HIV-positive patients with a low CD4 cell count and no new treatment options who are taking antiretroviral therapy which is not controlling their viral load should remain on their therapy rather than interrupt treatment, French researchers report in the January 15th edition of Clinical Infectious Diseases.
Patients who interrupted treatment were much more likely to experience disease progression and develop new AIDS-defining illnesses that patients who stayed on their virologically-failing regimen, the French researchers found.
Potent anti-HIV therapy significantly reduces the risk of HIV disease progression by suppressing HIV replication and allowing the recovery of the immune system. A detectable viral load during antiretroviral therapy can lead to the development of drug-resistant strains of HIV.
Two treatment strategies are often advocated for patients who have extensive experience of anti-HIV treatment, limited new drug options and ongoing replication of drug-resistant HIV: either maintain the existing treatment, often with additional “re-cycled” drugs; or, temporarily interrupt HIV treatment, hopefully allowing drug-sensitive HIV to once again emerge.
There are conflicting results from studies looking at both treatment strategies.
But no study has looked at HIV disease progression in extensively-treated patients who remain on a virologically failing treatment compared to such patients who interrupt treatment. It is therefore unknown if treatment interruption because of virologically failing treatment in patients with a low CD4 cell count – below 200 cells/mm3 - is a safe strategy.
Investigators therefore analysed data from the French HIV hospital database. They identified patients enrolled between 2000 – 2005 who had a CD4 cell count below 200 cells/mm3 and who had taken one or more antiretroviral regimens for six or months.
These patients were divided into three groups: patients who interrupted treatment; those who remained on treatment despite having a viral load above 500 copies/ml; and those who took anti-HIV treatment and maintained an undetectable viral load.
Information was gathered on the development of AIDS-defining illnesses in each of the three groups of patients.
A total of 12,765 patients were included in the investigators’ analysis, and 72% of these patients were men.
Anti-HIV therapy was interrupted by 2,399 patients and 39% of these had a viral load above 30,000 copies/ml. The number of patients who stayed on anti-HIV therapy with a detectable viral load was 8,783 and 46% of these patients had a viral load above 30,000 copies/ml. Overall, 4,351 patients who took anti-HIV treatment and had an undetectable viral load.
A new AIDS-defining illness was recorded in 348 patients in the treatment interruption arm, with an incidence of 18.5 cases per 100 patient years of follow-up. Of these, 99 (29%) occurred in the first month after treatment was stopped.
New AIDS events were recorded in 1483 patients who stayed on a virologically failing therapy, providing an incidence of 14.5 caser per 100 patient years of follow-up. Of these new AIDS-defining illnesses, 189 (13%) were diagnosed in the first month of follow-up.
A total of 310 patients who took anti-HIV therapy and had an undetectable viral load developed an AIDS-defining illness, an incidence of 4.5 cases per 100 patient years. Of these, 59 (19%) occurred during the first month of follow-up.
For each group of patients the incidence of new AIDS-defining events was higher for patients with a CD4 count below 50 cells/mm3 compared to those with a CD4 cell count between 150 – 200 cells/mm3. New AIDS-defining illnesses also occurred more frequently in patients with a baseline viral load above 30,000 copies/ml compared to patients with a baseline viral load below this value.
When the investigators looked at the incidence of individual AIDS-defining events, they found that each occurred with significantly greater frequency in patients who interrupted therapy than amongst patients who either remained on a virologically failing regimen, or amongst patients who took treatment and had an undetectable viral load.
Overall, amongst patients with a CD4 cell count below 50 cells/mm3, compared to individuals who interrupted therapy, those who remained on treatment with a detectable viral load were 22% less likely to develop a new AIDS-defining illness, with patients with an undetectable viral load some 62% less likely to progress to a new AIDS event.
For patients with a CD4 cell count between 50 – 200 cells/mm3, compared to patients who stopped anti-HIV treatment, individuals who continued therapy with a detectable viral load were 34% less likely to progress to a new AIDS event, with treated patients with an undetectable viral load being some 73% less likely.
“Patients with detectable viral load who continued antiretroviral therapy had lower incidence and risks of AIDS-defining events of all types than did patients who stopped their treatment, both in the overall population and after CD4 cell count stratification”, comment the investigators.
They add, “our study confirms that interruption of antiretroviral therapy has a negative prognostic impact, even in the most advance patients.”
“Maintenance of a failing drug regimen to which the patient’s HIV quasispecies is resistant may still interfere with viral replication and thereby slow the immunological and clinical deterioration”, suggest the investigators.
The investigators conclude, “our results suggest that, when profoundly immunodeficient HIV-infected patients have no further treatment options permitting effective viral control, maintaining a failing regimen is preferable to interrupting it.”
Kousiginian I et al. Maintaining antiretroviral therapy reduces the risk of AIDS-defining events in patients with uncontrolled viral replication and profound immunodeficiency. Clin Infect Dis 46: 296 – 304, 2007.