Adherence Pattern to a Daily Oral Pre-exposure Prophylaxis
Within our subcohort, participants in the 2 South African sites (Bloemfontein and Pretoria) had similar demographic and other baseline characteristics, although these characteristics differed from those of participants in Kenya (Bondo) (Table 2). Participants from Bloemfontein and Pretoria were younger (72% and 66%, respectively, ages: 18–24 years) than participants from Bondo (38%, ages: 18–24) and had more years of education (mean, 11.7 years in both Bloemfontein and Pretoria versus 8.6 years in Bondo). Marital status and number of sexual partners also differed: 74% of participants in Bondo and 4% of participants in both South African sites were married, and 49% of participants in Bondo versus 8% in Bloemfontein and 16% in Pretoria reported having more than 1 sexual partner at baseline. In addition, more participants in Bondo (56%) than in Bloemfontein (28%) and Pretoria (30%) were unsure whether any of their sexual partners had HIV. Similar proportions of participants in Pretoria (70%) and Bondo (74%) reported that they had had sex without using a condom at least once in the past 4 weeks with any sexual partner compared with a smaller proportion of participants in Bloemfontein (46%). Fewer participants in Bondo (22%) than in Bloemfontein (30%) and Pretoria (42%) reported using OCPs at enrollment to fulfill their contraceptive use requirement for participating in the study.
At the end of the trial, the majority of participants from all the 3 sites (55% in Bloemfontein, 53% in Pretoria, and 93% in Bondo) said that they did not know whether they were randomized to FTC/TDF or placebo. Among those participants in Bloemfontein (n = 21) and Pretoria (n = 22) who did postulate their randomization assignment, 77% correctly guessed that that they had been assigned FTC/TDF (Table 2). Almost all participants in Bondo (98%) and most participants in Bloemfontein and Pretoria (87% and 75%, respectively) reported liking the color of the study product, and fewer participants in Pretoria (57%) than in Bondo and Bloemfontein (both 83%) reported liking the size of the study product.
Fewer than 50 participants in the subcohort contributed 52 weeks of data because of early closure of the trial. Despite the availability of drug, 43.4% of all observed visit intervals had a composite adherence score of 0 (Table 3), and we observed only 28.5% of all visit intervals in the 2 highest composite adherence categories. There was also little evidence of participants exclusively taking drug in the day or 2 before clinic visits to give the appearance of adhering, also referred to as "white coat adherence." Of the 553 visit intervals with nonquantifiable concentrations of TFV-DP (<10,000 fmol/mL) and thus little or no long-term use, only 31 (5.6%) had TFV plasma concentrations consistent with pill taking in the 2 days before the visit (≥10 ng/mL). Similarly, in the majority of visit intervals demonstrating recent pill use (TFV concentrations of ≥10 ng/mL), the intracellular TFV-DP concentrations (≥100,000 fmol/mL) were consistent with using the study product fairly regularly throughout the interval (Table 3).
Figure 1 displays the frequencies of adherence scores by scheduled follow-up visit among participants in the subcohort who had the study product available for use during the visit interval. The use of study product seemed to decrease over time, with 35% of participants having good adherence (scores 4 and 5) at week 4 compared with 23% having good adherence at week 52. Conversely, nonuse of the study product (a score of 0) generally increased over time.
(Enlarge Image)
Figure 1.
Adherence score frequencies by scheduled follow-up visit.
Figure 1 also shows the frequencies of adherence scores by site. Participants from the 2 South Africa sites seemed to have the greatest variability in study product adherence, although participants in Bloemfontein contributed the least amount of follow-up data. Bondo had the highest percentage of participants with no evidence of study product use over time.
At the individual level, 83 participants (55%) had at least 1 study interval with drug concentrations consistent with good adherence. However, throughout their trial participation, only 18 participants (12%) had drug concentrations consistent with good adherence (scores 4 and 5; none of whom contributed a full 52 weeks of follow-up before study closure), 34 (23%) consistently had no or low drug concentrations (scores 0 and 1), 8 (5%) had intermittent but non-zero adherence over time (scores 2 or 3), and the majority (n = 90; 60%) had drug concentrations that generally fluctuated across all adherence scores.
In bivariate analyses, we found that being from the Bloemfontein site [odds ratio (OR): 2.31; 95% confidence interval (CI): 1.25 to 4.26 when pooling data from the other sites], liking the color of the pill (OR: 3.09; 95% CI: 1.30 to 7.35) and liking the size of the pill (OR: 2.10; 95% CI: 1.03 to 4.31) were significantly associated with good adherence (Table 4). We also found that using OCPs at enrollment (OR: 0.37; 95% CI: 0.20 to 0.70) and reporting having had sex without using a condom in the 4-week interval before drug measurement (OR: 0.60; 95% CI: 0.37 to 0.98) were negatively associated with good adherence. We saw a trend toward decreased adherence over time, but this was not significant in bivariate analysis (OR: 0.99 per week in study; 95% CI: 0.98 to 1.00). In multivariate analysis, being from the Bloemfontein site (OR: 2.43; 95% CI: 1.32 to 4.48) and liking the color of the pill (OR: 2.93; 95% CI: 1.18 to 7.27) remained positively associated with good adherence and using OCPs at enrollment remained negatively associated with good adherence (OR: 0.37; 95% CI: 0.18 to 0.74) (Table 4).
Results
Demographics and Baseline Characteristics
Within our subcohort, participants in the 2 South African sites (Bloemfontein and Pretoria) had similar demographic and other baseline characteristics, although these characteristics differed from those of participants in Kenya (Bondo) (Table 2). Participants from Bloemfontein and Pretoria were younger (72% and 66%, respectively, ages: 18–24 years) than participants from Bondo (38%, ages: 18–24) and had more years of education (mean, 11.7 years in both Bloemfontein and Pretoria versus 8.6 years in Bondo). Marital status and number of sexual partners also differed: 74% of participants in Bondo and 4% of participants in both South African sites were married, and 49% of participants in Bondo versus 8% in Bloemfontein and 16% in Pretoria reported having more than 1 sexual partner at baseline. In addition, more participants in Bondo (56%) than in Bloemfontein (28%) and Pretoria (30%) were unsure whether any of their sexual partners had HIV. Similar proportions of participants in Pretoria (70%) and Bondo (74%) reported that they had had sex without using a condom at least once in the past 4 weeks with any sexual partner compared with a smaller proportion of participants in Bloemfontein (46%). Fewer participants in Bondo (22%) than in Bloemfontein (30%) and Pretoria (42%) reported using OCPs at enrollment to fulfill their contraceptive use requirement for participating in the study.
Poststudy Variables
At the end of the trial, the majority of participants from all the 3 sites (55% in Bloemfontein, 53% in Pretoria, and 93% in Bondo) said that they did not know whether they were randomized to FTC/TDF or placebo. Among those participants in Bloemfontein (n = 21) and Pretoria (n = 22) who did postulate their randomization assignment, 77% correctly guessed that that they had been assigned FTC/TDF (Table 2). Almost all participants in Bondo (98%) and most participants in Bloemfontein and Pretoria (87% and 75%, respectively) reported liking the color of the study product, and fewer participants in Pretoria (57%) than in Bondo and Bloemfontein (both 83%) reported liking the size of the study product.
Overall Visit Interval Adherence
Fewer than 50 participants in the subcohort contributed 52 weeks of data because of early closure of the trial. Despite the availability of drug, 43.4% of all observed visit intervals had a composite adherence score of 0 (Table 3), and we observed only 28.5% of all visit intervals in the 2 highest composite adherence categories. There was also little evidence of participants exclusively taking drug in the day or 2 before clinic visits to give the appearance of adhering, also referred to as "white coat adherence." Of the 553 visit intervals with nonquantifiable concentrations of TFV-DP (<10,000 fmol/mL) and thus little or no long-term use, only 31 (5.6%) had TFV plasma concentrations consistent with pill taking in the 2 days before the visit (≥10 ng/mL). Similarly, in the majority of visit intervals demonstrating recent pill use (TFV concentrations of ≥10 ng/mL), the intracellular TFV-DP concentrations (≥100,000 fmol/mL) were consistent with using the study product fairly regularly throughout the interval (Table 3).
Patterns of Adherence Over Time
Figure 1 displays the frequencies of adherence scores by scheduled follow-up visit among participants in the subcohort who had the study product available for use during the visit interval. The use of study product seemed to decrease over time, with 35% of participants having good adherence (scores 4 and 5) at week 4 compared with 23% having good adherence at week 52. Conversely, nonuse of the study product (a score of 0) generally increased over time.
(Enlarge Image)
Figure 1.
Adherence score frequencies by scheduled follow-up visit.
Figure 1 also shows the frequencies of adherence scores by site. Participants from the 2 South Africa sites seemed to have the greatest variability in study product adherence, although participants in Bloemfontein contributed the least amount of follow-up data. Bondo had the highest percentage of participants with no evidence of study product use over time.
At the individual level, 83 participants (55%) had at least 1 study interval with drug concentrations consistent with good adherence. However, throughout their trial participation, only 18 participants (12%) had drug concentrations consistent with good adherence (scores 4 and 5; none of whom contributed a full 52 weeks of follow-up before study closure), 34 (23%) consistently had no or low drug concentrations (scores 0 and 1), 8 (5%) had intermittent but non-zero adherence over time (scores 2 or 3), and the majority (n = 90; 60%) had drug concentrations that generally fluctuated across all adherence scores.
Factors Associated With Adherence
In bivariate analyses, we found that being from the Bloemfontein site [odds ratio (OR): 2.31; 95% confidence interval (CI): 1.25 to 4.26 when pooling data from the other sites], liking the color of the pill (OR: 3.09; 95% CI: 1.30 to 7.35) and liking the size of the pill (OR: 2.10; 95% CI: 1.03 to 4.31) were significantly associated with good adherence (Table 4). We also found that using OCPs at enrollment (OR: 0.37; 95% CI: 0.20 to 0.70) and reporting having had sex without using a condom in the 4-week interval before drug measurement (OR: 0.60; 95% CI: 0.37 to 0.98) were negatively associated with good adherence. We saw a trend toward decreased adherence over time, but this was not significant in bivariate analysis (OR: 0.99 per week in study; 95% CI: 0.98 to 1.00). In multivariate analysis, being from the Bloemfontein site (OR: 2.43; 95% CI: 1.32 to 4.48) and liking the color of the pill (OR: 2.93; 95% CI: 1.18 to 7.27) remained positively associated with good adherence and using OCPs at enrollment remained negatively associated with good adherence (OR: 0.37; 95% CI: 0.18 to 0.74) (Table 4).
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