Achieving a sustained suppression of HIV viral load in the first 18 months of treatment with HAART is a predictor of longer-term prognosis according to a study conducted by Johns Hopkins University and published in the July 1st edition of the Journal of Acquired Immune Deficiency Syndromes.
The study included 444 patients who started a HAART regimen containing a protease inhibitor or NNRTI between March 1996 and December 1998. The patients were followed for four years to determine the impact of response to HAART in the first 18 months of treatment on longer-term prognosis.
Three potential responses to treatment were assessed by the investigators: a sustained suppression of HIV viral load to below 500 copies/mL (the suppression group); or initial suppression of HIV replication to below 500 copies/mL followed by subsequent rebound to more than 1000 copies (rebound patients); or, no suppression to below 500 copies/mL (treatment failure). Investigators assessed long-term patterns in antiretroviral use, changes in CD4 and viral load, survival, and the risk of developing abnormal blood lipids for these groups.
Response to therapy
Thirty-six percent of patients achieved sustained viral suppression, 26% rebounded and 38% did not achieve viral suppression. The patients experiencing sustained viral suppression were more likely to be gay men, and have a lower baseline viral load (50,000 copies/mL versus 80,000 copies for the rebound and failure patients), and a higher CD4 cell count (223 cells/mm3 versus 130 cells/mm3 for rebound patients and 168 cells/mm3 for treatment failure patients).
HAART use
Unsurprisingly, patients with sustained viral suppression used more HAART, taking anti-HIV therapies 82% of the time compared to 60% for the rebound group (p
Resistance tests were performed on 14% of the suppression patients, 30% of the rebound group, and only 10% of the failure patients.
Changes in HIV viral load and CD4 cell count
Patients achieving suppression had the most HIV viral load tests and CD4 cell counts performed during follow-up (17 and 13 respectively versus, 16 and eleven in the rebound group and five and four in the failure group, p
In the four years of follow-up, 86% of the suppression group had at least one viral load test below 500 copies/mL compared to 57% of the rebound group and 35% of the failure group (p
Survival
The investigators calculated that after five years of HAART, 89% of the suppression group, 76% of the rebound group (p=0.4), and 56% of the failure group (p
Compared to the survival group, the relative risk ratio for death was 1.8 (95% CI: 0.9 – 3.5) for the rebound patients and 3.5 (95% CI: 2.0 – 6.4).
Metabolic abnormalities
After four years of follow-up, 35% of the suppression group had diabetes or increased blood lipids compared to 24% of the rebound group and 8% of the failure to suppress patients. Virological response was strongly associated with a risk of these metabolic abnormalities.
Time on HAART was a significant predictor for the development of diabetes or increased blood lipids, with a hazard ratio of 1.2 per each additional 10% of time on HAART (95% CI 1.1 – 1.3, p
Conclusions
”Our findings highlight the prognostic implications of response to HAART in the first 18 months. Patients achieving durable viral suppression had a very low risk of death, whereas 5-year mortality was 44% in patients who did not achieve viral suppression”, note the investigators.
They also note that patients who did not achieve a virological response to therapy used HAART less, and that aggressive efforts should be made to engage such patients with HIV care, and directly observed therapy should be considered, particularly for patients with factors which predict poor adherence such as drug use or mental illness.
Further information on this website
HAART has led to a sustained reduction in AIDS and death in EuroSIDA cohort - news story
Prognosis - factsheet
Lucas GM et al. Survival in an urban HIV-1 clinic in the era of highly active antiretroviral therapy: a 5-year cohort study. JAIDS 33: 321 – 328, 2003.