ABSTRACT:
Individuals taking HAART regimens for the first time usually experience suppression of viral load to levels below 500 copies/ml or lower. Subsequent viral rebound back above this level, however, is not uncommon. Development/selection of drug-resistant virus has been suspected as a major cause of such rebound, but other factors, such as incomplete adherence are known to play a role. Our aim was to evaluate the prospects for long-term maintenance of viral suppression when HAART is initiated in naïve patients. We followed 406 drug-naïve patients starting a three- or four-drug HAART regimen (including at least two NRTIs and wither a PI ofr an NNRTI) in the Frankfurt HIV Clinic Cohort. The median initial viral load and CD4 count were 5.4 log copies/mL and 259 cells/mm3, respectively. Viral load was measured on average every 4 weeks during follow-up. Ninety-one percent reached viral load <500 copies/mL by 24 weeks and there was a median 4.8.log decrease in viral load by week 48 (n=235); accounting for lower limit censoring of viral load). Among people in whom viral load was reduced to <500 copies/mL, viral rebound (two consecutive values >500 copies/mL) occurred in 69 during 344 years of follow-up (rate=2.0 per 10 years). There was a 21% probability of viral rebound by 1 year after initial suppression <500 copies/mL, 28% by 2 years. Cox regression analysis, stratifying by calendar year, indicated that there was a significant decrease in the rate of viral rebound with increasing length of viral suppression <500 copies/mL (relative hazard 0.38 per 1 year more suppression; P=0.005), with a rate of only 0.8 rebounds per 10 years (8 rebounds in 99 person-years; i.e. average of 1 rebound per 12.4 years) in people who had experienced viral load <500 copies/mL for over 1 year. This low and decreasing rate of viral rebound in patients with at least 1 year viral suppression implies that, if prolonged complete drug adherence were possible, long-term viral suppression for 10 years and more seems within the capacity of presently available regimens. Viral rebound consequent on resistance to drug therapy is thus certainly not inevitable over this time span.
