After 4 Years
of Viral Suppression with HAART, HIV Rebound Rates in Patients with Multiple Prior
Treatment Failures Resemble Those in Individuals with No Prior Failure
Researchers with the United Kingdom
Collaborative HIV Cohort (CHIC) Study investigated whether the rate of viral rebound
decreases with increasing duration of viral suppression with HAART and, if so,
whether rebound rates in patients previously failing antiretroviral regimens ultimately
decline to levels as low as those seen in patients who have never experienced
virological failure.
In the July 11, 2007 edition of AIDS, Andrew
Benzie and colleagues report on the results of a study suggesting that a long
period of viral suppression correlates with lower HIV rebound rates in people
who have previously experienced treatment failure.
All patients from the
UK CHIC Study (n = 21,256) who achieved a viral load of </= 50 copies/mL while
receiving HAART were followed until viral rebound (2 consecutive viral loads >
400 copies/mL). Patients could re-enter the analysis if they experienced a subsequent
viral load </= 50 copies/ml. Rebound rates were calculated according to the
number of regimens previously failed and duration of viral suppression.
Results
• Of 12 648 patients
on HAART 10,237 (80.9%) achieved a viral load </= 50 copies/mL.
•
During 26,494 person-years (PY) of follow-up, 1853 patients (18.1%) experienced
at least 1 viral rebound event, with 2460 events in total (rebound rate 9.3 [range
8.9-9.7]/100 PY).
•
Within the first year of viral suppression, the rate of viral rebound was 8.3
(7.5-9.1)/100 PY in patients who had not previously failed treatment, increasing
to 32.7 (27.6-37.8)/100 PY in patients who had failed more than 4 regimens.
• Irrespective
of previous treatment failure, rebound rates in those who remained suppressed
for > 4 years were similar to those in patients who had at no time experienced
treatment failure.
The
authors concluded that after approximately 4 years of viral suppression, rebound
rates in individuals with multiple prior treatment failures approach those of
individuals with no prior treatment failure.
Discussion
Results
of the current study indicate that a lower baseline CD4 cell count was a significant
predictor of viral rebound, as concluded based on a prior study (1). A possible
explanation for this is that some drugs are not maintained at optimal levels in
patients with low CD4 cell counts because of poorer drug absorption, drug-drug
interactions, adherence, or other factors.
Baseline viral load at the start
of antiretroviral therapy was not associated with an increased risk of rebound,
according to the study authors. This result differs from the findings of a prior
study in which lower HIV-1 RNA levels at the time of starting treatment independently
predicted a higher chance of therapeutic success in terms of achieving and maintaining
an undetectable viral load (2).
The authors also found an association between
black ethnicity and an increased risk of viral rebound. They surmise that this
effect may be due in large measure to socioeconomic factors. Interestingly, the
investigators concluded that older age was a significant predictor of a better
response in this study. Prior studies have also demonstrated that younger age
is associated with poorer responses to therapy (3).
The study authors
emphasized the importance of avoiding treatment failure. This can be done by taking
anti-HIV medications on time and as recommended. Maintaining a high level of treatment
adherence keeps drug levels in the body steady and at the most effective amounts.
This limits the ability of HIV to replicate and prevents the development of drug
resistance, both of which contribute to viral rebound.
In closing, the
authors wrote, "Both clinicians and patients can be encouraged that regardless
of previous treatment failure, rebound rates even after multiple previous therapy
failure fall to levels approaching those of patients on first line therapy after
4 years of suppressive therapy. This has important implications for providing
treatment support and advice during those 4 years of follow up."
St
Mary's Hospital, London, UK Royal Free & University College Medical School,
London, UK Royal Free NHS Trust, London, UK dGuys, Kings and St. Thomas School
of Medicine, London, UK Chelsea and Westminster Hospital, London, UK, Brighton
and Sussex University Hospital Trust, Brighton, UK Barts and the London NHS Trust,
London, UK, Medical Research Council Clinical Trials Unit, London, UK, Health
Protection Agency-Centre for Infections, UK.
07/06/07
Source
A A Benzie, L K Bansi, C A Sabin, and others (on behalf of the United
Kingdom Collaborative HIV Cohort (CHIC) Study). Increased duration of viral suppression
is associated with lower viral rebound rates in patients with previous treatment
failure. AIDS 21(11): 1423-1430. July 11, 2007.
References
1.
V Miller, S Staszewski, C A Sabin, and others. CD4 lymphocyte Count as a Predictor
of the Duration of Highly Active Antiretroviral Therapy-induced Suppression of
Human Immunodeficiency Virus Load. Journal of Infectious Diseases 180:
530-533. 1999.
2. R Paredes, A Mocroft, O Kirk, and others. Predictors
of Virologic Success and Ensuing Failure in HIV-positive Patients Starting Highly
Active Antiretroviral Therapy in Europe. Archives of Internal Medicine
160: 1123-1132. 2000.
3.
J J Parienti, V Massari, D Deschamps, and others. Predictors of Virologic Failure
and Resistance in HIV-infected Patients Treated with Nevirapine or Efavirenz-based
Antiretroviral Therapy. Clinical Infectious Diseases 38:1311-1316. 2004.
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