Perinatal Antiretroviral Intensification for PMTCT of HIV in Late Comers (PHPT-5)

PHPT-5 Second Phase: Perinatal Antiretroviral Intensification for the Prevention of Mother-to-child Transmission of HIV in Thai Women Having Received Less Than 8 Weeks of HAART During Pregnancy

The purpose is to evaluate the efficacy of maternal and infant perinatal antiretroviral prophylaxis intensification for the prevention of mother-to-child intrapartum transmission of HIV-1 in women receiving less than 8 weeks of antiretroviral prophylaxis during pregnancy.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Nevirapine, zidovudine, lamivudine

Detailed Description

Design: a multicenter, phase III, single-arm trial.

Perinatal antiretroviral intensification (study treatment) is defined as the addition to the standard of care* for mothers and infants of:

• Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum

• Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks:

  • NVP syrup 2 mg/kg every 24 hours for seven days, followed by NVP syrup 4 mg/kg every 24 hours for seven days. Newborns less than 2500 g will be administered 2mg/kg NVP syrup at each intake
  • AZT syrup 4 mg/ kg will be given every 12 hours for four weeks (preterm infants less than 30 weeks will be administered 2 mg/kg every 12 hours; preterm 30-35 weeks will receive 2 mg/kg every 12 hours for the first 2 weeks, increased to 3 mg/kg for the next 2 weeks).

  • 3TC syrup 2 mg/kg every 12 hours for four weeks.

    • The standard of care in Thailand is defined as:
• Maternal antiretroviral treatment: ZDV 300 mg, 3TC 150mg and LPV/r 400/100 twice a day starting as soon possible after 14 weeks of pregnancy + ZDV 300 mg every 3 hours during labor; this treatment may be continued, stopped or modified after delivery upon the recommendation of the internist.
• Newborn: ZDV 4 mg/kg every 12 hours for 4 weeks (ZDV dosing adjusted for premature infants).

• Study Type: Interventional
• Enrollment (Actual): 379
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10220
    • Bhumibol Adulyadej Hospital
  • Bangkok, Thailand, 10230
    • Nopparat Rajathanee Hospital
  • Chachoengsao, Thailand, 24000
    • Bhuddasothorn Hospital
  • Chiang Mai, Thailand, 50100
    • Health Promotion Center Region 10, Chiang Mai
  • Kalasin, Thailand, 46000
    • Kalasin Hospital
  • Khon Kaen, Thailand, 40000
    • Khon Kaen hospital
  • Khon Kaen, Thailand, 40000
    • Regional Health Promotion Centre 6, Khon Kaen
  • Lampang, Thailand, 52000
    • Lampang Hospital
  • Lamphun, Thailand, 51000
    • Lamphun Hospital
  • Nakhon Si Thammarat, Thailand, 80000
    • Maharaj Nakhon Si Thammarat Hospital
  • Nong Khai, Thailand, 43000
    • Nong Khai Hospital
  • Nonthaburi, Thailand, 11000
    • Pranangklao Hospital
  • Phayao, Thailand, 56000
    • Phayao Provincial Hospital
  • Phuket, Thailand, 83000
    • Vachira Phuket Hospital
  • Rayong, Thailand, 21000
    • Rayong Hospital
  • Songkhla, Thailand, 90100
    • Songkhla Hospital
  • Chantaburi
    • Chanthaburi, Chantaburi, Thailand, 22000
      • Prapokklao Hospital
  • Chiang Mai
    • Chom Thong, Chiang Mai, Thailand, 50160
      • Chomthong hospital
    • Fang, Chiang Mai, Thailand, 50110
      • Fang Hospital
    • Mae Rim, Chiang Mai, Thailand, 50180
      • Nakornping Hospital
    • San Pa Tong, Chiang Mai, Thailand, 50120
      • Sanpatong Hospital
  • Chiang Rai
    • Mae Chan, Chiang Rai, Thailand, 57110
      • Mae Chan Hospital
    • Phan, Chiang Rai, Thailand, 57120
      • Phan Hospital
  • Chiangrai
    • Chiang Rai, Chiangrai, Thailand, 57000
      • Chiangrai Prachanukroh Hospital
    • Chiang Rai, Chiangrai, Thailand, 57170
      • Wiangpapao Hospital
    • Chiang Saen, Chiangrai, Thailand, 57150
      • Chiang Saen Hospital
  • Chonburi
    • Bang Lamung, Chonburi, Thailand, 20150
      • Banglamung Hospital
    • Chon Buri, Chonburi, Thailand, 20000
      • Chonburi hospital
    • Chon Buri, Chonburi, Thailand, 20140
      • Panasnikom Hospital
  • Mahasarakam
    • Maha Sarakham, Mahasarakam, Thailand, 44000
      • Mahasarakam Hospital
  • Nakhonpathom
    • Nakhon Pathom, Nakhonpathom, Thailand, 73000
      • Nakhonpathom Hospital
  • Phayao
    • Chiang Kham, Phayao, Thailand, 56110
      • Chiang Kham Hospital
  • Pitsanuloke
    • Phitsanulok, Pitsanuloke, Thailand, 65000
      • Buddhachinaraj Hospital
  • Samutprakarn
    • Samut Prakan, Samutprakarn, Thailand, 10280
      • Samutprakarn Hospital
  • Samutsakhon
    • Samut Sakhon, Samutsakhon, Thailand, 74000
      • Samutsakhon Hospital
  • Songkla
    • Hat Yai, Songkla, Thailand, 90110
      • Hat Yai hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Eligibility. Pregnant women presenting at the prenatal clinics will be eligible if they are confirmed HIV-infected, intend to deliver and bring their infant to a study site for postnatal care for at least 6 months; at least 18 years old; and have given written informed consent to participate in the study, regardless of their CD4 cell count.

Maternal inclusion criteria:

• Evidence of HIV infection, as documented by two serology tests obtained at two different dates;

• All HIV infected pregnant women will be enrolled, either in the intervention arm or an observational study group.

  • Women more than 30 weeks gestational age at start of antiretroviral treatment will be eligible for the intervention. They will actually receive the study intervention if they present in labor after less than 8 weeks of treatment duration;
  • Women with no ANC will receive standard care and will be enrolled in an observational study group(and their infant will receive standard of care perinatal antiretroviral intensification)
  • Women with less than 30 weeks gestational age at start of treatment will receive standard care and will also be enrolled in the Observational Reference group;
• Agreement not to breastfeed;
• Consent to participate and to be followed for the duration of the study

Exclusion Criteria:

• Evidence of pre-existing fetal anomalies incompatible with life;
• Concurrent participation to any other clinical trial without prior agreement of the two study teams

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Perinatal intensification; Perinatal antiretroviral intensification (study treatment): Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum; Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks The standard of care in Thailand is defined as: Maternal: ZDV 300 mg, 3TC 150mg and LPV/r 400/100 twice a day starting as soon possible after 14 weeks of pregnancy + ZDV 300 mg every 3 hours during labor; Newborn: ZDV 4 mg/kg every 12 hours for 4 weeks (ZDV dosing adjusted for premature infants).

Drug: Nevirapine, zidovudine, lamivudine; Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum; Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks:NVP syrup 2 mg/kg every 24 hours for seven days, followed by NVP syrup 4 mg/kg every 24 hours for seven days. Newborns less than 2500 g will be administered 2mg/kg NVP syrup at each intakeAZT syrup 4 mg/ kg will be given every 12 hours for four weeks (preterm infants less than 30 weeks will be administered 2 mg/kg every 12 hours; preterm 30-35 weeks will receive 2 mg/kg every 12 hours for the first 2 weeks, increased to 3 mg/kg for the next 2 weeks).3TC syrup 2 mg/kg every 12 hours for four weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of perinatal HIV transmission	HIV DNA PCR analysis at birth, 2 weeks, 1, 2, 4 and 6 months of age	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety for women and neonates	All grade 3 and 4 clinical adverse events and abnormal laboratory values in women will be recorded and graded according to the toxicity tables developed by the DAIDS	Up to 12 Months
Pregnancy outcomes	Evaluation of the rates of live births and stillbirths, as well as birth weight, gestational age at delivery according to the results of the sonogram at first prenatal visit, newborn maturity (Ballard score).	Up to 12 Months

Collaborators and Investigators

• Sponsor: Institut de Recherche pour le Developpement
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Harvard School of Public Health (HSPH)
• Investigators: Principal Investigator: Marc Lallemant, MD, Institut de Recherche pour le Developpment

Publications and helpful links

General Publications

• Cressey TR, Punyawudho B, Le Coeur S, Jourdain G, Saenjum C, Capparelli EV, Jittayanun K, Phanomcheong S, Luvira A, Borkird T, Puangsombat A, Aarons L, Sukrakanchana PO, Urien S, Lallemant M; PHPT-5 study team. Assessment of Nevirapine Prophylactic and Therapeutic Dosing Regimens for Neonates. J Acquir Immune Defic Syndr. 2017 Aug 15;75(5):554-560. doi: 10.1097/QAI.0000000000001447.
• Lallemant Marc, Amzal Billy, Urien Saik, Sripan Patumrat, Cressey Tim R, Ngo-Giang-Huong Nicole, Rawangban Boonsong, Sabsanong Prapan, Siriwachirachai Thitiporn, Jarupanich Tapnarong, Kanjanavikai Prateep, Wanasiri Phaiboon, Koetsawang Suporn, Jourdain Gonzague, Le Cœur Sophie, for the PHPT-5 team. 2015. -"Antiretroviral Intensification to Prevent Intrapartum HIV Transmission in Late Comers". 8th IAS Conference on HIV Pathogenesis Treatment & Prevention, Vancouver, Canada, 19-22 July 2015.
• Lallemant M, Amzal B, Sripan P, Urien S, Cressey TR, Ngo-Giang-Huong N, Klinbuayaem V, Rawangban B, Sabsanong P, Siriwachirachai T, Jarupanich T, Kanjanavikai P, Wanasiri P, Koetsawang S, Jourdain G, Le Coeur S; PHPT-5 site investigators. Perinatal Antiretroviral Intensification to Prevent Intrapartum HIV Transmission When Antenatal Antiretroviral Therapy Is Initiated Less Than 8 Weeks Before Delivery. J Acquir Immune Defic Syndr. 2020 Jul 1;84(3):313-322. doi: 10.1097/QAI.0000000000002350.

Helpful Links

• PHPT-5 First Phase

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: January 10, 2012
• First Submitted That Met QC Criteria: January 12, 2012
• First Posted (Estimate): January 18, 2012

Study Record Updates

• Last Update Posted (Actual): October 22, 2021
• Last Update Submitted That Met QC Criteria: October 20, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Developing Countries; Prophylaxis; Thailand; HIV-1 infection; Mother-to-child transmission HIV-1
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine; Lamivudine; Zidovudine
• Other Study ID Numbers: PHPT-5 Second Phase; R01HD052461 (U.S. NIH Grant/Contract); R01HD056953 (U.S. NIH Grant/Contract)