Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa.
BACKGROUND
Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.


RESULTS
Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants--all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%-100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%-100%) by unannounced pill counts and 97.2% (90.6%-100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort.


CONCLUSIONS
The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.
Center for Global Health, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
Jessica E
JE
Haberer
Jared M
JM
Baeten
James
J
Campbell
Jonathan
J
Wangisi
Elly
E
Katabira
Allan
A
Ronald
Elioda
E
Tumwesigye
Christina
C
Psaros
Steven A
SA
Safren
Norma C
NC
Ware
Katherine K
KK
Thomas
Deborah
D
Donnell
Meighan
M
Krows
Lara
L
Kidoguchi
Connie
C
Celum
David R
DR
Bangsberg
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000351:Africa, Eastern / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068679:Emtricitabine; D005191:Family Characteristics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control*; D006679:HIV Seropositivity / Q000188:drug therapy*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D015999:Multivariate Analysis; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D012044:Regression Analysis; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine