Anti-HIV Immunoglobulin in Prevention of Maternal-Fetal HIV Transmission: Pediatric AIDS Clinical Trials Group protocol 185 (PACTG)

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Accession Number
HLB00921212a

Study Type
Clinical Trial

Collection Type
Open BioLINCC Study See bottom of this webpage for request information

Study Period
1991 - 1997

NHLBI Division
DBDR

Dataset(s) Last Updated
January 3, 2018

Consent

Commercial Use Data Restrictions No

Data Restrictions Based On Area Of Research No

Commercial Use Specimen Restrictions No

Non-Genetic Use Specimen Restrictions Based On Area Of Use No

Genetic Use Of Specimens Allowed? Yes

Genetic Use Area Of Research Restrictions No

Specific Consent Restrictions
None.

Objectives

To determine if HIV hyperimmune globulin (HIVIG) given to HIV-positive pregnant women during the second and third trimester of pregnancy reduced the likelihood of maternal-fetal HIV transmission.

Background

Several studies have identified maternal, obstetrical, and infant characteristics associated with perinatal transmission of human immunodeficiency virus type 1 (HIV-1). However, these studies were conducted primarily before the widespread use of zidovudine for the prevention of perinatal transmission. Few studies have identified risk factors for transmission among HIV-1–infected women and infants who are receiving zidovudine, yet such information is critical to the development of new interventions to reduce the risk of perinatal transmission further.

Participants

A total of 501 HIV-1–infected women who were 20 to 30 weeks pregnant, who had CD4+ lymphocyte counts of no more than 500 per cubic millimeter, and who were receiving zidovudine as prescribed by their physicians. Of these, 4 were lost to follow-up before delivery, resulting in a study population of 497 women. There were 505 live-born infants, including 9 sets of twins and 487 singletons, and 1 stillborn infant.

Design

The study was a multicenter, randomized, controlled phase 3 clinical trial conducted between October 1993 and March 1997 at 53 clinical sites in the contiguous United States and Puerto Rico. Study investigators evaluated whether prophylaxis with zidovudine combined with HIV-1 hyperimmune globulin (HIVIG) at a dose of 200 mg per kilogram of body weight administered intravenously to the women each month during pregnancy and once to the neonates at birth would lower the risk of perinatal HIV-1 transmission more than would zidovudine and intravenous infusions of immune globulin without HIV-1 antibody, at a dose of 200 mg per kilogram. Detailed information on antenatal and obstetrical variables was collected during the trial, plasma and peripheral blood cells from blood draws were collected and laboratory assays were performed at several points during the women's pregnancies to determine maternal plasma levels of HIV-1 RNA, viral titers in quantitative cultures of peripheral-blood mononuclear cells, CD4+ lymphocyte counts, and quantitative HIV-1 p24 antibody levels. Isolates were retained from HIV quantitative cultures. The mother and infant were followed for up to 78 weeks post-partum and additional blood samples and clinical variables were collected. This allowed evaluation of the independent contribution of potential risk factors for perinatal transmission of HIV-1 in a population of women and infants who received zidovudine.

Conclusions

The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission (J Infect Dis 1999: 179: 567-75). There were no significant differences between the group that received HIV-1 hyperimmune globulin and the group that received intravenous immune globulin with respect to base-line maternal, obstetrical, and infant characteristics or rates of HIV-1 transmission. Since the rates of perinatal HIV-1 transmission and the clinical and laboratory characteristics were similar in the two groups, data for all women were combined in all subsequent analyses of risk factors. The maternal plasma HIV-1 RNA level was the best predictor of the risk of perinatal transmission of HIV-1. Antiretroviral therapy that reduces the HIV-1 RNA level to below 500 copies per milliliter appears to minimize the risk of perinatal transmission as well as improve the health of the women (NEJM 1999; 341:385-393).

Publications

Stiehm ER, Lambert JS, Mofenson LM, Bethel J, Whitehouse J, Nugent R, Moye J Jr, Glenn Fowler M, Mathieson BJ, Reichelderfer P, Nemo GJ, Korelitz J, Meyer WA 3rd, Sapan CV, Jimenez E, Gandia J, Scott G, O'Sullivan MJ, Kovacs A, Stek A, Shearer WT, Hammill H. Efficacy of zidovudine and human immunodeficiency virus (HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced disease: results of Pediatric AIDS Clinical Trials Group protocol 185. J Infect Dis. 1999 179:567-75.


Lambert JS, Mofenson LM, Fletcher CV, Moye J Jr, Stiehm ER, Meyer WA 3rd, Nemo GJ, Mathieson BJ, Hirsch G, Sapan CV, Cummins LM, Jimenez E, O'Neill E, Kovacs A, Stek A. Safety and pharmacokinetics of hyperimmune anti-human immunodeficiency virus (HIV) immunoglobulin administered to HIV-infected pregnant women and their newborns. Pediatric AIDS Clinical Trials Group Protocol 185 Pharmacokinetic Study Group. J Infect Dis. 1997 175:283-91.


Mofenson LM, Lambert JS, Stiehm ER, Bethel J, Meyer WA 3rd, Whitehouse J, Moye J Jr, Reichelderfer P, Harris DR, Fowler MG, Mathieson BJ, Nemo GJ. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med. 1999 341:385-93.


Lambert JS, Watts DH, Mofenson L, Stiehm ER, Harris DR, Bethel J, Whitehouse J, Jimenez E, Gandia J, Scott G, O'Sullivan MJ, Kovacs A, Stek A, Shearer WT, Hammill H, van Dyke R, Maupin R, Silio M, Fowler MG. Risk factors for preterm birth, low birth weight, and intrauterine growth retardation in infants born to HIV-infected pregnant women receiving zidovudine. Pediatric AIDS Clinical Trials Group 185 Team. AIDS. 2000 14:1389-99.


Watts DH, Lambert J, Stiehm ER, Harris DR, Bethel J, Mofenson L, Meyer WA 3rd, Mathieson B, Fowler MG, Nemo G; PACTG 185 Study Team. Progression of HIV disease among women following delivery. J Acquir Immune Defic Syndr. 2003 33:585-93.


Lambert JS, Harris DR, Stiehm ER, Moye J Jr, Fowler MG, Meyer WA 3rd, Bethel J, Mofenson LM. Performance characteristics of HIV-1 culture and HIV-1 DNA and RNA amplification assays for early diagnosis of perinatal HIV-1 infection. J Acquir Immune Defic Syndr. 2003 34:512-9.


Lambert JS, Moye J Jr, Plaeger SF, Stiehm ER, Bethel J, Mofenson LM, Mathieson B, Kagan J, Rosenblatt H, Paxton H, Suter H, Landay A. Association of selected phenotypic markers of lymphocyte activation and differentiation with perinatal human immunodeficiency virus transmission and infant infection. Clin Diagn Lab Immunol. 2005 12:622-31.

Additional Details

Subjects:

Mothers: 497

Infants: 506

Age:

 

Mother

Treatment A (HIVIG)

Treatment B (IVIG)

Total Subjects

16-20

48

52

100

21-25

65

73

138

26-30

76

68

144

31-35

43

39

82

36-40

20

10

30

40+

1

2

3

Sex:

 

Infant

Treatment A (HIVIG)

Treatment B (IVIG)

Total Subjects

Female

129

127

256

Male

130

120

250

Race:

 

Mother

Treatment A (HIVIG)

Treatment B (IVIG)

Total Subjects

Black, not Hispanic

136

122

258

Hispanic/Latino

86

85

171

Unknown Value

31

37

68

Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. Section 3 of the BioLINCC handbook describes the components of the review process

Visits (Vials):

08/30/2024

 

Plasma

Cells

Isolates

Total Vials

Mother - Labor/Delivery

4,388

877

1,329

6,594

Mother - Pre-entry

4,278

881

52

5,211

Mother - Entry

4,643

900

1,405

6,948

Mother - Infusion

4,437

837

1,366

6,640

Mother - Week 6

12

3

.

15

Mother - Week 12

3,612

753

68

4,433

Mother - Week 26

3,809

720

1,156

5,685

Mother - Week 48

3,021

588

85

3,694

Mother - Week 78

2,733

518

60

3,311

Infant - Birth

3,796

2,127

74

5,997

Infant - Week 1

19

27

.

46

Infant - Week 2

897

1,356

8

2,261

Infant - Week 6

1,332

1,583

71

2,986

Infant - Week 12

1,055

1,420

19

2,494

Infant - Week 16

1,009

1,410

9

2,428

Infant - Week 20

65

74

9

148

Infant - Week 24

1,245

1,487

35

2,767

Infant - Week 36

82

87

.

169

Infant - Week 48

1,156

1,342

1

2,499

Infant - Week 60

863

1,249

.

2,112

Infant - Week 78

57

63

.

120

Unknown

17

10

6

33

Visits (Subjects):

08/30/2024

 

Plasma

Total number of subjects

Average volume (mL) per subject

Mother - Labor/Delivery

467

4.70

Mother - Pre-entry

480

4.46

Mother - Entry

496

4.73

Mother - Infusion

437

5.09

Mother - Week 6

2

3.00

Mother - Week 12

415

4.35

Mother - Week 26

405

4.73

Mother - Week 48

340

4.45

Mother - Week 78

306

4.49

Infant - Birth

482

3.95

Infant - Week 1

7

1.36

Infant - Week 2

428

1.05

Infant - Week 6

462

1.44

Infant - Week 12

416

1.27

Infant - Week 16

397

1.28

Infant - Week 20

29

1.12

Infant - Week 24

404

1.54

Infant - Week 36

27

1.52

Infant - Week 48

371

1.56

Infant - Week 60

353

1.22

Infant - Week 78

20

1.43

Unknown

5

3.40

 

 

Cells

Total number of subjects

Average vials per subject

Mother - Labor/Delivery

439

2.00

Mother - Pre-entry

457

1.93

Mother - Entry

468

1.92

Mother - Infusion

417

2.01

Mother - Week 6

2

1.50

Mother - Week 12

400

1.88

Mother - Week 26

387

1.86

Mother - Week 48

314

1.87

Mother - Week 78

272

1.90

Infant - Birth

472

4.51

Infant - Week 1

8

3.38

Infant - Week 2

418

3.24

Infant - Week 6

445

3.56

Infant - Week 12

408

3.48

Infant - Week 16

389

3.62

Infant - Week 20

27

2.74

Infant - Week 24

398

3.74

Infant - Week 36

25

3.48

Infant - Week 48

363

3.70

Infant - Week 60

346

3.61

Infant - Week 78

18

3.50

Unknown

6

1.67

 

 

Isolates

Total number of subjects

Average vials per subject

Mother - Labor/Delivery

338

3.93

Mother - Pre-entry

13

4.00

Mother - Entry

361

3.89

Mother - Infusion

337

4.05

Mother - Week 12

18

3.78

Mother - Week 26

297

3.89

Mother - Week 48

23

3.70

Mother - Week 78

15

4.00

Infant - Birth

19

3.89

Infant - Week 2

2

4.00

Infant - Week 6

18

3.94

Infant - Week 12

5

3.80

Infant - Week 16

3

3.00

Infant - Week 20

2

4.50

Infant - Week 24

8

4.38

Infant - Week 48

1

1.00

Unknown

1

6.00

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