Interrupting a hydroxyurea-containing HAART regimen may not lead to the same degree of viral rebound as seen with other structured treatment interruptions, according to Franco Lori and colleagues at the RIGHT Institute, reporting in today's Lancet.
Three individuals who were receiving a HAART regimen that included hydroxyurea were treated for three weeks and then stoppped treatment for one week, following the pattern of the famous `Berlin' patient. Unlike the Berlin patient, the participants in Lori's study had already seroconverted and had varying viral load levels ( 16,130 copies (A), 21,845 copies (B) and 719,000 (C) copies respectively). After the first interruption, treatment was resumed for three months before another interruption, and individuals stayed off treatment until viral load rebounded above 5,000 copies.
At the second interruption, one patient maintained a viral load below 2,000 copies for nearly six months before rebound, whilst another patient experienced a substantial increase in the time to viral rebound between the second and third interruptions (going from approximately eight to forty days to reach 5,000 copies) (Patient B). The same trend was seen in the third patient (C), who had the highest baseline viral load, and by the time of the fifth interruption, time to rebound had increased to approximately 140 days. Patient B experienced swifter time to rebound at the fourth and fifth interruptions however.
On every occasion that treatment was resumed, viral load went back below the limits of detection, suggesting that structured treatment interruptions did not induce resistance, at least on this regimen.
The authors don't speculate on what contribution might be made by hydroxyurea in this study, but others have previously suggested that the drug's restrictive effect on CD4 cell proliferation may limit the number of cells available for infection by resurgent HIV when treatment stops. However, CD4 cell changes showed no consistent pattern in this study.
Further discussion of structured treatment interruptions can be found in two sections on aidsmap: Drug Holidays and HIV-specific immunity
Reference
Lori F et al. Structured treatment interruptions to control HIV-1 infection. The Lancet 355 (9200), 2000.