Trial Outcomes & Findings for Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women (NCT NCT00993031)

NCT ID: NCT00993031

Last Updated: 2019-05-14

Results Overview

Number of participants with positive placental blood smear for malaria

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

389 participants

Primary outcome timeframe

Delivery

Results posted on

2019-05-14

Participant Flow

Participant milestones

Participant milestones
Measure	Without Protease Inhibitor ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	With Protease Inhibitor ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Overall Study STARTED	195	194
Overall Study Delivered	187	190
Overall Study COMPLETED	173	175
Overall Study NOT COMPLETED	22	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Without Protease Inhibitor ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	With Protease Inhibitor ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Overall Study Death	0	1
Overall Study Physician Decision	0	2
Overall Study Withdrawal by Subject	3	3
Overall Study Lost to Follow-up	19	13

Baseline Characteristics

Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Without Protease Inhibitor n=195 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	With Protease Inhibitor n=194 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Total n=389 Participants Total of all reporting groups
Age, Continuous	29.5 years STANDARD_DEVIATION 5.4 • n=93 Participants	29.0 years STANDARD_DEVIATION 5.4 • n=4 Participants	29.3 years STANDARD_DEVIATION 7.6 • n=27 Participants
Sex: Female, Male Female	195 Participants n=93 Participants	194 Participants n=4 Participants	389 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Gestational Age, wk	21.1 weeks STANDARD_DEVIATION 4.1 • n=93 Participants	21.2 weeks STANDARD_DEVIATION 4.3 • n=4 Participants	21.1 weeks STANDARD_DEVIATION 5.9 • n=27 Participants
Previous Preganancies 0	16 participants n=93 Participants	8 participants n=4 Participants	24 participants n=27 Participants
Previous Preganancies 1	20 participants n=93 Participants	25 participants n=4 Participants	45 participants n=27 Participants
Previous Preganancies ≥2	159 participants n=93 Participants	161 participants n=4 Participants	320 participants n=27 Participants
Bed Net Ownership None	85 participants n=93 Participants	85 participants n=4 Participants	170 participants n=27 Participants
Bed Net Ownership Untreated	28 participants n=93 Participants	33 participants n=4 Participants	61 participants n=27 Participants
Bed Net Ownership ITN	77 participants n=93 Participants	70 participants n=4 Participants	147 participants n=27 Participants
Bed Net Ownership Yes; unknown treatment status	5 participants n=93 Participants	5 participants n=4 Participants	10 participants n=27 Participants
Bed Net Ownership Unknown	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Receiving TMP-SMX prophylaxis at enrollment	125 participants n=93 Participants	124 participants n=4 Participants	249 participants n=27 Participants
Hemoglobin level, g/dL	10.9 g/dL STANDARD_DEVIATION 1.3 • n=93 Participants	11.0 g/dL STANDARD_DEVIATION 1.2 • n=4 Participants	10.9 g/dL STANDARD_DEVIATION 1.8 • n=27 Participants
CD4+ T-cell count	374 cells/mm3 n=93 Participants	368 cells/mm3 n=4 Participants	370.5 cells/mm3 n=27 Participants
HIV RNA load	4.3 log10 copies/mL n=93 Participants	4.1 log10 copies/mL n=4 Participants	4.1 log10 copies/mL n=27 Participants
WHO stage HIV disease 1	181 participants n=93 Participants	189 participants n=4 Participants	370 participants n=27 Participants
WHO stage HIV disease 2	13 participants n=93 Participants	5 participants n=4 Participants	18 participants n=27 Participants
WHO stage HIV disease 3	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
WHO stage HIV disease 4	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants

PRIMARY outcome

Timeframe: Delivery

Population: Placental blood smear

Number of participants with positive placental blood smear for malaria

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=158 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=158 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Prevalence of Malaria Defined as Positive Placental Blood Smear	5 participants	6 participants

PRIMARY outcome

Timeframe: Delivery

Population: Placental blood PCR

Number of participants with positive placental blood PCR for malaria

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=157 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=155 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Prevalence of Malaria Defined as Positive Placental Blood PCR	6 participants	7 participants

SECONDARY outcome

Timeframe: Delivery

Population: Some participants did not have a placental specimen taken at delivery in the hospital (e.g. deliveries that occurred at home, missed by staff error, etc)

Number of participants with positive placental RDT for malaria. Malaria rapid diagnostic tests (RDTs) assist in the diagnosis of malaria by detecting evidence of malaria parasites (antigens) in human blood. RDTs permit a reliable detection of malaria infections particularly in remote areas with limited access to good quality microscopy services.

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=157 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=155 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Placental Malaria Defined as Positive Placental RDT	6 participants	7 participants

SECONDARY outcome

Timeframe: Number of treatments given for clinical malaria based on postive blood smear from time from randomization until 24 months after delivery or cessation of breastfeeding

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=194 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=195 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk During Pregnancy	17 treatments	17 treatments

SECONDARY outcome

Timeframe: Time from randomization until 24 months postpartum or cessation of breastfeeding

Percent of evaluated participants with composite clinical outcome defined by LBW, stillbirth (intrauterine fetal demise \>20wks GA), late spontaneous abortion(miscarriage 12-20wks GA), preterm delivery(\<37wks gestation), neonatal death(death of live-born infant within first 28 days)

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=186 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=180 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Prevalence of Composite Clinical Outcome Defined by LBW, Stillbirth(Intrauterine Fetal Demise >20wks GA), Late Spontaneous Abortion(Miscarriage 12-20wks GA), Preterm Delivery(<37wks Gestation), Neonatal Death(Death of Liveborn Infant Within First 28days)	33.9 % of evaluated participants with outcome	27.8 % of evaluated participants with outcome

SECONDARY outcome

Timeframe: Delivery

Number of participants with positive placental histopathology slide for malaria

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=162 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=165 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Placental Malaria Defined Placental Histopathologic Analysis	62 participants	47 participants

SECONDARY outcome

Timeframe: Number of treatments given for clinical malaria based on postive blood smear from time from delivery until 24 months after delivery or cessation of breastfeeding

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=190 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=187 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk After Pregnancy	21 treatments	13 treatments

SECONDARY outcome

Timeframe: Time from randomization until one year follow up

Proportion of women with severe maternal Anemia (hemoglobin \< 8g/dl by hemacue or CBC) at any point during the trial in Each Treatment Group

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=195 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=194 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Number of Participants With Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group	11 Participants	11 Participants

SECONDARY outcome

Timeframe: Time from randomization until delivery

Pre-eclampsia Defined by Hypertension \> 140/90 on Two Occasions Measured \> 6 Hours Apart With ≥1+ Proteinuria on Clean Catch Urine Dipstick

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=187 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=190 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Incidence of Pre-eclampsia Defined by Hypertension > 140/90 on Two Occasions Measured > 6 Hours Apart With ≥1+ Proteinuria on Clean Catch Urine Dipstick	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Time from randomization until delivery, an average of 20 weeks

Population: Note: The above numbers differ from the numbers of participants who delivered according to the Patient Flow Overview (187 and 190, respectively) due to the inability to measure HIV RNA a small number of women at delivery, for technical or logistical reasons.

Virologic suppression was defined as plasma HIV-1 RNA 400 copies/ml or less based on the lower limit of detection of the available test.

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=170 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=178 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Number of Participants With Maternal HIV RNA Suppression of <400 Copies/mL	166 Participants	153 Participants

SECONDARY outcome

Timeframe: Time of randomization to delivery, an average of 20 weeks

CD4 cell count recovery efavirenz at delivery

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=195 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=194 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Change in Maternal CD4 Cell Counts	-7 CD4 cell count Standard Deviation .002	57 CD4 cell count Standard Deviation .002

SECONDARY outcome

Timeframe: Delivery to 48 weeks postpartum

HIV tested by DNA PCR

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=195 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=194 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Number of Participants With Maternal to Child Transmission of HIV, Measured by Infant HIV DNA PCR	0 Participants	2 Participants

SECONDARY outcome

Timeframe: delivery

Population: Note: The above numbers differ from the numbers of participants who delivered according to the Patient Flow Overview (187 and 190, respectively) due to the fact that a small number participants chose to decline this optional measurement.

antiretroviral hair concentrations (per doubling)

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=162 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=163 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
ART Levels in Hair Samples at Delivery	5.7 antiretroviral hair concentration(ng/mg) Interval 0.05 to 36.7	6.6 antiretroviral hair concentration(ng/mg) Interval 0.05 to 47.2

SECONDARY outcome

Timeframe: Randomization to one month postpartum

Outcome measures

Outcome measures
Measure	With Protease Inhibitor n=195 Participants ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Without Protease Inhibitor n=194 Participants ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Number of Participants With Grade 3 or 4 Toxicity in the Two Treatment Groups in Women	12 Participants	8 Participants

Adverse Events

Group A

Serious events: 28 serious events

Other events: 140 other events

Deaths: 0 deaths

Group B

Serious events: 32 serious events

Other events: 137 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Diane V Havlir, MD

University of California, San Francisco

Phone: 01-415-476-4082

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Group A n=194 participants at risk ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Group B n=195 participants at risk ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Infections and infestations Complicated malaria	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
General disorders Death, natural causes	1.0% 2/194 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.00% 0/195 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Blood and lymphatic system disorders Deep venous Thrombosis	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Pregnancy, puerperium and perinatal conditions Abruptio-placenta	0.52% 1/194 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.00% 0/195 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Pregnancy, puerperium and perinatal conditions Antepartum hemorrhage	1.0% 2/194 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.00% 0/195 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Gastrointestinal disorders Enteritis	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Hepatobiliary disorders Severe anemia	3.6% 7/194 • Number of events 7 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	2.6% 5/195 • Number of events 5 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Hepatobiliary disorders Neutropenia	4.6% 9/194 • Number of events 9 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	2.6% 5/195 • Number of events 5 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Hepatobiliary disorders Thrombocytopenia	1.0% 2/194 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.5% 3/195 • Number of events 3 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Pregnancy, puerperium and perinatal conditions Abdominal pain	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Pregnancy, puerperium and perinatal conditions Intra-uterine fetal death	3.1% 6/194 • Number of events 6 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	2.6% 5/195 • Number of events 5 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Pregnancy, puerperium and perinatal conditions Premature rupture of membranes	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Pregnancy, puerperium and perinatal conditions Preterm contractions	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.5% 3/195 • Number of events 3 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Respiratory, thoracic and mediastinal disorders Tuberculosis	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Hepatobiliary disorders Pyelonephritis	1.5% 3/194 • Number of events 3 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Pregnancy, puerperium and perinatal conditions Spontaneous abortion	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Renal and urinary disorders Urinary tract infection	0.52% 1/194 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.00% 0/195 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.

Measure	Group A n=194 participants at risk ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg Lopinavir/ritonavir: LPV 200mg/r 50mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	Group B n=195 participants at risk ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg
General disorders Abdominal pain	32.5% 63/194 • Number of events 84 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	23.6% 46/195 • Number of events 64 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Psychiatric disorders Altered mental status	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Hepatobiliary disorders Anemia	9.3% 18/194 • Number of events 34 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	12.3% 24/195 • Number of events 33 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Metabolism and nutrition disorders Anorexia	2.6% 5/194 • Number of events 5 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	4.1% 8/195 • Number of events 14 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
General disorders Chills	4.1% 8/194 • Number of events 8 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	2.6% 5/195 • Number of events 5 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Respiratory, thoracic and mediastinal disorders Cough	11.9% 23/194 • Number of events 33 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	9.7% 19/195 • Number of events 36 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Hepatobiliary disorders Deep vein thrombosis	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Gastrointestinal disorders Diarrhea	4.1% 8/194 • Number of events 8 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	3.1% 6/195 • Number of events 10 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
General disorders Dizziness/Lightheadedness	1.0% 2/194 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	2.1% 4/195 • Number of events 4 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Renal and urinary disorders Dysuria	1.0% 2/194 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.00% 0/195 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
General disorders Dysphagia/odynophagia	0.52% 1/194 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Respiratory, thoracic and mediastinal disorders Dyspnea/respiratory distress	2.1% 4/194 • Number of events 7 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	2.6% 5/195 • Number of events 16 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Renal and urinary disorders Elevated ALT	1.5% 3/194 • Number of events 4 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	3.1% 6/195 • Number of events 7 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Renal and urinary disorders Elevated AST	2.1% 4/194 • Number of events 4 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.00% 0/195 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Renal and urinary disorders Elevated bilirubin	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
General disorders Fatigue/malaise	17.0% 33/194 • Number of events 39 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	13.3% 26/195 • Number of events 37 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
General disorders Headache	7.7% 15/194 • Number of events 19 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	5.6% 11/195 • Number of events 13 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Blood and lymphatic system disorders Hemorrhage	0.52% 1/194 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
General disorders Nausea	2.6% 5/194 • Number of events 5 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.5% 3/195 • Number of events 3 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Psychiatric disorders Neurosensory alteration	1.0% 2/194 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 6 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Blood and lymphatic system disorders Neutropenia	29.9% 58/194 • Number of events 100 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	31.8% 62/195 • Number of events 130 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
General disorders Oral sores	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 7 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
General disorders Pain, general	7.7% 15/194 • Number of events 17 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	8.2% 16/195 • Number of events 21 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Blood and lymphatic system disorders Pallor	2.1% 4/194 • Number of events 5 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 5 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Hepatobiliary disorders Pancreatitis	0.52% 1/194 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.00% 0/195 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Pregnancy, puerperium and perinatal conditions Pre-term premature rupture of membranes	0.52% 1/194 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Skin and subcutaneous tissue disorders Pruritis	2.6% 5/194 • Number of events 7 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	2.1% 4/195 • Number of events 5 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Renal and urinary disorders Pyelonephritis	0.52% 1/194 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.5% 3/195 • Number of events 3 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Skin and subcutaneous tissue disorders Rash (non-infectious)	2.1% 4/194 • Number of events 4 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.0% 2/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Blood and lymphatic system disorders Reduced WBC count	1.0% 2/194 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	1.5% 3/195 • Number of events 3 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Nervous system disorders Seizure	0.00% 0/194 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Blood and lymphatic system disorders Serum glucose, low	0.52% 1/194 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
General disorders Temperature, elevated	5.2% 10/194 • Number of events 11 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	3.6% 7/195 • Number of events 8 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Blood and lymphatic system disorders Thrombocytopenia	9.3% 18/194 • Number of events 23 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	5.6% 11/195 • Number of events 24 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Metabolism and nutrition disorders Unintentional weight loss	1.0% 2/194 • Number of events 2 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.51% 1/195 • Number of events 1 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Renal and urinary disorders Urine Protein	21.1% 41/194 • Number of events 47 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	12.8% 25/195 • Number of events 33 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Gastrointestinal disorders Vomiting	2.1% 4/194 • Number of events 4 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	2.1% 4/195 • Number of events 4 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.
Respiratory, thoracic and mediastinal disorders Wheezing	1.0% 2/194 • Number of events 10 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.	0.00% 0/195 • Gestational age between 12 and 28 weeks at time of enrollment up to at least 1 year of follow up after delivery or until study termination.