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

Conditions

HIV Infections, Malaria

Keywords

HIV, Placental Malaria, Pregnancy, Uganda, Protease inhibitors, Trimethoprim-sulfamethoxazole, Treatment experienced

Brief summary

This study is an open-label, single site, randomized controlled trial comparing protease inhibitor (PI)-based antiretroviral therapy (ART) to non-PI based ART for HIV-infected pregnant and breastfeeding women of all CD4 cell counts at high risk of malaria. The study is designed to test the hypothesis that pregnant women receiving a PI-based ART regimen will have lower risk of placental malaria compared to pregnant women receiving a non-PI based ART regimen. The primary study endpoint of the study is placental malaria. This study also enrolls the infants of these women at the time of delivery.

Detailed description

The study site will be the Tororo district hospital campus situated in Eastern Uganda, an area of high malaria transmission. Using convenience sampling, we will enroll 500 HIV-infected pregnant women and their infants from the Tororo community. Eligible women between 12-28 weeks gestation will be randomized at enrollment to receive either a PI- based or an NNRTI-based ART regimen after stratification by gravidity (G1 versus G2+) and gestational age (\<24 weeks versus ≥ 24 weeks at enrollment). Treatment group A will receive Zidovudine 300mg + Lamivudine 150mg + Lopinavir/ritonavir 200mg/50mg. Treatment group B will receive Zidovudine 300mg + Lamivudine 150mg + Efavirenz 600mg. At enrollment, all study participants will receive a long lasting ITN and, as available, a basic care package including a safe water vessel, multivitamins and condoms, as per current standard of care for HIV-infected pregnant women in Uganda, if they have not already received these interventions from the referral site. Two ITNs will be provided for each mother-infant pair. Participants will receive all routine and acute medical care at a designated study clinic open 7 days a week from 8 a.m. to 5 p.m. If medical care is needed after hours, participants will be instructed to come to Tororo District Hospital premises (where the study clinic is located) and request that the study physician on-call be contacted. They will be followed up from the time of enrollment during pregnancy and through the cessation of breastfeeding; seen monthly for routine assessments and laboratory evaluations. Following delivery, the infants of enrolled women will be followed until 6 weeks following the cessation of breastfeeding but not beyond 58 weeks of life. Study participants will be followed closely for adverse events potentially due to study drugs and for malaria and HIV treatment outcomes. During the follow-up period, all patients presenting to the clinic with a new episode of fever will undergo standard evaluation (history, physical examination and Giemsa-stained blood smear) for the diagnosis of malaria. Women will receive the study treatment from the time of study entry and randomization (12-28 weeks gestation) until 1 week following the cessation of breastfeeding (but no longer than 1 year + 1 week postpartum). If a subject experiences a toxicity endpoint, ART will be changed to provide antiviral activity prior to delivery. Exclusive breastfeeding will be encouraged until 24 weeks postpartum which is the standard of care in Uganda. As per updated WHO guidelines, women will be encouraged to introduce food at 6 months of life and continue breastfeeding until 1 year of life. Women will be counseled to wean over the course of 1 month and continue antiretrovirals for at least 1 week following weaning. Furthermore, if an infant is found to be HIV-infected, Uganda MOH and WHO guidelines recommend the continuation of breastfeeding until 2 years of life and daily TS. All women will receive daily oral trimethoprim/sulfamethoxazole (TS) per Ugandan MOH guidelines. Per Ugandan MOH guidelines, all newborns will receive nevirapine syrup (10mg/ml) starting within 12 hours after birth for 6 weeks, daily oral TS from 6 weeks of life until 6 weeks following the cessation of breastfeeding, and their mothers will be instructed on ITN use for their infants.

Finkelstein JL, Herman HS, Plenty A, Mehta S, Natureeba P, Clark TD, Kamya MR, Ruel T, Charlebois ED, Cohan D, Havlir D, Young SL.

2020-04-259 citations

10.1093/cdn/nzaa075

Estradiol Levels Are Altered in Human Immunodeficiency Virus–Infected Pregnant Women Randomized to Efavirenz-Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy

Chloë R. McDonald, Andrea L. Conroy, Joel L. Gamble, Eszter Papp, Michael Hawkes et al. (14 authors)

Clinical Infectious Diseases2017-08-2427 citations

10.1093/cid/cix772

Viral Suppression and Retention in Care up to 5 Years After Initiation of Lifelong ART During Pregnancy (Option B+) in Rural Uganda.

Koss CA, Natureeba P, Kwarisiima D, Ogena M, Clark TD, Olwoch P, Cohan D, Okiring J, Charlebois ED, Kamya MR, Havlir DV.

2017-03-0130 citations

10.1097/qai.0000000000001228

Malaria burden in a birth cohort of HIV-exposed uninfected Ugandan infants living in a high malaria transmission setting.

Kakuru A, Natureeba P, Muhindo MK, Clark TD, Havlir DV, Cohan D, Dorsey G, Kamya MR, Ruel T.

2016-10-182 citations

10.1186/s12936-016-1568-z

Hair concentrations of antiretrovirals predict viral suppression in HIV-infected pregnant and breastfeeding Ugandan women

AIDS2015-10-273 citations

10.1097/01.aids.0000473544.84283.f1

Hair concentrations of antiretrovirals predict viral suppression in HIV-infected pregnant and breastfeeding Ugandan women.

Koss CA, Natureeba P, Mwesigwa J, Cohan D, Nzarubara B, Bacchetti P, Horng H, Clark TD, Plenty A, Ruel TD, Achan J, Charlebois ED, Kamya MR, Havlir DV, Gandhi M.

2015-04-0152 citations

10.1097/qad.0000000000000619

Efficacy and safety of lopinavir/ritonavir versus efavirenz-based antiretroviral therapy in HIV-infected pregnant Ugandan women.

Cohan D, Natureeba P, Koss CA, Plenty A, Luwedde F, Mwesigwa J, Ades V, Charlebois ED, Gandhi M, Clark TD, Nzarubara B, Achan J, Ruel T, Kamya MR, Havlir DV.

2015-01-0145 citations

10.1097/qad.0000000000000531

Household food insecurity, maternal nutritional status, and infant feeding practices among HIV-infected Ugandan women receiving combination antiretroviral therapy.

Young SL, Plenty AH, Luwedde FA, Natamba BK, Natureeba P, Achan J, Mwesigwa J, Ruel TD, Ades V, Osterbauer B, Clark TD, Dorsey G, Charlebois ED, Kamya M, Havlir DV, Cohan DL.

2014-11-0125 citations

10.1007/s10995-014-1450-y

Risk Factors for Preterm Birth Among HIV-Infected Pregnant Ugandan Women Randomized to Lopinavir/Ritonavir- or Efavirenz-Based Antiretroviral Therapy

Catherine A. Koss, Paul Natureeba, Albert Plenty, Flavia Luwedde, Julia Mwesigwa et al. (14 authors)

JAIDS Journal of Acquired Immune Deficiency Syndromes2014-07-2654 citations

10.1097/qai.0000000000000281

Lopinavir/Ritonavir-Based Antiretroviral Treatment (ART) Versus Efavirenz-Based ART for the Prevention of Malaria Among HIV-Infected Pregnant Women

Paul Natureeba, Veronica Ades, Flavia Luwedde, Julia Mwesigwa, Albert Plenty et al. (14 authors)

The Journal of Infectious Diseases2014-06-2357 citations

10.1093/infdis/jiu346

Anemia, vitamin B12, and folate statuses during pregnancy, and their association with obstetric outcomes among HIV‐infected Ugandan women receiving ART (804.8)

Julia L. Finkelstein, Albert Plenty, Saurabh Mehta, Paul Natureeba, Tamara D. Clark et al. (10 authors)

The FASEB Journal2014-04-01

10.1096/fasebj.28.1_supplement.804.8

Fitness Consequences of <i>Plasmodium falciparum pfmdr1</i> Polymorphisms Inferred from <i>Ex Vivo</i> Culture of Ugandan Parasites

Edwin Ochong, Patrick K. Tumwebaze, Oswald Byaruhanga, Bryan Greenhouse, Philip J. Rosenthal

Antimicrobial Agents and Chemotherapy2013-06-2522 citations

10.1128/aac.00161-13

Maternal nutritional status predicts adverse birth outcomes among HIV-infected rural Ugandan women receiving combination antiretroviral therapy.

Young S, Murray K, Mwesigwa J, Mwesigwa J, Natureeba P, Osterbauer B, Achan J, Arinaitwe E, Clark T, Ades V, Plenty A, Charlebois E, Ruel T, Kamya M, Havlir D, Cohan D.

2012-08-0739 citations

10.1371/journal.pone.0041934

Interventions

DRUGLopinavir/ritonavir

LPV 200mg/r 50mg

DRUGEfavirenz

600mg

DRUGZidovudine

Zidovudine 300 mg

DRUGLamivudine

Lamivudine 150 mg

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

16 Years to No maximum

Healthy volunteers

No

Inclusion criteria

1. Age \> 16 years (if \<18 years old, living independently from parents) 2. Documentation of HIV status must come from two assays. Assays include DNA PCR, HIV RNA, Western blot, or rapid HIV antibody test 3. Confirmed pregnancy by positive serum or urine pregnancy test or ultrasound 4. Estimated gestational age between 12 and 28 weeks (based on first day of last menstrual period with physical exam confirmation and ultrasound confirmation) at time of enrollment 5. Residency within 30 km of the study site 6. Willing to provide informed consent

Exclusion criteria

1. Current or prior use of HAART 2. Exposure to single-dose NVP (alone or with zidovudine or zidovudine/lamivudine or other abbreviated monotherapy or dual therapy for PMTCT) less than 24 months prior to enrollment 3. Prior dose-limited toxicity to TS within 14 days of study enrollment 4. Receipt of any contraindicated medications within 14 days of study enrollment (See Appendix III.) 5. Active tuberculosis or other WHO Stage 4 diseases 6. Screening laboratory values: 1. Hemoglobin: \<7.5 g/dL (Note: Women found to have a hemoglobin \<7.5 at screening may receive iron and folic acid and/or a blood transfusion at the physician's discretion. If a repeat hemoglobin is ≥7.5 g/dL, the woman may be considered for study inclusion.) 2. Absolute neutrophil count (ANC): \<750/mm3 3. Platelet count: \<50,000/mm3 4. ALT: \>225 U/L (\>5.0x ULN) 5. AST: \>225 U/L (\>5.0x ULN) 6. Bilirubin (total): \> 2.5x ULN 7. Creatinine: \> 1.8x ULN 7. Known cardiac conduction abnormalities or structural heart defect NOTE: A woman will be excluded from study participation during the current pregnancy if she goes into labor, experiences ruptured membranes or develops active tuberculosis or a WHO stage 4 condition following study enrollment but prior to study drug initiation.

Design outcomes

Primary

Measure	Time frame	Description
Prevalence of Malaria Defined as Positive Placental Blood Smear	Delivery	Number of participants with positive placental blood smear for malaria
Prevalence of Malaria Defined as Positive Placental Blood PCR	Delivery	Number of participants with positive placental blood PCR for malaria

Secondary

Measure	Time frame	Description
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)	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)
Placental Malaria Defined Placental Histopathologic Analysis	Delivery	Number of participants with positive placental histopathology slide for malaria
Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk After Pregnancy	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	—
Number of Participants With Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group	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
Number of Participants With Maternal HIV RNA Suppression of <400 Copies/mL	Time from randomization until delivery, an average of 20 weeks	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.
Placental Malaria Defined as Positive Placental RDT	Delivery	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.
Change in Maternal CD4 Cell Counts	Time of randomization to delivery, an average of 20 weeks	CD4 cell count recovery efavirenz at delivery
Number of Participants With Maternal to Child Transmission of HIV, Measured by Infant HIV DNA PCR	Delivery to 48 weeks postpartum	HIV tested by DNA PCR
ART Levels in Hair Samples at Delivery	delivery	antiretroviral hair concentrations (per doubling)
Number of Participants With Grade 3 or 4 Toxicity in the Two Treatment Groups in Women	Randomization to one month postpartum	—
Incidence of Pre-eclampsia Defined by Hypertension > 140/90 on Two Occasions Measured > 6 Hours Apart With ≥1+ Proteinuria on Clean Catch Urine Dipstick	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
Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk During Pregnancy	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	—

Countries

Uganda

Participant flow

Participants by arm

Arm	Count
Without Protease Inhibitor ZDV 300mg/3TC 150mg/EFV 600mg Efavirenz: 600mg Zidovudine: Zidovudine 300 mg Lamivudine: Lamivudine 150 mg	195
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	194
Total	389

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	0	1
Overall Study	Lost to Follow-up	19	13
Overall Study	Physician Decision	0	2
Overall Study	Withdrawal by Subject	3	3

Baseline characteristics

Characteristic	With Protease Inhibitor	Without Protease Inhibitor	Total
Age, Continuous	29.0 years STANDARD_DEVIATION 5.4	29.5 years STANDARD_DEVIATION 5.4	29.3 years STANDARD_DEVIATION 7.6
Bed Net Ownership ITN	70 participants	77 participants	147 participants
Bed Net Ownership None	85 participants	85 participants	170 participants
Bed Net Ownership Unknown	1 participants	0 participants	1 participants
Bed Net Ownership Untreated	33 participants	28 participants	61 participants
Bed Net Ownership Yes; unknown treatment status	5 participants	5 participants	10 participants
CD4+ T-cell count	368 cells/mm3	374 cells/mm3	370.5 cells/mm3
Gestational Age, wk	21.2 weeks STANDARD_DEVIATION 4.3	21.1 weeks STANDARD_DEVIATION 4.1	21.1 weeks STANDARD_DEVIATION 5.9
Hemoglobin level, g/dL	11.0 g/dL STANDARD_DEVIATION 1.2	10.9 g/dL STANDARD_DEVIATION 1.3	10.9 g/dL STANDARD_DEVIATION 1.8
HIV RNA load	4.1 log10 copies/mL	4.3 log10 copies/mL	4.1 log10 copies/mL
Previous Preganancies 0	8 participants	16 participants	24 participants
Previous Preganancies 1	25 participants	20 participants	45 participants
Previous Preganancies ≥2	161 participants	159 participants	320 participants
Receiving TMP-SMX prophylaxis at enrollment	124 participants	125 participants	249 participants
Sex: Female, Male Female	194 Participants	195 Participants	389 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants
WHO stage HIV disease 1	189 participants	181 participants	370 participants
WHO stage HIV disease 2	5 participants	13 participants	18 participants
WHO stage HIV disease 3	0 participants	1 participants	1 participants
WHO stage HIV disease 4	0 participants	0 participants	0 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	140 / 194	137 / 195
serious Total, serious adverse events	28 / 194	32 / 195

Outcome results

Primary

Prevalence of Malaria Defined as Positive Placental Blood PCR

Number of participants with positive placental blood PCR for malaria

Time frame: Delivery

Population: Placental blood PCR

Arm	Measure	Value (NUMBER)
With Protease Inhibitor	Prevalence of Malaria Defined as Positive Placental Blood PCR	6 participants
Without Protease Inhibitor	Prevalence of Malaria Defined as Positive Placental Blood PCR	7 participants

p-value: 0.7695% CI: [0.29, 2.46]Chi-squared

Primary

Prevalence of Malaria Defined as Positive Placental Blood Smear

Number of participants with positive placental blood smear for malaria

Time frame: Delivery

Population: Placental blood smear

Arm	Measure	Value (NUMBER)
With Protease Inhibitor	Prevalence of Malaria Defined as Positive Placental Blood Smear	5 participants
Without Protease Inhibitor	Prevalence of Malaria Defined as Positive Placental Blood Smear	6 participants

p-value: 0.7695% CI: [0.26, 2.67]Chi-squared

Secondary

ART Levels in Hair Samples at Delivery

antiretroviral hair concentrations (per doubling)

Time frame: 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.

Arm	Measure	Value (MEAN)
With Protease Inhibitor	ART Levels in Hair Samples at Delivery	5.7 antiretroviral hair concentration(ng/mg)
Without Protease Inhibitor	ART Levels in Hair Samples at Delivery	6.6 antiretroviral hair concentration(ng/mg)

Secondary

Change in Maternal CD4 Cell Counts

CD4 cell count recovery efavirenz at delivery

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

Arm	Measure	Value (MEDIAN)	Dispersion
With Protease Inhibitor	Change in Maternal CD4 Cell Counts	-7 CD4 cell count	Standard Deviation 0.002
Without Protease Inhibitor	Change in Maternal CD4 Cell Counts	57 CD4 cell count	Standard Deviation 0.002

Secondary

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

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

Time frame: Time from randomization until delivery

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
With Protease Inhibitor	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
Without Protease Inhibitor	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

Secondary

Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk After Pregnancy

Time frame: 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

Arm	Measure	Value (NUMBER)
With Protease Inhibitor	Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk After Pregnancy	21 treatments
Without Protease Inhibitor	Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk After Pregnancy	13 treatments

Secondary

Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk During Pregnancy

Time frame: 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

Arm	Measure	Value (NUMBER)
With Protease Inhibitor	Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk During Pregnancy	17 treatments
Without Protease Inhibitor	Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk During Pregnancy	17 treatments

Secondary

Number of Participants With Grade 3 or 4 Toxicity in the Two Treatment Groups in Women

Time frame: Randomization to one month postpartum

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
With Protease Inhibitor	Number of Participants With Grade 3 or 4 Toxicity in the Two Treatment Groups in Women	12 Participants
Without Protease Inhibitor	Number of Participants With Grade 3 or 4 Toxicity in the Two Treatment Groups in Women	8 Participants

Secondary

Number of Participants With Maternal HIV RNA Suppression of <400 Copies/mL

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.

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
With Protease Inhibitor	Number of Participants With Maternal HIV RNA Suppression of <400 Copies/mL	166 Participants
Without Protease Inhibitor	Number of Participants With Maternal HIV RNA Suppression of <400 Copies/mL	153 Participants

Secondary

Number of Participants With Maternal to Child Transmission of HIV, Measured by Infant HIV DNA PCR

HIV tested by DNA PCR

Time frame: Delivery to 48 weeks postpartum

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
With Protease Inhibitor	Number of Participants With Maternal to Child Transmission of HIV, Measured by Infant HIV DNA PCR	0 Participants
Without Protease Inhibitor	Number of Participants With Maternal to Child Transmission of HIV, Measured by Infant HIV DNA PCR	2 Participants

Secondary

Number of Participants With Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group

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

Time frame: Time from randomization until one year follow up

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
With Protease Inhibitor	Number of Participants With Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group	11 Participants
Without Protease Inhibitor	Number of Participants With Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group	11 Participants

Secondary

Placental Malaria Defined as Positive Placental RDT

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.

Time frame: 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)

Arm	Measure	Value (NUMBER)
With Protease Inhibitor	Placental Malaria Defined as Positive Placental RDT	6 participants
Without Protease Inhibitor	Placental Malaria Defined as Positive Placental RDT	7 participants

p-value: 0.4595% CI: [0.36, 1.59]Chi-squared

Secondary

Placental Malaria Defined Placental Histopathologic Analysis

Number of participants with positive placental histopathology slide for malaria

Time frame: Delivery

Arm	Measure	Value (NUMBER)
With Protease Inhibitor	Placental Malaria Defined Placental Histopathologic Analysis	62 participants
Without Protease Inhibitor	Placental Malaria Defined Placental Histopathologic Analysis	47 participants

p-value: 0.0695% CI: [0.98, 1.83]Chi-squared

Secondary

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)

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)

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

Arm	Measure	Value (NUMBER)
With Protease Inhibitor	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
Without Protease Inhibitor	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)	27.8 % of evaluated participants with outcome

p-value: 0.2195% CI: [0.89, 1.66]Chi-squared

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

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Prevalence of Malaria Defined as Positive Placental Blood PCR

Prevalence of Malaria Defined as Positive Placental Blood Smear

ART Levels in Hair Samples at Delivery

Change in Maternal CD4 Cell Counts

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

Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk After Pregnancy

Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk During Pregnancy

Number of Participants With Grade 3 or 4 Toxicity in the Two Treatment Groups in Women

Number of Participants With Maternal HIV RNA Suppression of <400 Copies/mL

Number of Participants With Maternal to Child Transmission of HIV, Measured by Infant HIV DNA PCR

Number of Participants With Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group

Placental Malaria Defined as Positive Placental RDT

Placental Malaria Defined Placental Histopathologic Analysis

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)