Structured treatment interruptions trial shows no benefit

According to the “autovaccination hypothesis,” re-exposure to HIV during treatment interruptions may stimulate the HIV-specific immune response and lead to low viremia after withdrawal of highly active antiretroviral treatment (HAART).

Many patients who started HAART earlier in their disease course than is currently recommended would like to discontinue, but it is unknown whether it is safe to do so.

The objectives of this study were to determine whether repeated treatment interruptions of HAART (1) stimulated the cytotoxic HIV-specific immune response and whether such stimulation correlated with low viremia off treatment, and (2) were safe with respect to clinical complications, development of viral resistance, and decline in CD4 cell counts.

A total of 133 patients at outpatient clinics of university hospitals in Switzerland and Spain received HAART. Participants had a median CD4 cell count of 740/microlitre, and undetectable viral load for a median of 21 months.

HAART was interrupted for two weeks, restarted, and continued for eight weeks. After four such cycles, treatment was indefinitely suspended 40 weeks after study entry.

HIV-specific cytotoxic T-cell responses were evaluated by interferon enzyme-linked immunospot analysis. The proportion of “responders” (viral load <5000 copies/mL) was measured at weeks 52 and 96. HIV-related diseases and CD4 cell counts were recorded.

Seventeen percent of patients (95% confidence interval, 11%-25%) were responders at week 52, and 8% at week 96. Low pre-HAART viral load and lack of rebound during weeks 0 to 40 predicted response. HIV-specific CD8+ T cells increased, but there was an inverse correlation between response and the number of spot-forming cells.

Eighty-five (64%) of 133 patients stopped therapy for at least 12 weeks, and 55 (41%) for at least 56 weeks. The median CD4 cell count decreased from 792/microlitre to 615/microlitre during the first 12 weeks without treatment, but stabilised thereafter. One patient (0.75%) developed drug resistance necessitating salvage treatment. There were no AIDS-related clinical complications.

The authors conclude, “Results of this study do not favour the autovaccination hypothesis. Treatment interruptions did not provoke clinical complications, and there was little drug resistance. Comparative trials will have to show what benefit, if any, is associated with intermittent, as opposed to continuous treatment.”

Catherine Fagard et al (for the Swiss HIV Cohort Study). A prospective trial of structured treatment interruptions in human immunodeficiency virus infection. Archives of Internal Medicine 2003;163:1220-1226.

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