Incentives conditioned on tenofovir levels to support PrEP adherence among young South African women: a randomized trial

Connie L Celum, Katherine Gill, Jennifer F Morton, Gabrielle Stein, Laura Myers, Katherine K Thomas, Margaret McConnell, Ariane van der Straten, Jared M Baeten, Menna Duyver, Eve Mendel, Keshani Naidoo, Jacqui Dallimore, Lubbe Wiesner, Linda-Gail Bekker, Connie L Celum, Katherine Gill, Jennifer F Morton, Gabrielle Stein, Laura Myers, Katherine K Thomas, Margaret McConnell, Ariane van der Straten, Jared M Baeten, Menna Duyver, Eve Mendel, Keshani Naidoo, Jacqui Dallimore, Lubbe Wiesner, Linda-Gail Bekker

Abstract

Introduction: HIV incidence remains high among African adolescent girls and young women (AGYW), who would benefit from pre-exposure prophylaxis (PrEP). Strategies to increase PrEP adherence and persistence need to be evaluated in African AGY, including incentives conditional on high adherence.

Methods: The 3Ps for Prevention Study was a 12-month prospective cohort of 200 women ages 16 to 25 initiating PrEP in South Africa from 2017 to 2018. Participants received retrospective feedback about drug levels at Months 1, 2 and 3; half was randomized to receive a 200 Rand shopping voucher ($13 US) at Months 2, 3 and 4, conditioned on high intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots (≥500 fmol/punch at Month 1, ≥700 fmol/punch at Months 2 and 3). The primary analysis was intention-to-treat, comparing the proportion with high PrEP adherence (≥700 fmol/punch) at Month 3 by randomized group, based on 100% efficacy among men who have sex with men.

Results: Median age of the 200 women was 19 years (interquartile range [IQR] 17, 21); 86% had a primary sexual partner. At Month 3, the mean TFV-DP level was 822 fmol/punch (SD 522) in the incentive group and 689 fmol/punch (SD 546) in the control group (p = 0.11). Forty-five (56%) of 85 women in the incentive group and 35 (41%) of 85 women in the control group had TFV-DP levels ≥700 fmol/punch (RR 1.35; 95% CI 0.98, 1.86; p = 0.067), which declined to 8% and 5% in the incentive and control groups at Month 12 (no significant difference by arm). 44% refilled PrEP without gaps, 14% had a gap of ≥3 weeks in coverage subsequently restarted PrEP and 54% accepted at the final dispensing visit at Month 9. No new HIV infections were observed after PrEP initiation.

Conclusions: Among South African AGYW initiating PrEP, drug levels indicated high PrEP adherence in almost half of women at Month 3, with a non-statistically significant higher proportion with high adherence among those in the incentive group. Over half persisted with the 12-month PrEP programme although high adherence declined after Month 3. Strategies to support PrEP adherence and persistence and longer-acting PrEP formulations are needed.

Trial registration: ClinicalTrials.gov NCT03142256.

Keywords: Africa; HIV pre-exposure prophylaxis; adherence; drug level feedback; incentives; young women.

© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

Figures

Figure 1
Figure 1
Study design. A bottle with 30 tablets for a 30 day PrEP supply was provided at enrollment, Months 1 and 2. At Months 3, 6, and 9, three bottles of 30 tablets were provided for a three month refill, Drug level feedback used semiquantitative levels and counseling messages based on high protection (TFV‐DP >500 fmol/punch for the month one sample and >700 fmol/punch for subsequent time points). The low protection group included the range from detectable (16 fmol/punch lower limit of detection to 500 fmol/punch for the month one sample and >700 fmol/punch for subsequent time points). The low protection group included the range from detectable (16 fmol/punch lower limit of detection to

Figure 2

CONSORT diagram. Participant flow of…

Figure 2

CONSORT diagram. Participant flow of women screened, enrolled and randomized in the 3P…

Figure 2
CONSORT diagram. Participant flow of women screened, enrolled and randomized in the 3P study. One woman was determined to be HIV‐infected at enrollment after her one month sample showed HIV‐1 antibodies; back testing of her enrollment sample which was positive for HIV RNA. The analysis sample includes 167 women at the month 3 visit who had a dried blood spot sample for tenofovir diphosphate levels for the primary three month adherence outcome.

Figure 3

PrEP Discontinuation by randomized group.…

Figure 3

PrEP Discontinuation by randomized group. PrEP discontinuation’ was defined as missed refill due…

Figure 3
PrEP Discontinuation by randomized group. PrEP discontinuation’ was defined as missed refill due to missed visit, or ≥21 days not taking PrEP as documented in discontinuation form. Women who missed a refill but had a subsequent visit where they accepted PrEP were considered to have restarted PrEP. If a participant missed all follow‐up visits, the visit month of discontinuation is the first visit month missed. ‘Fully persisted with PrEP’ is defined as having had enough PrEP to cover through the Month 12 exit visit.
Figure 2
Figure 2
CONSORT diagram. Participant flow of women screened, enrolled and randomized in the 3P study. One woman was determined to be HIV‐infected at enrollment after her one month sample showed HIV‐1 antibodies; back testing of her enrollment sample which was positive for HIV RNA. The analysis sample includes 167 women at the month 3 visit who had a dried blood spot sample for tenofovir diphosphate levels for the primary three month adherence outcome.
Figure 3
Figure 3
PrEP Discontinuation by randomized group. PrEP discontinuation’ was defined as missed refill due to missed visit, or ≥21 days not taking PrEP as documented in discontinuation form. Women who missed a refill but had a subsequent visit where they accepted PrEP were considered to have restarted PrEP. If a participant missed all follow‐up visits, the visit month of discontinuation is the first visit month missed. ‘Fully persisted with PrEP’ is defined as having had enough PrEP to cover through the Month 12 exit visit.

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