Risk of viral rebound decreases with longer treatment, even with previous failures

The risk of treatment failure is, at least initially, greater for people with a larger number of previous treatment failures. However, a large cohort study has shown that after four years on therapy, failure rates are not only much lower, but do not vary according to previous treatment failures. These results, published in the journal AIDS, derive from an analysis of over 10,000 virologically suppressed participants in the United Kingdom Collaborative HIV Cohort study.

Continued viral suppression – the continued reduction of HIV plasma viral load to levels

In this study, a team of UK researchers looked for the effects of the number of previously failed regimens and the duration of viral suppression on the rates viral rebound. Data were taken from the very large United Kingdom Collaborative HIV Cohort (CHIC) Study, and included patients being seen at seven of the largest HIV clinics in the UK. Of the 21,256 participants in this observational cohort, 12,648 received antiretroviral therapy (defined as a combination of three or more antiretrovirals) at some point during follow-up. Of these, 10,237 (80.9%) achieved viral suppression (a viral load

Analyses were based on occurrence rates per person-year of follow-up; the 10,237 participants contributed a total of 26,494 person years. Participant characteristics were as follows (numbers reflect the percentage of total person years contributed):

• 84% (22,205 person years) contributed by male participants
• 68% white, 17% black-African, 16% other
• CD4 count (cells/mm³) at time of first viral suppression: less than 200 - 24%; 200 to 350 - 31%; greater than 350 - 40%; unknown - 5%
• Number of previous failing regimens: 0 - 53%; 1 - 22%; 2 - 14.3%; 3 - 7%; 4 or more - 4%.
• Duration of viral load

Viral rebound was defined as two consecutive viral load measurements ≥ 400 copies/ml, or a single value of ≥ 400 copies/ml if two or more new drugs were started as a result. Multiple rebound “events” were counted into the analysis; i.e., if a study participant successfully regained viral suppression after a rebound but then rebounded again, each of these events was counted separately. Any treatment taken before January 1996 counted as one failed regimen, regardless of viral load.

Rebound happened at least once in 1,853 (18%) of the participants: there were a total of 2,460 rebound events, for an overall rate of 9.3 per 100 person years.

Factors associated with greater risk of rebound were:

• beginning therapy between 1996 and 1998 (relative risk (RR) 2.17; 95% CI 1.82 – 1.73)
• black ethnicity (RR 1.48, 95% CI, 1.26 – 1.73)
• greater numbers of previously failed treatments (38% increase in risk per failed regimen: RR 1.38, 95% CI 1.34 – 1.42)
• shorter duration of viral suppression (32% reduction in risk per year of suppression: RR 0.68, 95% CI 0.68 – 0.70)

Within the first year of suppression, the number of previously failed regimens made a highly significant difference. However, with longer duration of successful treatment, not only did the rates of viral rebound drop, but so did the difference due to the number of previous failed regimens. After four years or more, rebound rates were similar regardless of the number of previous failed regimens (see table):

Rates of viral rebound, per 100 person-years (95% confidence intervals [CI]):

“In conclusion,” the report states, “in those patients with suppression, previous failure is associated with a higher rate of viral rebound, but the likelihood of rebound declines with the duration of suppression… Achievement of viral suppression in a patient with previous multiple failures is followed by a period of high rebound-risk that requires careful ongoing management and support… [after four years of suppressive therapy] rebound rates even after multiple previous therapy failure fall to levels approaching those of patients on first line therapy.”