Background
All FSWs have unmet SRH needs, whether they are infected with HIV or wish to initiate PrEP
The operational implementation of HIV PrEP requires considering chronic follow-up of HIV-negative women as part of a comprehensive SRH care package
In the context of a high prevalence of hepatitis B, antiretroviral drugs (ARVs) to prevent HIV cannot be made available without making the same ARVs available to treat hepatitis B
To minimize the stigma associated with entry into care, the care of HIV-infected FSWs and the preventive follow-up of HIV-negative FSWs should not be dissociated
Follow-up from outreach activities (at prostitution sites) to community clinics is not sufficient
The high mobility of FSWs is an obstacle to continuity of care
Methods/design
Study setting
Study design and objective
Sample size and power calculation
Eligibility criteria for the PRINCESSE cohort
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Being a woman over 18 years of age
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Self-reporting as being a sex worker
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Wishing to enroll in a regular clinical follow-up
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Agreeing to participate in the study and signing the informed consent form
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Not already participating in another biomedical or behavioral study on HIV, viral hepatitis, or STIs
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Regardless of HIV status (infected or not)
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Whether or not the participant has already taken antiretrovirals
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Whether or not the participant is already followed by Aprosam
Field implementation
Healthcare offer
Time since inclusion (MO) W: week/M: month | M0 | W2 | M3 | M6 | M9 | M12 | M15 | M18 | M21 | M24 | |
---|---|---|---|---|---|---|---|---|---|---|---|
Initial screening (at inclusion) | HIV testing | ✓ | |||||||||
HBsAg testing | ✓ | ||||||||||
HIV prevention (if HIV-) | HIV testing | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||
Creatinine (if PrEP) | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||
HIV PrEP (TDF/FTC) (if eligible) | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||
At PrEP interruption (if AgHBs + or isolated HBcAb) | ALAT/ASAT (every 3 months) + HBV viral load if sign of hepatitis B reactivation | ||||||||||
HIV post-exposure prophylaxis | when needed | ||||||||||
HIV care (if HIV+) | Antiretroviral treatment | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
CD4 and viral load (if HIV+) | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||
HBV prevention (if HBsAg-) | HBsAb testing | ✓ | |||||||||
HBcAb testing | ✓ | ||||||||||
HBV vaccination (if HBsAb- et HBcAb-) | 3 × 1 doses if HIV- (M0, M1, M6), 4 × 2 doses if HIV+ (M0, M1, M2, M6) | ||||||||||
HBV care (if HBsAg+) | HBeAg testing | ✓ | |||||||||
Creatinine (if on TDF) | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||
ALT/AST/Platelets | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||
Antiretroviral treatment (TDF/FTC) (according to FIB-4 level and creatinine clearance level) | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||
HBV viral load | ✓ | ✓ | ✓ | ||||||||
STI screening and care | Syndromic STI screening | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
Systematic STI testing (Chlamydia PCR + Gonorrhea PCR + Syphilis rapid test) | ✓ | ✓ | ✓ | ||||||||
Dysplasia testing (+ treatment when necessary) | ✓ | ✓ | ✓ | ||||||||
STI treatment | when needed | ||||||||||
Pregnancy screening and contraception | Pregnancy test | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
Contraception (pills, injection or implant according to patient’s choice) | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||
Emergency pill | when needed | ||||||||||
Other | Condom and lubricating gel | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
Identification of addiction (tobacco, alcohol, drugs) and referencing when necessary | ✓ | ✓ | ✓ | ✓ |
Initial screening for HIV and hepatitis B at inclusion
Antiretroviral treatment and hepatitis B vaccination
Group of patients | HIV and AgHBs negative | HIV-positive | HIV-negative AgHBs positive Fibrose ≥ F2 Elevated ALT and HBV DNA (eligible for HBV treatment) | HIV-negative AgHBs positive Fibrose < F2 Low HBV DNA et normal ALT (not eligible for HBV treatment) |
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Hepatitis B vaccination | If not immunized (anti-HBs and anti-HBc both negatives) 3 regular doses
at M0, M1, M6 | If not immunized (anti-HBs and anti-HBc both negatives) 4 double doses
at M0, M1, M2, M6 | – | – |
Antiretroviral prescription | If creatinine clearance
≥ 60 mL/min and no contraindication TDF/FTC
(1 pill/day)
as oral PrEP | According to national guidelines As soon as possible, regardless of CD4 count Adapted regimen if HIV/HBV coinfection | If creatinine clearance
≥ 60 mL/min and no contraindication TDF/FTC
(1 pill/day)
as HBV treatment If creatinine clearance
< 60 mL/min TDF with an adapted reduced dosage (1 pill every 1, 2, 3, or 7 days depending on the rate of creatinine clearance) | If creatinine clearance
≥ 60 mL/min and no contraindication TDF/FTC
(1 pill/day)
as oral PrEP |
STI screening and care
Pregnancy screening and contraception
Other services
Specific research objectives and principal outcomes/evaluation criteria
Specific objectives | Principal outcomes | Population | Time Frame |
---|---|---|---|
SO1. Access to care, retention, and healthcare pathways | Completion rate of quarterly visits: proportion of completed study visits | All PRINCESSE participants | Up to 24 months |
SO2. Clinical, behavioral, and social evolutions | Proportion with at least one diagnosed STI (chlamydia, gonococcus, or syphilis) detected by PCR or rapid test | All PRINCESSE participants | Up to 24 months |
Occurrence of an unwanted pregnancy in the last 12 months, orally reported | All PRINCESSE participants | Up to 24 months | |
S03. Initiation, practices, and compliance with PrEP | Initiation of PrEP: proportion having initiated PrEP | PRINCESSE participants eligible for PrEP | Over 24 months |
Adherence to PrEP: proportion being adherent (measured through self-report, pill count, and drug detection in plasma) | PRINCESSE participants on PrEP | Up to 24 months | |
SO4. Comparison of HIV care (HIV+ patients of the PRINCESSE cohort vs. HIV+ patients of the NGO Aprosam not belonging to the PRINCESSE cohort) | Number of participants in HIV care at 18 months (retention) | PRINCESSE participants who are HIV-infected at baseline + HIV-infected patients of Aprosam | 18 months |
Occurrence of virological failure: proportion with two consecutive detectable viral loads | PRINCESSE participants who are HIV-infected and have initiated antiretroviral treatment + HIV-infected patients of Aprosam | Over 24 months (survival analysis) | |
S05. Prevention and care of hepatitis B | HBV vaccination rate: proportion with complete vaccination (3 doses if HIV-negative, 4 double doses if HIV-positive) at the end of the trial | PRINCESSE participants needing hepatitis B vaccination | Over 24 months |
Initiation and number of participants on TDF (retention) for patients with treatment for HBV mono-infection | PRINCESSE participants with a positive HBs-antigen and an F3-F4 fibrosis | Over 24 months | |
Proportion with an increase in transaminase level (flares) after PrEP discontinuation | PRINCESSE participants who started and stopped PrEP and with a positive HBs-antigen | Within 12 months after PrEP discontinuation | |
SO6. Unintended consequences of the PRINCESSE intervention | Number of adverse social events occurring in participants’ daily lives | All PRINCESSE participants | Over 24 months |
Qualitative evaluation of undesired social events that occurred in the daily lives of participants and non-participants | PRINCESSE participants and non-participants FSWs in the targeted area of the intervention | Over 24 months | |
SO7. Vaginal microbiota, HPV infection types, and antimicrobial STI resistance | Proportion of cervical lesions at M0 and M12 | All PRINCESSE participants | 12 months |
Proportion of high-risk HPV infection included in quadrivalent and nonavalent vaccines at genital and anal levels at M0 and M12 | All PRINCESSE participants | 12 months | |
Proportion of M. genitalium, N. gonorrheae, C. trachomatis infections at genital level at M0 and M12 Proportion of M. genitallium and N. gonorrheae antimicrobial resistances | All PRINCESSE participants | 12 months |
Data collection
Specific research objectives | |||||||
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Data collection | SO1 Access to care, retention, and healthcare pathways | SO2 Clinical, behavioral, and social evolution | SO3 Initiation, practices, and compliance with PrEP | SO4 Comparison of HIV care (PRINCESSE vs. current) | SO5 Prevention and care of hepatitis B | SO6 Unintended consequences of the PRINCESSE intervention | SO7 Vaginal microbiota, HPV infection types, and antimicrobial STI resistance |
PRINCESSE cohort | |||||||
P1. Clinical and safety data | X | X | X | X | X | X | |
P2. Socio-behavioral questionnaires | X | X | X | X | X | ||
P3. Biological data | X | X | X | X | X | ||
P4. In-depth interviews with participants | X | X | X | ||||
Additional data collection | |||||||
A1. Medical and activity records of Aprosam (PRINCESSE participants) | X | ||||||
A2. Medical records of HIV+ FSW patients (not participating in the PRINCESSE cohort) | X | ||||||
A3. In-depth interviews with members and key informants of the FSW community | X | X | |||||
A4. In-depth interviews with PRINCESSE follow-up actors | X | X | X |
Data management
Discussion
Acknowledgements
Declarations
Ethics approval and consent to participate
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Individual and written consent is collected among the PRINCESSE participants at their inclusion to be part of the PRINCESSE cohort, to receive the healthcare package, and for the collection of clinical and behavioral data by the trial medical team (P1, P3, A1);
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Specific written consent is collected among the PRINCESSE participants for each socio-behavioral questionnaire administered by an independent reviewer (P2);
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Specific written consent is collected for each face-to-face in-depth interview and focus group discussion with PRINCESSE participants: (P4) FSWs and key informants who are not participating in the PRINCESSE cohort (A3), and PRINCESSE follow-up actors (A4). Importantly, due to the COVID-19 context, the third version of the protocol includes the possibility of conducting in-depth interviews through phone calls with PRINCESSE participants (P4) and PRINCESSE follow-up actors (A4). In this context, a verbal or written agreement-in-principle is collected by peer educators, and then verbal consent is recorded by the interviewer;
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Regarding the medical and activity records of Aprosam (A2): For patients still followed up with by Aprosam, written information is given, and non-opposition is notified in the medical file; for patients no longer followed by Aprosam, a derogation from CNESVS allows for data collection, except if an opposition was previously notified.