Long-term follow-up of HIV seroconverters in microbicide trials – rationale, study design, and challenges in MTN-015

Figures & data

Figure 1 Examples of MTN-015 visit schedules. In Scenario 1, a participant is enrolled 3 months after seroconversion; the month 1 visit is missed. In Scenario 2, a participant begins ART prior to enrollment into MTN-015. The target dates for the visit schedule are based on the ART initiation date. In Scenario 3, a participant is enrolled 3 months after seroconversion and begins ART 18 months after seroconversion. The target dates for subsequent study visits are reset to be based on the ART initiation date.

Table 1 Summary of study procedures

	Enrollment	M1 Post-Seroconversion	M3 Post -Seroconversion	M 6/every 6 M Post-Seroconversion	W2, M 1, M 3 Post-ART Initiation	M6 and every 6 M Post-ART Initiation
Clinical
Acute Seroconversion Assessment	X
Concomitant Medications Assessment	X	X	X	X	X	X
Antiretroviral Treatment Record	▲				X	X
Physical Exam	X	X	X	X	X	X
Behavioral
Baseline Behavioral Questionnaire	X
Follow-Up Behavioral Questionnaire			X	X (M12 and M 24)	X (M 3 Post-ART Initiation)	X (M12 and M 24 Post-ART Initiation)
ART Adherence Questionnaire	▲				X (M 3)	X
Laboratory Procedures
Total Blood Volume Collected (mL)	83	72	77	77	72	77
Urine Pregnancy Test	X	▲	▲	▲	▲	▲
Sexually Transmitted Infection testing^a	X	▲	▲	X (every 12 M)	▲	X (every 12 M)
CBC, Liver and Renal Function	X		X	X	▲	X
CD4 T-Cell Count	X	X	X	X	X	X
Plasma HIV-1 RNA	X	X	X	X	X	X
HIV-1 Genotypic Resistance Test	X				▲	▲
HIV Serology	▲
PAP Smear^b	X	▲	▲	X (every 12 M)	▲	X (every 12 M)
Specimens for Storage
Vaginal Swabs	X	X	X	X	X	X
Cervicovaginal Lavage	X	X	X	X	X (M 3)	X
Plasma	X	X	X	X	X	X
Serum	X
PBMC ^b	X	X	X	X	X (W 2 and M 3)	X

▲: performed if clinically indicated.

M: Month; W: Week; ART: Antiretroviral therapy; CBC: Complete Blood Count;

^a Urine SDA for Chlamydia, GC, Syphilis Serology, Wet Mount for BV, Candida, Trichomonas

^b Performed at sites with capacity.

Table 2 Parent microbicide studies enrolling HIV-1 seroconverters to MTN-015

Parent study	Study short title	Parent study arms	Proportion eligible participants enrolled	Median time from HIV seroconversion to MTN-015 enrollment	Parent study reference
HPTN 035	Safety and effectiveness of BufferGel and PRO2000	• BufferGel, 0.5% • PRO2000 Gel • Placebo Gel • No Gel	72%	18 months	Abdool Karim, et al., 2011
MTN-003	Tenofovir-based HIV Preexposure Prophylaxis (VOICE)	• Oral tenofovir disoproxil fumarate • Oral tenofovir–emtricitabine • 1% tenofovir vaginal gel • Oral placebo • Vaginal gel placebo	72%	2 months	Marrazzo, et al., 2015
MTN-020	Safety and effectiveness of a dapivirine vaginal ring (ASPIRE)	• Dapivirine 25 mg vaginal ring • Placebo vaginal ring	71%*	NA*	Palanee-Phillips, et al., 2015

* Accrual ongoing; NA not available.