Ask the Experts - When to Resume Therapy After STI?
Ask the Experts - When to Resume Therapy After STI?
When performing a structured treatment interruption (STI), what sort of parameters should be used to reinitiate antiretroviral therapy? The STI abstract at the 7th Conference on Retroviruses and Opportunistic Infections by Dr. Deeks stated a mean duration of 2 months. Should CD4+ cell counts (< 50 or some other arbitrary value), viral reversion (genotype or phenotype), or patients' symptoms be used to decide when to initiate therapy? What endpoints were used when deciding when to stop STI in studies already done?
Tanvir Chowdhry, MD
The duration of treatment interruption in various STI trials has varied according to study design. Where the goal has been to boost HIV-specific immune responses, treatment interruptions generally have been brief (eg, 4 weeks or until viral load is > 10,000 copies/mL). The study by Deeks and colleagues referred to in the question has since been published. In that study, patients in whom antiretroviral therapy did not result in complete suppression of viral replication underwent a planned treatment interruption for at least 12 weeks, although some remained off therapy for longer, in order to study the effects of cessation.
It must be emphasized that to date no benefit of treatment interruption has been demonstrated, either in terms of immune boosting or enhancing the response to salvage therapy in patients with multidrug-resistant HIV. Data from Deeks and others have shown re-emergence of pre-existing drug-resistant virus when treatment is resumed after an STI.
In another study presented by Deeks and associates at the 8th Conference on Retroviruses and Opportunistic Infections, viral suppression following STI was achieved in nearly all patients who added a drug from a new class (eg, a nonnucleoside reverse transcriptase inhibitor or the fusion inhibitor T-20) to their next regimen, but in few of the patients who did not add at least 1 new drug from a novel class. This would suggest that the antiretroviral efficacy of the regimen against the patient's virus is the most important consideration in achieving a successful response to salvage therapy, rather than the use of STI. Moreover, in this study patients experienced significant morbidity related to the STI, in the form of opportunistic infections.
As a result of these data, STIs should be performed very cautiously (if at all) in patients with low CD4+ cell counts (eg, < 200 cells/mm), and only under cover of prophylactic therapy for PCP, MAC, and fungal disease (if warranted). In the absence of any evidence to support the efficacy of STI as an approach to the management of salvage therapy, I would be reluctant to try this approach in anyone with a CD4+ cell count < 100 cells/mm.
When performing a structured treatment interruption (STI), what sort of parameters should be used to reinitiate antiretroviral therapy? The STI abstract at the 7th Conference on Retroviruses and Opportunistic Infections by Dr. Deeks stated a mean duration of 2 months. Should CD4+ cell counts (< 50 or some other arbitrary value), viral reversion (genotype or phenotype), or patients' symptoms be used to decide when to initiate therapy? What endpoints were used when deciding when to stop STI in studies already done?
Tanvir Chowdhry, MD
The duration of treatment interruption in various STI trials has varied according to study design. Where the goal has been to boost HIV-specific immune responses, treatment interruptions generally have been brief (eg, 4 weeks or until viral load is > 10,000 copies/mL). The study by Deeks and colleagues referred to in the question has since been published. In that study, patients in whom antiretroviral therapy did not result in complete suppression of viral replication underwent a planned treatment interruption for at least 12 weeks, although some remained off therapy for longer, in order to study the effects of cessation.
It must be emphasized that to date no benefit of treatment interruption has been demonstrated, either in terms of immune boosting or enhancing the response to salvage therapy in patients with multidrug-resistant HIV. Data from Deeks and others have shown re-emergence of pre-existing drug-resistant virus when treatment is resumed after an STI.
In another study presented by Deeks and associates at the 8th Conference on Retroviruses and Opportunistic Infections, viral suppression following STI was achieved in nearly all patients who added a drug from a new class (eg, a nonnucleoside reverse transcriptase inhibitor or the fusion inhibitor T-20) to their next regimen, but in few of the patients who did not add at least 1 new drug from a novel class. This would suggest that the antiretroviral efficacy of the regimen against the patient's virus is the most important consideration in achieving a successful response to salvage therapy, rather than the use of STI. Moreover, in this study patients experienced significant morbidity related to the STI, in the form of opportunistic infections.
As a result of these data, STIs should be performed very cautiously (if at all) in patients with low CD4+ cell counts (eg, < 200 cells/mm), and only under cover of prophylactic therapy for PCP, MAC, and fungal disease (if warranted). In the absence of any evidence to support the efficacy of STI as an approach to the management of salvage therapy, I would be reluctant to try this approach in anyone with a CD4+ cell count < 100 cells/mm.
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