The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis.
Acquired Immunodeficiency Syndrome
/ drug therapy
Adult
Anti-HIV Agents
/ therapeutic use
Anti-Retroviral Agents
/ therapeutic use
CD4 Lymphocyte Count
Cardiovascular Diseases
/ drug therapy
Disease Susceptibility
Female
HIV Infections
/ drug therapy
HIV-1
Humans
Male
Middle Aged
Neoplasms
Proportional Hazards Models
Time-to-Treatment
Treatment Outcome
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
07 01 2019
07 01 2019
Historique:
received:
27
02
2018
accepted:
12
07
2018
pubmed:
23
7
2018
medline:
19
11
2019
entrez:
23
7
2018
Statut:
ppublish
Résumé
Pooled data from the SMART and START trials were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk. Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART versus immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups. Among 10156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37-5.56); SNA 1.62 (1.25-2.09); CVD 1.59 (1.07-2.37); cancer 1.93 (1.32-2.83); and death 1.80 (1.24-2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups. Treatment group differences in CD4 count and viral suppression were similar in SMART and START. Likely as a consequence, relative differences in risk of AIDS and SNA between immediate/continuous ART and deferred/intermittent ART were similar. NCT00027352 and NCT00867048.
Sections du résumé
Background
Pooled data from the SMART and START trials were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk.
Methods
Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART versus immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups.
Results
Among 10156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37-5.56); SNA 1.62 (1.25-2.09); CVD 1.59 (1.07-2.37); cancer 1.93 (1.32-2.83); and death 1.80 (1.24-2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups.
Conclusions
Treatment group differences in CD4 count and viral suppression were similar in SMART and START. Likely as a consequence, relative differences in risk of AIDS and SNA between immediate/continuous ART and deferred/intermittent ART were similar.
Clinical Trials Registration
NCT00027352 and NCT00867048.
Identifiants
pubmed: 30032171
pii: 5055761
doi: 10.1093/infdis/jiy442
pmc: PMC6306018
doi:
Substances chimiques
Anti-HIV Agents
0
Anti-Retroviral Agents
0
Banques de données
ClinicalTrials.gov
['NCT00027352', 'NCT00867048']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
254-263Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI120197
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U01 AI068641
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI046362
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068641
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI042170
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12023/23
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
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