Study
Location(s)/
Dates of Study/
Reference
|
Total Number of Pregnancies/
Total on
ARV Drugs
|
Types of ARV Regimens Compared (Numbers)
|
Association Noted Between PI-Containing or Other Multi-ARV Regimens and PTD
|
Special Notes
|
European Collaborative + Swiss Mother and Child HIV Cohort Study
1986–20001 |
3,920/896 |
Mono (573)
Multi, no PI (215)
PI-multi (108) |
YES (compared with no ARV)
Multi: 1.82 (1.13–2.92)
PI-multi: 2.60 (1.43–4.7) |
- Increase in PTD if ARV begun before pregnancy versus in third trimester
|
United States
1990–19983 |
3,266/2,123 |
Mono (1,590)
Multi (396)
PI-multi (137) |
NO (compared with mono)
Multi: 0.95 (0.60–1.48)
PI-multi: 1.45 (0.81–2.50) |
- 7 prospective clinical studies
|
European Collaborative Study
1986–20042 |
4,372/2,033 |
Mono (704)
Dual (254)
Multi (1,075) |
YES (compared with mono/dual)
Multi in pregnancy: 1.88 (1.34–2.65)
Multi prepregnancy: 2.05 (1.43–2.95) |
|
United States
1990–20024 |
2,543/not given |
Early (<25 weeks):
Mono (621)
Multi (≥2 without PI or NNRTI) (198)
Multi (with PI or NNRTI) (357)
Late (≥32 weeks):
Mono (932)
Multi (≥2 without PI or NNRTI) (258)
Multi (with PI or NNRTI) (588)
|
NO (compared with mono)
No association between any ARV and PTD |
- PTD decreased with ARV compared with no ARV
|
United States
1990–200221 |
1,337/999 |
Mono (492)
Multi (373)
PI-multi (134) |
YES (compared with other multi)
PI-multi: 1.8 (1.1–3.03) |
- PI-multi reserved for advanced disease, those who failed other multi-ARV regimens
|
Brazil, Argentina, Mexico, Bahamas
2002–200522 |
681/681 |
Mono/dual NRTI (94)
Multi-NNRTI (257)
Multi-PI (330) |
NO (compared with mono/dual NRTI)
No association between any ARV regimen and PTD |
- All on ARV for at least 28 days during pregnancy
- Preeclampsia/eclampsia, cesarean delivery, diabetes, low BMI associated with PTD
|
Meta-analysis, Europe and United States
1986–200412 |
11,224/not given |
Multi-no PI [including dual] or multi-PI (2,556) |
YES (only comparing PI with multi)
PI versus multi no PI: 1.35 (1.08–1.70) |
- 14 studies, 5 in PTD-ARV comparison
- No overall increase in PTD with antepartum ARV
- PTD increased in those on ARV pre-pregnancy and in first trimester compared with later use
|
Italy
2001–20067 |
419/366 |
Multi-PI second trimester (97)
Multi-PI third trimester (146) |
YES
Multi-PI second trimester:
2.24 (1.22–4.12)
Multi-PI third trimester:
2.81 (1.46–5.39) |
- Multivariate association also with hepatitis C
|
United States
1989–20046 |
8,793/6,228 |
Mono (2,621)
Dual (1,044)
Multi-no PI (1,781)
Multi-PI (782) |
YES (compared with dual)
Multi-PI associated with PTD 1.21 (1.04–1.40) |
- Lack of antepartum ARV also associated with PTD
- PTD and low birth weight decreased over time
|
United Kingdom, Ireland
1990–20055 |
5,009/4,445 |
Mono/dual (1,061)
Multi-NNRTI or Multi-PI (3,384) |
YES (compared with mono/dual)
Multi: 1.51 (1.19–1.93) |
- Similar increased risk with PI or no-PI multi
- No association with duration of use
|
Germany, Austria
1995–20018 |
183/183 |
Mono (77)
Dual (31)
Multi-PI (21)
Multi-NNRTI (54) |
YES (compared with mono)
Multi-PI: 3.40 (1.13–10.2) |
|
United States
2002–200716 |
777/777 |
Mono (6)
Dual (11)
Multi, no PI (202)
Multi-PI (558) |
NO (compared PI with all non-PI)
Multi-PI: 1.22 (0.70–2.12) |
- All started ARV during pregnancy
- Analyzed only spontaneous PTD
|
Swiss Mother and Child HIV Cohort Study
1985–200713 |
1,180/941 |
Mono (94)
Dual (53)
Multi (PI or no PI) (409)
Multi-PI (385) |
YES (compared with no ARV)
Multi: 2.5 (1.4–4.3) |
- No association mono/dual with PTD compared with no ARV
- No confounding by duration of ARV or maternal risk factors
|
Botswana
2006–200819 |
530/530 |
Lopinavir/ritonavir +zidovudine
+lamivudine (267)
Abacavir
+zidovudine
+lamivudine (263) |
YES
Multi-PI versus multi-NRTI: 2.03 (1.26–3.27) |
- Secondary analysis of data from randomized, controlled clinical trial of ARV begun 26–34 weeks for MTCT prevention
- All CD4-cell counts >200 cells/mm3
|
Botswana
2007–201020 |
4,347/3,659 |
ARV, regimen unspecified (70) Mono (2,473)
Multi, 91% NNRTI (1,116) |
NO
No association between multi-ART and very PTD (<32 weeks gestation) |
- Observational multi-ART before conception associated with very small for gestational age and maternal hypertension during pregnancy
|
Spain
2000–200810 |
803/739 |
Mono/dual (32)
Multi-no PI (281)
Multi-PI (426) |
NO
No association between ARV and PTD |
- Greatest PTD risk if no antepartum ARV received
|
Spain
1986–201017 |
519/371 |
Mono/dual NRTI (73)
All multi (298)
Multi-PI (178) |
NO (compared with no ARV + mono/dual)
- Spontaneous PTD not associated with multi-ARV or multi-PI before or during pregnancy
|
- Iatrogenic PTD associated with multi-ARV given in second half of pregnancy and prior PTD
|