Getting pregnant in HIV clinical trials: women’s choice and safety needs. The experience from the ANRS12169-2LADY and ANRS12286-MOBIDIP trials

Figures & data

Table 1 Characteristics of the 66 women who became pregnant and comparison with the other women enrolled in the 2LADY and MOBIDIP trials

Before enrollment	Women who became pregnant	Women who did not became pregnant	P
WHO stage at HIV diagnosis, n (%)	/66	/215	0.02
1	19 (28.8%)	28 (13.0%)
2	14 (21.2%)	56 (26.05%)
3	27 (40.9%)	99 (46.0%)
4	6 (9.1%)	32 (14.9%)
Median CD4 nadir (IQR)	/61	/209	0.29
	112 (45–186)	90 (48–156)
Number of women who received at least one dose of hormonal contraception (medroxyprogesterone or levonorgestrel) before pregnancy or during the follow-up	13/66 (19.7%)	45/215 (20.9%)	0.80
At enrollment
Median age – year (IQR)	31 (28–34)	36 (32–41)	<0.001
Parity (including index pregnancy), n (%)	/42	not available
Primiparous	3 (7.1%)
2–3 pregnancies	26 (61.9%)
>or = 4 pregnancies	13 (31.0%)
Median parity (IQR)	3 (2–4)
Living area, n (%)	/63	/198	0.65
Urban	48 (76.2%)	161 (81.3%)
Rural	5 (7.9%)	11 (5.6%)
Semi-urban	10 (15.9%)	26 (13.1%)
Education, n (%)	/61	/203	0.10
none	15 (24.6%)	27 (13.3%)
Primary	19 (31.1%)	59 (29.1%)
Secondary	19 (31.1%)	96 (47.3%)
University	8 (13.1%)	21 (10.3%)
Marital status, n (%)	/66	/212	0.005
Single	16 (24.2%)	85 (40.1%)
Maried	31 (47.0%)	57 (26.9%)
In couple	9 (13.6%)	21 (9.9%)
Separated	7 (10.6%)	18 (8.5%)
Widow	3 (4.6%)	31 (14.6%)
Profession, n (%)	/66	/211	0.02
Student	7 (10.6%)	8 (3.8%)
Housewife	21 (31.8%)	40 (19.0%)
Unemployed	9 (13.6%)	36 (17.0%)
Active	29 (43.9%)	127 (60.2%)
Toxic use, n (%)
Tobacco	1/60 (1.7%)	0
Alcohol (occasional or regular use)	10/57 (17.5%)	32/215 (14.9%)	0.95
Serology disclosure, n (%)
With the partner	42/44 (95.5%)	67 /211 (31.7%)	<0.001
With the family	49/66 (74.2%)	169/212 (79.7%)	0.34
With friends	16/66 (24.2%)	69/212 (35.6%)	0.25
Median duration of known positive serology before enrollment – year (IQR)	/61	/203	0.04
	5 (3–6)	6 (4–7)
Co-morbidity, n (%)	7/66 (10.6%)	/215	0.58
HBV co-infection	6 (9.1%)	18 (8.4%)
diabetes	1 (1.5%)	0
Median duration of first ART before enrollment – year (IQR)	/66	/215	<0.001
	3.5 (2.1–4.8)	4.2 (2.9–5.9)
Median CD4 count (IQR)	/66	/215	0.62
	203 (103–300)	186 (93–297)
Median viral load (IQR)	/66	/215	0.56
	35359.5 cp/ml (8208–127849)	24693 cp/ml (8537–73773)
	4.5 log10 (3.9–5.1)	4.4 log10 (3.9–4.9)
During pregnancy
Median duration between enrollment and first pregnancy report – month (IQR)	/66
	15.8 (8.1–8.7)
Aymptomatic at the diagnosis of pregnancy, n (%)	84 (100%)
BMI at the beginning of pregnancy, n (%)
<18.5	4 (4.8%)
18.5–24.9	46 (54.7%)
25–29.9	21 (25%)
>or = 30	13 (15.5%)
Median CD4 count at the beginning of pregnancy (IQR)	/84
	383.5 (297.5–37.5)
VL at the beginning of pregnancy, n (%):	/84
<50 cp/ml	54 (66.6%)
50–199 cp/ml	15 (17.8%)
≥200 cp/ml	15 (17.8%)
Median of VL>200 cp/ml (IQR)	1361 (321–037)
Median CD4 count at the end of pregnancy (IQR)	/76
	408 (306–605)
VL at the end of pregnancy, n (%)	/76
<50 cp/ml	49 (64.5%)
50–199 cp/ml	13 (17.1%)
≥200 cp/ml	14 (18.4%)
Median of VL>200 cp/ml (interquartile)	1101 (300–7362)
Treatment received during pregnancy, n (%)
Lopinavir	60 (71.4%)
Darunavir	27 (32.1%)
3TC/FTC	63 (75.0%)
TDF	55 (65.5%)
ABC/DDI	21 (25.0%)

Table 2 Pregnancy and fertility rates

Study population	No women	No pregnancies	Pregnancy rate per 100 WY (95% CI)	No live-births	Fertility rate per 100 WY (95% CI)	Global fertility rate in the general population*
Cameroun	179	48	7.49	36	5.61	17.8
			(5.64–9.93)		(4.05–7.78)	Urban pop of 30-34 y:16.4
Burkina Faso	59	17	7.88	12	5.56	20.6
			(4.90–12.68)		(3.16–9.80)	Urban pop of 30-34 y:18
Senegal	47	19	10.03	12	6.34	17.2
			(6.40–15.73)		(3.60–11.16)	Urban pop of 30-34y:18.9
Total	285	84	8.03	60	5.73
			(6.48–9.94)		(4.45–7.39)

* Source: EDS Cameroun, Burkina Fasos and Senegal.^13–15

Figure 1 pregnancy incidence (in months).

Table 3 Pregnancy outcomes

Total:	84
Known outcomes:	82
Live births	60 (73.2%)
Voluntary abortion	4 (4.8%)
Extra-uterine pregnancy	2 (2.4%)
Miscarriage (<22 GW)	13 (15.8%)
Stillbirth (>22GW)	3 (3.6%)
Lost to follow-up	2
Mode of delivery, n (%):	/60
Vaginally	56 (93.3%)
Caesarean	4 (7.4%) for placenta prævia, breech presentation, condyloma and 1 non documented
Term	/59
Median term in GW (IQR)	38 (37–40)
Premature birth (term < 37 GW), n (%)	10 (16.6%)
Median term of premature births (IQR)	34 (31–34.5)
Morphologic characteristics of new-borns:
Gender F/M	38/22
Median height (IQR) cm	49 (48–51) (n = 45)
Median weight (IQR) kg	2.9 (2.6–3.2) (n = 60)
Low birth weight (<2.5 kg), n (%)	9 (15.0%)
Cranial perimeter (IQR) cm	33 (33–34) (n = 44)
Neonatal complications :	/60
Congenital abnormality, n (%)	1 (1.6%) abnormal lingual frenulum attachment
Respiratory distress, n (%)	4 (6,6%)
Death, n (%)	1 (1.9%)
Maternal complications :	/82
Death, n(%)	1 (1.2%)

Table 4 Factors associated with miscarriage/stillbirth (logistic regression) voluntary abortions excluded (n = 78)

Risk of unproductive pregnancy	Univariate analysis	Multivariate analysis
	OR [CI 95%]	OR [CI 95%]
Country
Cameroon	1
Burkina Faso	1.3 [0.3–5.1]
Senegal	1.7 [0.5–6.0]
Age at pregnancy (per year)	1.1 [0.9–1.3]	1.1 [0.9–1.3]
CD4 nadir < 200 cells/µl	0.7 [0.2–2.6]
Duration of ART (per month)	0.9 [0.6–1.2]
CD4 count < 200 cells/µl at the beginning of pregnancy	1.6 [0.3–10.4]
Viral load at the beginning of pregnancy
<50 cp/ml	1	1
50–199 cp/ml	2.7 [0.8–8.7]	2.2 [0.6–7.8]
≥200 cp/ml	1.5 [0.3–6.9]	1.0 [0.2–5.1]
Body mass index (kg/m²)
<25	1
25–29	1.2 [0.3–4.1]
≥30	1.2 [0.3–5.3]
PI received during pregnancy
LPV	1	1
DRV	3.0 [1.0–9.0]	3.1 [0.9–10.1]
NRTI received during pregnancy
TDF/3TC (or FTC)	1
ABC/ddI	0.7 [0.2–2.5]