Reducing the Incidence of Nevirapine Resistance Mutations in Pregnant HIV Infected Women Who Receive Anti-HIV Drugs Prior to and After Giving Birth

Phase II Study of the Pharmacokinetics of Nevirapine and the Incidence of Nevirapine Resistance Mutations in HIV-Infected Women Receiving a Single Intrapartum Dose of Nevirapine With the Concomitant Administration of Zidovudine/Didanosine or Zidovudine/Didanosine/Lopinavir/Ritonavir

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00109590

Enrollment

175

Registered

2005-05-02

Start date

2006-06-30

Completion date

2009-11-30

Last updated

2021-11-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV Infections

Keywords

HIV Seronegativity, Treatment Naive, Pregnancy, Perinatal Transmission, Vertical Transmission, Mother-To-Child Transmission, MTCT

Brief summary

The purpose of this study is to determine which of 3 different anti-HIV drug regimens given to HIV infected pregnant women during and after their pregnancies is most effective in reducing the incidence of nevirapine (NVP) resistance mutations. Blood levels of NVP and lopinavir/ritonavir (LPV/r) will also be studied. Study hypothesis: NVP resistance following single-dose NVP can be prevented with the concomitant administration of additional antiretroviral therapy (ART).

Detailed description

A single dose of nevirapine (SD-NVP) given to an HIV infected pregnant woman in labor followed by a single dose to her infant had been shown to be a simple and effective means of reducing mother-to-child transmission (MTCT) of HIV among women who had not received antiretroviral (ART) during pregnancy. However, development of NVP and other nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant virus was a concern. An optimal ART regimen that can prevent selection of resistant virus while efficiently preventing MTCT was needed. This study evaluated 3 different ART strategies for preventing the development of NVP resistance in HIV infected pregnant women and compared the incidence of NVP resistance mutations postpartum observed with each regimen to the incidence among historical controls. NVP and LPV/r pharmacokinetics (PK) were also evaluated in this study. Participants were randomly assigned to one of three study arms. All study participants received a single dose of oral NVP at the onset of labor and, oral zidovudine (ZDV) at the onset of labor, and every three hours during labor. Arm A: (LPV/r x 7d) participants received enteric-coated didanosine (ddI) and LPV/r orally twice daily beginning at the onset of labor and continuing through 7 days postpartum; oral ZDV was also taken twice daily for 7 days postpartum. Arm B: (no LPV/r) participants received enteric-coated ddI beginning at the onset of labor and continued through 30 days postpartum; oral ZDV was also taken twice daily for 30 days postpartum. Arm C : (LPV/r x 30d) participants received enteric-coated ddI and LPV/r orally twice daily beginning at the onset of labor and continued through 30 days postpartum; oral ZDV was also taken twice daily for 30 days postpartum. All women were followed for at least 24 weeks postpartum. Women with resistance mutations identified within 8 weeks postpartum were to be followed until 72 weeks postpartum to evaluate the persistence of the mutations. All infants were followed until at least 12 weeks of age. HIV-infected infants were to be followed until 24 weeks of age. There were 11 study visits for women at day 10, 21, and 30 and week 5, 6, 8, 12, 24, 36, 48, and 72. Medical history assessment, a physical exam, and blood collection occurred at all visits. Blood collection for PK studies occurred at Days 10, 21, and 30. All women were asked to complete an adherence questionnaire at Day 10; women assigned to Arms A : LPV/r x 7d and B: no LPV/r were also asked to complete an adherence questionnaire at Day 30. There were 6 study visits for infants at birth - 48 hours, day 21, week 5, 12, 16 and 24. Medical history assessment and a physical exam occurred at most visits; blood collection occurred at all visits. Data and specimens for the historical control comparison group were obtained from the PHPT-2 trial\*, in which five of the P1032 study sites had participated between 2001 and 2003. PHPT-2 was a study of the efficacy of SD-NVP to prevent MTCT among women who received ZDV after 27 weeks gestation but no postpartum ART. Criteria for inclusion in the historical comparison group included receipt of SD-NVP, a CD4 count of more than 250 cells per cubic millimeter within 30 days of screening or entry, and the availability of plasma samples at 10 days or 6 weeks post-partum. \* Lallement M, Jourdain G, Le Coeur S, et al. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med 2004; 351:217-28.

Interventions

DRUGDidanosine, enteric-coated

once daily

DRUGLopinavir/ritonavir

twice daily

DRUGNevirapine

single-dose at the onset of labor

DRUGZidovudine

twice daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

for Mothers: * HIV infected * Pregnant with a viable fetus * Between 28 and 38 weeks of pregnancy * CD4 count greater than 250 cells/mm3 within 30 days prior to study entry * Able to receive oral ART during labor * Willing to use acceptable forms of contraception while on study treatment * Able to provide written informed consent

Exclusion criteria

for Mothers: * Known allergy or hypersensitivity to ddI, LPV, NVP, ritonavir (RTV), or ZDV * Any ART other than ZDV during a previous pregnancy or the current pregnancy * Certain medications * Planning to receive additional ART during the first 8 weeks postpartum * Planning to breastfeed * Unlikely to comply with postpartum study requirements, in the opinion of the investigator * Certain abnormal laboratory values within 30 days prior to study entry

Design outcomes

Primary

Measure	Time frame	Description
Four (4) Hour Concentration Pharmacokinetic Outcome for LPV/r (C4hour ug/mL).	Within 72 hours postpartum and during the first 30 days postpartum	Data was analyzed with WinNonLin (Version 5.2, Pharsight, USA) using non-compartmental methods. The pharmacokinetic parameters were calculated using the linear-trapezoidal rule. Cpredose and C4hour at the two measurement times were compared within-subject using the Wilcoxon signed-rank test.
The Proportion of Women Who Develop One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay in Plasma (Sampling Was Done at Days 10,21,30, and Weeks 5,6, and 8 Postpartum).	within 8 weeks postpartum.	The incidence of new NVP resistance mutation in plasma HIV within 8 weeks postpartum in each randomized arm was estimated using an exact binomial confidence interval. If a resistance mutation was detected at any of the timepoints then an endpoint was met. Samples with VL \<500 copies/mL were considered free of mutations. If a resistance result was missing for reasons other than VL \<500 copies/ml (e.g.missed visit), it was conservatively imputed as resistant in the primary analysis.
The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay (OLA) in Plasma	at Day 10 or Week 6 postpartum.	The incidence of new NVP resistance mutations at day 10 or week 6 postpartum in each randomized arm. Samples with viral load \<500 copies/mL were considered free of mutations. If a resistance result was missing for reasons other than VL \<500 copies/ml it was conservatively imputed as resistant in the primary analysis.
Area Under the Curve Pharmacokinetic Outcome for LPV/r. (AUC ug*hr/mL)	Within 72 hours postpartum and during the first 30 days postpartum	Data was analyzed with WinNonLin (Version 5.2, Pharsight, USA) using non-compartmental methods. The pharmacokinetic parameters were calculated using the linear-trapezoidal rule. Cpredose and C4hour at the two measurement times were compared within-subject using the Wilcoxon signed-rank test.
Maximum Concentration Pharmacokinetic Outcome for LPV/r (Cmax ug/mL) .	Within 72 hours postpartum and during the first 30 days postpartum	Data was analyzed with WinNonLin (Version 5.2, Pharsight, USA) using non-compartmental methods. The pharmacokinetic parameters were calculated using the linear-trapezoidal rule. Cpredose and C4hour at the two measurement times were compared within-subject using the Wilcoxon signed-rank test.
Pre-dose Concentration Pharmacokinetic Outcome for LPV/r (Cpredose ug/mL).	Within 72 hours postpartum and during the first 30 days postpartum	Data was analyzed with WinNonLin (Version 5.2, Pharsight, USA) using non-compartmental methods. The pharmacokinetic parameters were calculated using the linear-trapezoidal rule. Cpredose and C4hour at the two measurement times were compared within-subject using the Wilcoxon signed-rank test.

Secondary

Measure	Time frame	Description
The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.	At Week 5 postpartum (ZDV) and at the first timepoint with viral load >=500 copies/ml after treatment discontinuation (ddI and LPV/r).	—
Number of Women With Grade >=3 Events After Start of Study Treatment	After start of study Treatment (postpartum)	Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading \> the Severity of Adult and Pediatric Adverse Events (December 2004). All grade 3 and higher signs, symptoms, and laboratory toxicities (and events of any grade that led to a change in study treatment) were included.
The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations for the Subgroup of Women With Plasma HIV RNA >= 500 Copies/ml At Entry	at Day 10 or Week 6 postpartum.	The incidence of new NVP resistance mutations at day 10 or week 6 postpartum in each randomized arm. Samples with viral load \<500 copies/mL were considered free of mutations. If a resistance result was missing for reasons other than VL \<500 copies/ml it was conservatively imputed as resistant in the primary analysis.
Proportion of Women With New NVP Resistance Mutation Within 8 Weeks Postpartum Who Had a NVP Resistance Mutation Detected at 72 Weeks Postpartum.	within 72 weeks postpartum	Resistance mutations as identified by OLA in plasma samples or PBMC at 72 weeks postpartum amongst women who had new NVP resistance mutations within 8 weeks postpatrum. These results were based on the 13 women who developed a new NVP resistance mutation in the first 8 weeks postpartum. For the primary outcome measure 1, one particpant in arm A was unavailable for follow-up after week 5 and was conservatively imputed to have developed resistance mutation.
Resistance Mutations in HIV Infected Infants	24 weeks postpartum	Resistance mutations as identified by consensus sequencing or OLA
Median HIV-1 Viral Load at 24 Weeks Postpartum in Women	at 24 weeks postpartum	—

Countries

Thailand

Participant flow

Recruitment details

Study participants were enrolled at seven IMPAACT affiliated sites in Thailand. Between June 9, 2006 and June 30, 2008, 175 participants enrolled in the study.

Pre-assignment details

The study recruited HIV infected pregnant women who were \>= 18 years of age,\>=28 to \<38 weeks gestation, who did not plan to start antiretroviral treatment within eight weeks following delivery, not planning to breastfeed and had CD4+ count \>250 cells/mm3. Women were randomized in approximately equal numbers to one of three treatment arms.

Participants by arm

Arm	Count
Arm A : LPV/r x 7d NVP 200 mg orally, single dose at onset of labor, ZDV 300 mg orally at onset of labor, every 3 hours during labor and twice daily for 7 days postpartum, ddI 250 mg orally (if body weight \<60 kg) or 400 mg orally daily (if body weight \>= 60 kg) at the onset of labor, during labor, and for 7 days postpartum, LPV/r 400/100mg orally twice daily at the onset of labor, during labor and for 7 days postpartum.	56
Arm B : no LPV/r NVP 200 mg orally, single dose at onset of labor, ZDV 300 mg orally at onset of labor, every 3 hours during labor and twice daily for 30 days postpartum, ddI 250 mg orally (if body weight \<60 kg) or 400 mg orally daily (if body weight \>= 60 kg) at the onset of labor, during labor, and for 30 days postpartum.	56
Arm C: LPV/r x 30d NVP 200 mg orally, single dose at onset of labor, ZDV 300 mg orally at onset of labor, evry 3 hours during labor and twice daily for 30 days postpartum, ddI 250 mg orally (if body weight \<60 kg) or 400 mg orally daily (if body weight \>= 60 kg) at the onset of labor, during labor, and for 30 days postpartum, LPV/r 400/100mg orally twice daily at the onset of labor, during labor and for 30 days postpartum.	57
Total	169

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Lost to Follow-up	1	0	1
Overall Study	Never Started Treatment	1	2	3

Baseline characteristics

Characteristic	Arm B : no LPV/r	Arm C: LPV/r x 30d	Arm A : LPV/r x 7d	Total
Age, Continuous	28 years STANDARD_DEVIATION 5	27 years STANDARD_DEVIATION 5	27 years STANDARD_DEVIATION 6	28 years STANDARD_DEVIATION 5
Age, Customized 18 to < 30years	35 participants	38 participants	34 participants	107 participants
Age, Customized >=30 to < 45 years	21 participants	19 participants	21 participants	61 participants
Age, Customized >= 45 years	0 participants	0 participants	1 participants	1 participants
CD4 cell count at delivery	517 cells/uL	566 cells/uL	484 cells/uL	513 cells/uL
CD4 cell count at entry	413 cells/uL	481 cells/uL	431 cells/uL	456 cells/uL
Duration of ZDV during pregnancy - At Delivery	11 weeks	10 weeks	10 weeks	10 weeks
Duration of ZDV during pregnancy - At Entry	2 weeks	2 weeks	3 weeks	3 weeks
Gestational Age at Entry	31 weeks	31 weeks	32 weeks	31 weeks
Plasma HIV-RNA at delivery	3.36 log10 copies/mL	3.48 log10 copies/mL	3.63 log10 copies/mL	3.48 log10 copies/mL
Plasma HIV RNA at entry	3.52 log10 copies/mL	3.54 log10 copies/mL	3.48 log10 copies/mL	3.49 log10 copies/mL
Sex: Female, Male Female	56 Participants	57 Participants	56 Participants	169 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	33 / 56	43 / 56	45 / 57	48 / 56	51 / 57	49 / 57
serious Total, serious adverse events	0 / 56	1 / 56	2 / 57	34 / 56	32 / 57	33 / 57

Outcome results

Primary

Area Under the Curve Pharmacokinetic Outcome for LPV/r. (AUC ug*hr/mL)

Data was analyzed with WinNonLin (Version 5.2, Pharsight, USA) using non-compartmental methods. The pharmacokinetic parameters were calculated using the linear-trapezoidal rule. Cpredose and C4hour at the two measurement times were compared within-subject using the Wilcoxon signed-rank test.

Time frame: Within 72 hours postpartum and during the first 30 days postpartum

Population: 18 women were enrolled in this sub study,PK sampling was not performed in 2 women. Of the remaining 16 women, all completed the LPV/r PK sampling within 72 hours after delivery and at day 30 postpartum and had evaluable PK within 72 hours delivery but only 14 women had evaluable PK results at day 30 postpartum due to suspected poor drug adherence.

Arm	Measure	Value (MEDIAN)
Arm A : LPV/r x 7d	Area Under the Curve Pharmacokinetic Outcome for LPV/r. (AUC ug*hr/mL)	99.7 ug*hr/mL
Arm B : no LPV/r	Area Under the Curve Pharmacokinetic Outcome for LPV/r. (AUC ug*hr/mL)	NA ug*hr/mL

Comparison: The null hypothesis was that there was no difference in within-subject Cpredose LPV/r plasma drug concentrations within 72 hours after delivery versus at 30 days postpartum.p-value: 0.009wilcoxon Signed Rank Test

Comparison: The null hypothesis was that there was no difference in within-subject C4hour LPV/r plasma drug concentrations within 72 hours after delivery versus at 30 days postpartump-value: 0.048Wilcoxon Signed Rank Test

Primary

Four (4) Hour Concentration Pharmacokinetic Outcome for LPV/r (C4hour ug/mL).

Time frame: Within 72 hours postpartum and during the first 30 days postpartum

Arm	Measure	Value (MEDIAN)
Arm A : LPV/r x 7d	Four (4) Hour Concentration Pharmacokinetic Outcome for LPV/r (C4hour ug/mL).	10.78 ug/mL
Arm B : no LPV/r	Four (4) Hour Concentration Pharmacokinetic Outcome for LPV/r (C4hour ug/mL).	12.96 ug/mL

Primary

Maximum Concentration Pharmacokinetic Outcome for LPV/r (Cmax ug/mL) .

Time frame: Within 72 hours postpartum and during the first 30 days postpartum

Arm	Measure	Value (MEDIAN)
Arm A : LPV/r x 7d	Maximum Concentration Pharmacokinetic Outcome for LPV/r (Cmax ug/mL) .	11.2 ug/mL
Arm B : no LPV/r	Maximum Concentration Pharmacokinetic Outcome for LPV/r (Cmax ug/mL) .	NA ug/mL

Primary

Pre-dose Concentration Pharmacokinetic Outcome for LPV/r (Cpredose ug/mL).

Time frame: Within 72 hours postpartum and during the first 30 days postpartum

Arm	Measure	Value (MEDIAN)
Arm A : LPV/r x 7d	Pre-dose Concentration Pharmacokinetic Outcome for LPV/r (Cpredose ug/mL).	6.08 ug/mL
Arm B : no LPV/r	Pre-dose Concentration Pharmacokinetic Outcome for LPV/r (Cpredose ug/mL).	9.17 ug/mL

Primary

The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay (OLA) in Plasma

The incidence of new NVP resistance mutations at day 10 or week 6 postpartum in each randomized arm. Samples with viral load \<500 copies/mL were considered free of mutations. If a resistance result was missing for reasons other than VL \<500 copies/ml it was conservatively imputed as resistant in the primary analysis.

Time frame: at Day 10 or Week 6 postpartum.

Population: All women who started treatment were included in an intention-to-treat analysis (according to randomized treatment assignment, regardless of compliance with the protocol)

Arm	Measure	Value (NUMBER)
Arm A : LPV/r x 7d	The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay (OLA) in Plasma	3.6 percent of participants
Arm B : no LPV/r	The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay (OLA) in Plasma	7.1 percent of participants
Arm C: LPV/r x 30d	The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay (OLA) in Plasma	5.3 percent of participants

Primary

The Proportion of Women Who Develop One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay in Plasma (Sampling Was Done at Days 10,21,30, and Weeks 5,6, and 8 Postpartum).

The incidence of new NVP resistance mutation in plasma HIV within 8 weeks postpartum in each randomized arm was estimated using an exact binomial confidence interval. If a resistance mutation was detected at any of the timepoints then an endpoint was met. Samples with VL \<500 copies/mL were considered free of mutations. If a resistance result was missing for reasons other than VL \<500 copies/ml (e.g.missed visit), it was conservatively imputed as resistant in the primary analysis.

Time frame: within 8 weeks postpartum.

Population: All women who started treatment were included in an intention-to-treat analysis.

Arm	Measure	Value (NUMBER)
Arm A : LPV/r x 7d	The Proportion of Women Who Develop One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay in Plasma (Sampling Was Done at Days 10,21,30, and Weeks 5,6, and 8 Postpartum).	7.1 percent of participants
Arm B : no LPV/r	The Proportion of Women Who Develop One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay in Plasma (Sampling Was Done at Days 10,21,30, and Weeks 5,6, and 8 Postpartum).	12.5 percent of participants
Arm C: LPV/r x 30d	The Proportion of Women Who Develop One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay in Plasma (Sampling Was Done at Days 10,21,30, and Weeks 5,6, and 8 Postpartum).	5.3 percent of participants

Secondary

Median HIV-1 Viral Load at 24 Weeks Postpartum in Women

Time frame: at 24 weeks postpartum

Population: The number of particpants included in this analyses were for those for whom viral loads were available at 24 weeeks postpartum.

Arm	Measure	Value (MEDIAN)
Arm A : LPV/r x 7d	Median HIV-1 Viral Load at 24 Weeks Postpartum in Women	4.3 log10 copies/mL
Arm B : no LPV/r	Median HIV-1 Viral Load at 24 Weeks Postpartum in Women	3.9 log10 copies/mL
Arm C: LPV/r x 30d	Median HIV-1 Viral Load at 24 Weeks Postpartum in Women	4.0 log10 copies/mL

Secondary

Number of Women With Grade >=3 Events After Start of Study Treatment

Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading \> the Severity of Adult and Pediatric Adverse Events (December 2004). All grade 3 and higher signs, symptoms, and laboratory toxicities (and events of any grade that led to a change in study treatment) were included.

Time frame: After start of study Treatment (postpartum)

Population: All women who started treatment were included in an intention-to-treat analysis.

Arm	Measure	Value (NUMBER)
Arm A : LPV/r x 7d	Number of Women With Grade >=3 Events After Start of Study Treatment	2 participants
Arm B : no LPV/r	Number of Women With Grade >=3 Events After Start of Study Treatment	0 participants
Arm C: LPV/r x 30d	Number of Women With Grade >=3 Events After Start of Study Treatment	2 participants

Secondary

Proportion of Women With New NVP Resistance Mutation Within 8 Weeks Postpartum Who Had a NVP Resistance Mutation Detected at 72 Weeks Postpartum.

Resistance mutations as identified by OLA in plasma samples or PBMC at 72 weeks postpartum amongst women who had new NVP resistance mutations within 8 weeks postpatrum. These results were based on the 13 women who developed a new NVP resistance mutation in the first 8 weeks postpartum. For the primary outcome measure 1, one particpant in arm A was unavailable for follow-up after week 5 and was conservatively imputed to have developed resistance mutation.

Time frame: within 72 weeks postpartum

Population: amongst the participants who developed resistance within 8 weeks postpartum

Arm	Measure	Group	Value (NUMBER)
Arm A : LPV/r x 7d	Proportion of Women With New NVP Resistance Mutation Within 8 Weeks Postpartum Who Had a NVP Resistance Mutation Detected at 72 Weeks Postpartum.	OLA in plasma samples	0 participants
Arm A : LPV/r x 7d	Proportion of Women With New NVP Resistance Mutation Within 8 Weeks Postpartum Who Had a NVP Resistance Mutation Detected at 72 Weeks Postpartum.	OLA in PBMC	0 participants
Arm B : no LPV/r	Proportion of Women With New NVP Resistance Mutation Within 8 Weeks Postpartum Who Had a NVP Resistance Mutation Detected at 72 Weeks Postpartum.	OLA in plasma samples	0 participants
Arm B : no LPV/r	Proportion of Women With New NVP Resistance Mutation Within 8 Weeks Postpartum Who Had a NVP Resistance Mutation Detected at 72 Weeks Postpartum.	OLA in PBMC	0 participants
Arm C: LPV/r x 30d	Proportion of Women With New NVP Resistance Mutation Within 8 Weeks Postpartum Who Had a NVP Resistance Mutation Detected at 72 Weeks Postpartum.	OLA in plasma samples	0 participants
Arm C: LPV/r x 30d	Proportion of Women With New NVP Resistance Mutation Within 8 Weeks Postpartum Who Had a NVP Resistance Mutation Detected at 72 Weeks Postpartum.	OLA in PBMC	1 participants

Secondary

Resistance Mutations in HIV Infected Infants

Resistance mutations as identified by consensus sequencing or OLA

Time frame: 24 weeks postpartum

Population: Amongst the infants who became HIV-infected.

Arm	Measure	Value (NUMBER)
Arm B : no LPV/r	Resistance Mutations in HIV Infected Infants	0 participants
Arm C: LPV/r x 30d	Resistance Mutations in HIV Infected Infants	0 participants

Secondary

The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations for the Subgroup of Women With Plasma HIV RNA >= 500 Copies/ml At Entry

Time frame: at Day 10 or Week 6 postpartum.

Population: Includes only the Subgroup of women with Plasma HIV RNA \>= 500 copies/ml at Entry and who started treatment; analyzed using the intention-to-treat principle (according to assigned treatment, regardless of compliance with the protocol).

Arm	Measure	Value (NUMBER)
Arm A : LPV/r x 7d	The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations for the Subgroup of Women With Plasma HIV RNA >= 500 Copies/ml At Entry	4.9 percent of participants
Arm B : no LPV/r	The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations for the Subgroup of Women With Plasma HIV RNA >= 500 Copies/ml At Entry	9.5 percent of participants
Arm C: LPV/r x 30d	The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations for the Subgroup of Women With Plasma HIV RNA >= 500 Copies/ml At Entry	7.0 percent of participants

Secondary

The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.

Time frame: At Week 5 postpartum (ZDV) and at the first timepoint with viral load >=500 copies/ml after treatment discontinuation (ddI and LPV/r).

Population: All women who started treatment were included in an intention-to-treat analysis

Arm	Measure	Group	Value (NUMBER)
Arm A : LPV/r x 7d	The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.	The proportion of women with new ddI resistance	0 percent of participants
Arm A : LPV/r x 7d	The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.	The proportion of women with new ZDV resistance	0 percent of participants
Arm A : LPV/r x 7d	The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.	The proportion of women with new LPV/r resistance	0 percent of participants
Arm B : no LPV/r	The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.	The proportion of women with new ddI resistance	0 percent of participants
Arm B : no LPV/r	The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.	The proportion of women with new ZDV resistance	1.78 percent of participants
Arm B : no LPV/r	The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.	The proportion of women with new LPV/r resistance	0 percent of participants
Arm C: LPV/r x 30d	The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.	The proportion of women with new ZDV resistance	0 percent of participants
Arm C: LPV/r x 30d	The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.	The proportion of women with new LPV/r resistance	0 percent of participants
Arm C: LPV/r x 30d	The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.	The proportion of women with new ddI resistance	0 percent of participants

Source: ClinicalTrials.gov · Data processed: Mar 27, 2026

Reducing the Incidence of Nevirapine Resistance Mutations in Pregnant HIV Infected Women Who Receive Anti-HIV Drugs Prior to and After Giving Birth

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Area Under the Curve Pharmacokinetic Outcome for LPV/r. (AUC ug*hr/mL)

Four (4) Hour Concentration Pharmacokinetic Outcome for LPV/r (C4hour ug/mL).

Maximum Concentration Pharmacokinetic Outcome for LPV/r (Cmax ug/mL) .

Pre-dose Concentration Pharmacokinetic Outcome for LPV/r (Cpredose ug/mL).

The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay (OLA) in Plasma

The Proportion of Women Who Develop One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay in Plasma (Sampling Was Done at Days 10,21,30, and Weeks 5,6, and 8 Postpartum).

Median HIV-1 Viral Load at 24 Weeks Postpartum in Women

Number of Women With Grade >=3 Events After Start of Study Treatment

Proportion of Women With New NVP Resistance Mutation Within 8 Weeks Postpartum Who Had a NVP Resistance Mutation Detected at 72 Weeks Postpartum.

Resistance Mutations in HIV Infected Infants

The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations for the Subgroup of Women With Plasma HIV RNA >= 500 Copies/ml At Entry

The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.