David V Glidden1, K Rivet Amico2, Albert Y Liu3, Sybil G Hosek4, Peter L Anderson5, Susan P Buchbinder3, Vanessa McMahan6, Kenneth H Mayer7, Burns David8, Mauro Schechter9, Beatriz Grinsztejn10, Juan Guanira11, Robert M Grant12. 1. University of California, San Francisco. 2. University of Michigan, Ann Arbor. 3. Bridge HIV, San Francisco Department of Public Health, California. 4. John Stroger Hospital of Cook County, Chicago, Illinois. 5. University of Colorado, Denver, Aurora. 6. University of Washington, Seattle. 7. Fenway Health and Beth Israel Deaconess Medical Center, Boston, Massachusetts. 8. National Institute of Allergy and Infectious Diseases, Rockville, Maryland. 9. Projeto Praça Onze, Hospital Escola São Francisco de Assis and Universidade Federal do Rio de Janeiro, and. 10. Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro, Brazil. 11. Investigaciones Médicas en Salud, Lima, Peru. 12. Gladstone Institute of Virology and San Francisco AIDS Foundation, California.
Abstract
BACKGROUND: Blinded clinical trials have reported a modest and transient "start-up syndrome" with initiation of tenofovir-based pre-exposure prophylaxis (PrEP). We evaluate this phenomenon and its effect on adherence in an open-label PrEP study. METHODS: In the iPrEx open-label extension (OLE) study, an 18-month open-label, multi-site PrEP cohort taking daily oral co-formulated tenofovir/emtricitabine, we examined the prevalence and duration of PrEP-associated symptoms and their effect on adherence, assessed by drug levels in dried blood spots tested monthly for the first 3 months. RESULTS: Symptom reports peaked within the first month, with 39% reporting potentially PrEP-related symptoms compared to 22% at baseline. Symptoms largely resolved to pre-PrEP levels by 3 months.Symptoms varied substantially in frequency by study site (range in 1-month symptoms: 11% to 70%). Nongastrointestinal (GI) symptoms were not associated with adherence (odds ratio [OR] = 1.2, 95% confidence interval [CI], .4-3.7); however, GI-associated symptoms in the first 4 weeks were inversely associated with adherence at 4 weeks (OR = 0.47, 95% CI, .23-.96). Reports of GI symptoms were associated with 7% (95% CI, 4%-11%) of suboptimal adherence in this cohort. CONCLUSIONS: PrEP-associated symptoms in the open-label setting occur in a minority of users and largely resolve within 3 months. GI symptoms are associated with a modest reduction in PrEP adherence, but good adherence is possible even in the presence of frequent symptom reports. CLINICAL TRIALS REGISTRATION: Clinicaltrials.govNCT00458393.
BACKGROUND: Blinded clinical trials have reported a modest and transient "start-up syndrome" with initiation of tenofovir-based pre-exposure prophylaxis (PrEP). We evaluate this phenomenon and its effect on adherence in an open-label PrEP study. METHODS: In the iPrEx open-label extension (OLE) study, an 18-month open-label, multi-site PrEP cohort taking daily oral co-formulated tenofovir/emtricitabine, we examined the prevalence and duration of PrEP-associated symptoms and their effect on adherence, assessed by drug levels in dried blood spots tested monthly for the first 3 months. RESULTS: Symptom reports peaked within the first month, with 39% reporting potentially PrEP-related symptoms compared to 22% at baseline. Symptoms largely resolved to pre-PrEP levels by 3 months.Symptoms varied substantially in frequency by study site (range in 1-month symptoms: 11% to 70%). Nongastrointestinal (GI) symptoms were not associated with adherence (odds ratio [OR] = 1.2, 95% confidence interval [CI], .4-3.7); however, GI-associated symptoms in the first 4 weeks were inversely associated with adherence at 4 weeks (OR = 0.47, 95% CI, .23-.96). Reports of GI symptoms were associated with 7% (95% CI, 4%-11%) of suboptimal adherence in this cohort. CONCLUSIONS: PrEP-associated symptoms in the open-label setting occur in a minority of users and largely resolve within 3 months. GI symptoms are associated with a modest reduction in PrEP adherence, but good adherence is possible even in the presence of frequent symptom reports. CLINICAL TRIALS REGISTRATION: Clinicaltrials.govNCT00458393.
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