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AIDS 2010: Proof-of-concept that an
antiretroviral can prevent HIV infection
CAPRISA 008
Tenofovir Gel Implementation Trial
Good Adherence in Trial of Topical Pre-Exposure
Prophylaxis Integrated into Family Planning
Services
Dr Leila E Mansoor (PhD) *
Co-Principal Investigator
* on behalf of the CAPRISA 008 team
AIDS 2016 – Durban, South Africa – 22 July 2016
Introduction
• WHO recommended the roll-out of pre-exposure prophylaxis
(PrEP) to reduce HIV transmission in populations at substantial
risk.
• In Africa, a key target for PrEP implementation is young women,
the group at highest risk.
• However, PrEP efficacy is highly variable in this group:
 VOICE Trial: -49% (95% CI: -129 to 3) for daily oral TDF
 Botswana TDF2 trial: 75% (95% CI: 24 to 94) for daily oral TDF/FTC.
• Product effectiveness in “real-world” settings can also differ
markedly from product efficacy observed in clinical trials.
• Limited data exist, beyond clinical trials, to guide the introduction
of PrEP in health care services.
• Many young women utilize existing family planning (FP) services
– presents an opportunity for introducing PrEP as part of their
established sexual and reproductive health (SRH) services.
Study summary
• Purpose:
To assess adherence and effectiveness of topical
PrEP (tenofovir gel) integration into FP services –
while simultaneously providing post-trial tenofovir
gel access to CAPRISA 004 women
• Design:
Open-label, 2-arm, randomized controlled, noninferiority trial (conducted between 2012 – 2015)
• Population:
HIV-uninfected women who previously participated
in the CAPRISA 004 trial
• Measurements:
Demographics – Sex acts – Applicator counts –
Adherence – Clinic retention – HIV incidence –
Service preference
Intervention and control groups
Control arm:
CAPRISA trial clinics with monthly provision &
monitoring of tenofovir gel – similar to the
CAPRISA 004 clinical trial
Intervention arm: Public sector FP services with 2-3 monthly
provision & monitoring of tenofovir gel
The use of Quality Improvement (QI) methodology
to promote reliable service delivery.
Two-step approach:
QI used to strengthen FP services to be better
prepared for expansion
QI framework used to assist FP services to add
tenofovir gel provision to current SRH service
Study
consort
Eligible for
CAPRISA 008: 786
Pre-screened: 716*
(91.1%)
Screened: 448
(56.9%)
Enrolled: 382
(48.6%)
Vulindlela: 266
73 (9.3%) could not be contacted
268 (37.4%) were excluded
• 52 not interested in participation
• 51 had relocated
• 48 were working / studying
• 47 were HIV positive
• 38 did not return for screening visit
• 12 were not traceable
• 11 were pregnant or planning a
pregnancy
• 4 had died
• 5 other reason
66 (14.7%) were excluded
• 37 did not return timeously
• 20 were HIV positive
•
6 were not sexually active
•
2 were pregnant
•
1 was co-enrolled in another trial
eThekwini: 116
* This includes 3 participants who were screened for CAPRISA 008 in error ; 1 was screened out and 2 were enrolled
Study consort
…cont.
Enrolled: 382
FP service: 193
4 were excluded
• 2 were HIV positive
• 2 co-enrolled in another trial
Analysed: 189
15 did not complete the study
• 10 refused further participation
• 4 were lost to follow-up
• 1 withdrawn from study
Trial clinic: 189
6 were excluded
• 4 were HIV positive
• 1 no post-randomization follow-up
• 1 pregnant at enrolment
Analysed: 183
16 did not complete the study
• 9 refused further participations
• 3 were lost to follow-up
• 1 withdrawn from study
• 2 died
• 1 relocated
Completed study: 174 (92.1%)
Completed study:167 (91.3%)
Retention: 92.1%
Retention: 92.3%
Selected baseline characteristics
--- similar between FP service and trial clinics --Variable
FP service
(N=189)
Trial clinic
(N=183)
29.5; ±5.8; 20-44
1.6; ±1.1; 0-8
78 (41.3)
98 (51.9)
13 (6.9)
182 (96.2)
29.3; ±5.3; 22-44
1.5; ±1.0; 0-5
78 (42.6)
92 (50.3)
13 (7.1)
172 (93.9)
0.741
0.451
0.973
3; ±2.5; 1-25
6; ±6.7; 0-72
1/188 (0.5)
35/187 (18.7)
65 (34.4)
95 (50.3)
29 (15.3)
3; ±2.7; 1-20
6; ±5.9; 0-38
2/183 (1.1)
38/183 (20.8)
78 (42.6)
86 (47.0)
19 (10.4)
0.745
0.970
0.619
0.695
0.163
p-value
Socio-demographic characteristic
Age (mean;±SD; range)
Parity (mean;±SD; range)
Education level (n,%):
Didn’t complete high school
High school completed
Tertiary education initiated
Hormonal contraception (n,%) *
0.223
Sexual behavioural characteristics
Total lifetime sex partners (mean;±SD; range)
Sex acts: past 30 days (mean;±SD; range)
Anal sex: past 30 days (n/N,%)
Living with regular partner (n/N,%)
Male condom use (n,%): Always
Sometimes
Never
* Hormonal contraception includes depo-provera [222 (59.7%)], oral [75 (20.1%)], nur-isterate [56 (16.6%)], and implants [1 (0.25%)]
Quarterly retention rates
Target: 90% per annum
--- similar between FP service and trial clinics ---
Adherence, drug levels & HIV incidence
--- similar between FP service and trial clinics --FP service
(N=189)
(95% CI)
Trial clinic
(N=183)
(95% CI)
5.2 (4.7 - 5.7)
3.6 (3.2 – 4.1)
79.9% (76.7 – 83.2)
6.0 (5.5 - 6.5)
4.5 (4.0 – 5.0)
73.9% (70.7 – 77.1)
Adherence
Mean returned used applicators per month
Mean number of sex acts per month
Mean adherence [gel/(sex x2)]
Mean difference
Drug levels (N=313)
% with detectable drug levels at 12 months
Risk ratio
% with detectable drug levels when sex is
reported within 7 days
% with detectable drug levels when no recent
sex is reported
HIV incidence
HIV incidence per 100 women years
Incidence rate ratio
5.92% (1.5 to 10.6)
39.5% (32.2 -47.3)
43.6% (36.1 – 51.4)
0.91 (0.70 to 1.18)
81/139 (58.3%)
49/174 (28.2%)
3.5 (1.8 – 6.0)
3.6 (1.9 – 6.3)
0.96 (0.40 to 2.35)
Higher adherence (mean difference = 5.92% [CI: 1.5-10.6]) in
FP service clinics met the pre-defined non-inferiority criteria.
HIV incidence in an age-comparable
historical CAPRISA 004 placebo
control group
Incidence rate
(95% CI) in
CAPRISA 008
Incidence rate (95% CI) in
women of comparable age
from CAPRISA 004
Difference:
IRR ratio
(95% CI)
3.5 (2.3-5.2)
6.2 (CI 3.5-8.9)
Difference: -2.7
IRR: 0.56
Overall HIV incidence rate was 44% lower than that observed in an
age-comparable historical placebo-control group from the
CAPRISA 004 Tenofovir Gel trial
Preference for receiving HIV prevention
Private general practitioner
Public PHC/FP clinic
Mobile clinic
Doesn’t want to use study product
Missing
Other *
Total
(N=372)
N (%)
FP service
(N=189)
N (%)
Trial clinic
(N=183)
N (%)
27 (7.3)
280 (75.3)
6 (1.6)
1 (0.3)
12 (3.2)
46 (12.4)
11 (6.0)
147 (80.3)
5 (2.7)
0 (0.0)
6 (3.2)
20 (10.9)
16 (9.0)
133 (75.1)
1 (0.6)
1 (0.6)
6 (3.3)
26 (14.7)
* Other = CAPRISA Clinic (44), pharmacy (1), a place that opens on weekends (1)
In summary
• At baseline women assigned to FP service and trial clinics were
similar.
• During the study four critical markers were similar between the
FP service and trial clinics:
 Retention rates (92.1% vs 92.3%)
 Adherence – estimated as the proportion of reported sex acts covered by
two gel doses ( 79.9% vs 73.9%)
 Genital tenofovir levels at month 12 (39.5% vs 43.6%)
• Genital tenofovir was detected in 58.3% of 139 women reporting sex within 7 days but
only in 28.2% of 174 women reporting no recent sex.
 HIV incidence rates (3.5 per 100 wy vs 3.6 per 100 wy)
• HIV incidence rate was 44% lower than HIV incidence in an agecomparable historical CAPRISA 004 placebo control group (3.5
vs 6.2 per 100 wy).
• Most women (75.3%) expressed a preference for receiving HIV
prevention from FP service clinics.
Conclusion
• Integration of PrEP into FP services is feasible, acceptable
and can achieve good adherence, similar to those achieved
in clinical trial settings.
• While some of the behaviors related to PrEP may be
formulation dependent, this study provides broadly
applicable information on –
 the motivation of women to initiate PrEP,
 maintain follow-up, and
 adhere to tenofovir-containing HIV prevention in FP clinic services.
• This clinical trial evidence may be helpful to policy makers
and health care providers planning on implementing oral
PrEP scale-up.
Acknowledgements
•
Financial support:
 USAID (USA & SA) through CONRAD
 The South African Government’s Department of Science & Technology (DST)
through the Technology Innovations Agency (TIA)
 M-A-C AIDS fund through the Tides Foundation
•
Trial oversight committee:







CAPRISA: Q Abdool Karim, SS Abdool Karim, LE Mansoor
USAID (US): D Stanton, L Claypool, M Barnhart
USAID (Pretoria): A Thambinayagam, V Francis
CONRAD: J Schwartz, G Doncel
DST/TIA: S Gumbi, G Loots, M Selematsela, J Coates
M-A-C AIDS/Tides: N Mahon, A Flynn, R Burman
Gilead Sciences: J Rooney
•
Tenofovir & placebo gel: Provided by CONRAD & Gilead Sciences
•
FHI 360: K Torjesen, M Chen
•
IHI: K Mate, P Barker, M Tshabalala, N Mobisson-Etuk
•
CONRAD regulatory support: A Spagnoli