Apparent benefit from treatment interruption before multi-drug salvage therapy

This article is more than 22 years old.

Patients with heavy antiretroviral experience who begin a multi-drug salvage regimen comprising recycled agents, derive a stronger virological response if the regimen change is preceded by a drug-free period. That was the finding of the French ANRS 097 GIGHAART study presented by Professor Christine Katlama and colleagues from the Pitie-Salpetriere and Bichat Hospitals, Paris, today at the Fourteenth International AIDS Conference in Barcelona.

Seventy people with viral load above 50,000 copies, CD4 below 200, and prior experience of at least two protease inhibitors, two nucleoside analogues and one NNRTI were randomised to immediate or deferred “GIGHAART” therapy. The deferred group completed an eight week wash-out (off therapy) prior to the multi-drug regimen. The regimen consisted of three of four nucleoside analogues (either d4T, ddI, AZT, 3TC or abacavir), hydroxyurea (optional after April 2000), one NNRTI, and three protease inhibitors (ritonavir, amprenavir or lopinavir plus either indinavir, saquinavir or nelfinavir).

At baseline, median viral load was approximately 5.3 log, median CD4 was 27 cells, and median duration of prior therapy was approximately 6.5 years. Typical of such an advanced patients group, participants has been exposed to an average of eleven antiretrovirals (five nucleoside analogues, one NNRTI and four protease inhibitors).



Short for logarithm, a scale of measurement often used when describing viral load. A one log change is a ten-fold change, such as from 100 to 10. A two-log change is a one hundred-fold change, such as from 1,000 to 10.


A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

intent to treat analysis

All participants in a clinical trial are included in the final analysis, in the groups they were originally assigned to, whether or not they actually completed their course of treatment. This method provides a better estimate of the real-world effect of a treatment than an ‘on treatment’ analysis.

salvage therapy

Any treatment regimen used after a number of earlier regimens have failed. People with HIV who have experienced side-effects and/or developed resistance to many HIV drugs receive salvage therapy, sometimes consisting of a large number of medications.


The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

Twelve week efficacy data were presented at a European AIDS conference in Athens last year. These early results appeared to support the hypothesis that a period off treatment would allow the patients’ HIV population to revert from one that is largely drug resistant to one that is drug sensitive.

Responses after twenty-four weeks continue to show a benefit in the deferred treatment group. A significantly greater proportion of those undergoing a treatment interruption had at least a one log drop in viral load after 24 weeks (50% versus 24% by intent to treat analysis). The fall in viral load after twenty-four weeks was –1.08 log in the deferred group compared with –0.29 in the immediate group (p=0.013).

Treatment interruptions are associated with a fall in CD4 count, which is of obvious concern in patients who begin with such low CD4 counts. The GIGHAART study, however, found no difference in HIV-related adverse events between the two arms (three in the immediate group versus five in the deferred group).

Evaluation of plasma drug concentrations suggest the results were not explained by differences in drug exposure – the proportion of patients with adequate or low drug concentrations was similar in the two groups.

Whether this approach constitutes the best treatment strategy in this hard-to-treat population is unclear. In a separate presentation in Barcelona today, Dr Anton Pozniak of London’s Chelsea and Westminster Hospital, reported final 48 week results from Gilead’s 407 study which added tenofovir to the stable background antiretroviral therapy of patients with heavy drug experience and virological failure. After 48 weeks, the time-weighted changes in viral load was –0.57 log in the tenofovir group, and 41% had viral load below 400 copies.

GIGHAART was completed prior to the availability of tenofovir which, despite ongoing wrangles over its price (reported elsewhere today on, seems set to have a key role in salvage strategies. Speaking to Professor Katlama said: “We provided proof of principle on treatment interruptions. Imagine what you could do with tenofovir as well”.


Katlama C et al. Benefits of treatment interruption (TI) in patients with multiple therapy failures, CD4 cells 50,000 cp/ml (GIGHAART ANRS 097). Fourteenth International AIDS Conference, Barcelona, 7-12 July, abstract WePeB5887, 2002.

Pozniak AL et al. Tenofovir DF: A 48-week final analysis from a phase III randomized, double blind, placebo controlled study in antiretroviral treatment experienced patients (study 907). Fourteenth International AIDS Conference, Barcelona, 7-12 July, abstract WeOrB1266, 2002.