AzTrials
AzTrials

HIV InfectionsPhase 2NCT00109590

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

A Phase 2 study testing Didanosine, enteric-coated, Lopinavir/ritonavir and Nevirapine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in Thailand.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
HIV Infections
What is being tested?
Didanosine, enteric-coated, Lopinavir/ritonavir and Nevirapine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
175 participants
Where
7 sitesThailand
Study dates
Jun 2006to Nov 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Thailand7 sites

  • Siriraj Hospital Mahidol University CRS

    Bangkok, Bangkoknoi, 10700

  • Prapokklao Hosp. CRS

    Chanthaburi, 22000

  • Chiang Mai University Pediatrics-Obstetrics CRS

    Chiang Mai, 50200

  • Chiangrai Prachanukroh Hospital CRS

    Chiangrai, 57000

  • Chonburi Hosp. CRS

    Chon Buri, 20000

  • Phayao Provincial Hosp. CRS

    Phayao, 56000

  • Bhumibol Adulyadej Hosp. CRS

    Saimai, Bangkok, 10220

Other trials in Thailand

About this study

Official title: 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

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).

Read the 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.
Conditions
HIV Infections
Being tested
Didanosine, enteric-coated, Lopinavir/ritonavir, Nevirapine, Zidovudine
Keywords
HIV Seronegativity, Treatment Naive, Pregnancy, Perinatal Transmission, Vertical Transmission, Mother-To-Child Transmission, MTCT
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Didanosine, enteric-coatedDrug

    once daily

  • Lopinavir/ritonavirDrug

    twice daily

  • NevirapineDrug

    single-dose at the onset of labor

  • ZidovudineDrug

    twice daily

Study groups in NCT00109590
Study groupRoleWhat they receive
Arm A: LPV/r x 7dExperimentalNVP 200 mg orally, single dose at onset of labor, ZDV 300 mg orally at onset of labor, every 3 hours during labor and BID for 7 days postpartum, ddI 250 mg orally daily (if body weight <60 kg) or 400 mg orally twice 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.
Receives: Drug: Didanosine, enteric-coated; Drug: Lopinavir/ritonavir; Drug: Nevirapine; Drug: Zidovudine
Arm B: no LPV/rExperimentalNVP 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 daily (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.
Receives: Drug: Didanosine, enteric-coated; Drug: Nevirapine; Drug: Zidovudine
Arm C: LPV/r x 30dExperimentalNVP 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 daily (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.
Receives: Drug: Didanosine, enteric-coated; Drug: Lopinavir/ritonavir; Drug: Nevirapine; Drug: Zidovudine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: within 8 weeks postpartum.

  2. 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.

    Measured: at Day 10 or Week 6 postpartum.

  3. 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.

    Measured: Within 72 hours postpartum and during the first 30 days postpartum

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

    Measured: Within 72 hours postpartum and during the first 30 days postpartum

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

    Measured: Within 72 hours postpartum and during the first 30 days postpartum

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

    Measured: Within 72 hours postpartum and during the first 30 days postpartum

Secondary outcomes (6)

  1. 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 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.

    Measured: at Day 10 or Week 6 postpartum.

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

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

  3. 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.

    Measured: After start of study Treatment (postpartum)

  4. 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.

    Measured: within 72 weeks postpartum

  5. Resistance Mutations in HIV Infected Infants

    Resistance mutations as identified by consensus sequencing or OLA

    Measured: 24 weeks postpartum

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

    Measured: at 24 weeks postpartum

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 May 2005 (estimated)
  2. Study startJun 2006
  3. Primary completionOct 2008
  4. Study completionNov 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
175 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00109590
Sponsor's protocol ID
P1032
Other IDs
10137, PACTG P1032
Status last verified
Jan 2019
First submitted
29 Apr 2005
Last updated
5 Nov 2021

Publications

  • Cunningham CK, Chaix ML, Rekacewicz C, Britto P, Rouzioux C, Gelber RD, Dorenbaum A, Delfraissy JF, Bazin B, Mofenson L, Sullivan JL. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of pediatric AIDS clinical trials group protocol 316. J Infect Dis. 2002 Jul 15;186(2):181-8. doi: 10.1086/341300. Epub 2002 Jun 26.

    PubMed 12134253

  • Lyons FE, Coughlan S, Byrne CM, Hopkins SM, Hall WW, Mulcahy FM. Emergence of antiretroviral resistance in HIV-positive women receiving combination antiretroviral therapy in pregnancy. AIDS. 2005 Jan 3;19(1):63-7. doi: 10.1097/00002030-200501030-00007.

    PubMed 15627034

  • Sullivan JL. Prevention of mother-to-child transmission of HIV--what next? J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S67-72. doi: 10.1097/00126334-200309011-00010.

    PubMed 14562860

  • Thorne C, Newell ML. The safety of antiretroviral drugs in pregnancy. Expert Opin Drug Saf. 2005 Mar;4(2):323-35. doi: 10.1517/14740338.4.2.323.

    PubMed 15794723

  • Cressey TR, Van Dyke R, Jourdain G, Puthanakit T, Roongpisuthipong A, Achalapong J, Yuthavisuthi P, Prommas S, Chotivanich N, Maupin R, Smith E, Shapiro DE, Mirochnick M; IMPAACT P1032 Team. Early postpartum pharmacokinetics of lopinavir initiated intrapartum in Thai women. Antimicrob Agents Chemother. 2009 May;53(5):2189-91. doi: 10.1128/AAC.01091-08. Epub 2009 Feb 23.

    PubMed 19237646

  • Van Dyke RB, Ngo-Giang-Huong N, Shapiro DE, Frenkel L, Britto P, Roongpisuthipong A, Beck IA, Yuthavisuthi P, Prommas S, Puthanakit T, Achalapong J, Chotivanich N, Rasri W, Cressey TR, Maupin R, Mirochnick M, Jourdain G; IMPAACT P1032 Protocol Team. A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine. Clin Infect Dis. 2012 Jan 15;54(2):285-93. doi: 10.1093/cid/cir798. Epub 2011 Dec 5.

    PubMed 22144539

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Didanosine, enteric-coated, Lopinavir/ritonavir and Nevirapine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in Thailand.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). (time frame: within 8 weeks postpartum.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00109590, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in