The Long-Term Impact of Early Virologic Control

Nicolai Lohse and colleagues from Odense University Hospital in Denmark have been analyzing patient records from Denmark's HIV Cohort, a nation-wide study of nearly every person on antiretroviral (ARV) therapy in that country. They have previously reported that virologic failure among patients who first started triple combination ARV therapy before 1999 was far more common than in those who began therapy after 1999. This finding is probably due to the advanced stage of disease in the earlier group, and due to preexisting NRTI resistance caused by prior use of one- and two-drug regimens.

A new report by Lohse et al finds that maintaining virologic control during the one-year period after the first six months of therapy (months 6 to 18) is predictive of improved CD4 cell count, survival, and the likelihood of successful viral suppression after follow up out to 7.5 years. Six months on therapy was chosen as a starting point for this study because by that point most patients will have gotten over the initial side effects of treatment and will have settled into a pattern of good adherence and sustained viral suppression.

The study cohort of 2046 patients was divided into three groups according to the success of viral suppression during the yearlong period from 6 to 18 months after starting triple drug therapy. Group 1 (1,173 pts) had HIV RNA <400 copies/mL throughout the entire year. Group 2 (546 pts) were below 400 copies/mL only part of the time; and Group 3 (327 pts) had detectable HIV RNA at every measurement during the year. At 72 months of follow-up, 92.7% of patients in Group 1 were still alive compared to 76.1% of patients in Group 3. Survival in Group 2, those with partial suppression, was 85.6%. Viral load was suppressed in 96% of those in Group 1, 83% in Group 2, and in only 57% of those in Group 3. CD4 counts improved in all groups, but were significantly higher in Groups 1 and 2 than in Group 3. A subgroup of unsuppressed patients who took a treatment interruption during the first 18 months of therapy had a higher death rate than patients in Group 3. The most common reasons for interruption were adherence difficulties (30%), patient choice (25%), and drug intolerance (27%).

The initial characteristics of members of the three groups may have bearing on their success at long-term viral control. While baseline age, sex, race, and viral load were comparable among the groups, Group 3 patients had lower CD4 counts, were more likely to have injected drugs and have hepatitis C, and had much greater prior exposure to ARVs. In reference to the earlier research by Lohse et al on the timeframe for starting treatment, 47% of Group 1 started therapy after 1998 compared to only 16% of those in Group 3 and 27% in Group 2. This suggests that underlying factors such as prior resistance, hepatitis C coinfection, social and economic status, and generally poorer immunological and clinical condition may have contributed to inferior long-term outcomes for many patients in this cohort. These factors may also affect individuals' ability to practice the perfect adherence required to maintain viral suppression.

Lohse N, Kronberg G, Gerstof J, et al. Virologic control during the first 6-18 months of initiating highly active antiretroviral therapy as a predictor for outcome in HIV-infected patients: A Danish, population-based, 6-year follow-up study. Clinical Infectious Diseases. 2006;42:136-44.