitor–resistant mutations (relative risk, 0.66; 95% CI, 0.47–0.93; p=0.021).
In this study an interruption prior to treatment produced no additional benefit to subsequent virological or immunological outcomes of the salvage regimen.
References:
- Katlama C, Dominguez S, Duvivier C et al. Benefits of treatment interruption (TI) in patients with multiple therapy failures, CD4 cells <200 /mm3 and HIV RNA >50 000 cp/ml (GIGHAART ANRS 097). XIV International AIDS Conference, Barcelona 7-12 July. Abstract WePeB5887. See HTB Vol3 No7.
- Lawrence J et al. Structured treatment interruption in patients with multidrug-resistant human immunodeficiency virus. The New England Journal of Medicine 349(9):837-46 (2003). See HTB Vol4 No8.
- Ruiz L, Ribera E, Bonjoch A et al. Role of structured treatment interruption before a five-drug salvage antiretroviral regimen: the Retrogene Study. The Journal of Infectious Diseases 2003;188:977-985