Clinical trial NCT01511237: Perinatal Antiretroviral Intensification for PMTCT of HIV in Late Comers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV-1 infection
Prophylaxis
Mother-to-child transmission HIV-1
Thailand
Developing Countries
Lead sponsor: Institut de Recherche pour le Developpement
Sponsor class: OTHER_GOV
Collaborators: name: Harvard School of Public Health (HSPH)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2012-01-18
Enrollment: 379
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Rate of perinatal HIV transmission
timeFrame: 6 months
Secondary outcomes:
measure: Safety for women and neonates
timeFrame: Up to 12 Months
measure: Pregnancy outcomes
timeFrame: Up to 12 Months
Other outcomes:
Locations:
city: Chanthaburi
country: Thailand
facility: Prapokklao Hospital
state: Chantaburi
city: Chom Thong
country: Thailand
facility: Chomthong Hospital
state: Chiang Mai
city: Fang
country: Thailand
facility: Fang Hospital
state: Chiang Mai
city: Mae Rim
country: Thailand
facility: Nakornping Hospital
state: Chiang Mai
city: San Pa Tong
country: Thailand
facility: Sanpatong Hospital
state: Chiang Mai
city: Mae Chan
country: Thailand
facility: Mae Chan Hospital
state: Chiang Rai
city: Phan
country: Thailand
facility: Phan Hospital
state: Chiang Rai
city: Chiang Rai
country: Thailand
facility: Chiangrai Prachanukroh Hospital
state: Chiangrai
city: Chiang Rai
country: Thailand
facility: Wiangpapao Hospital
state: Chiangrai
city: Chiang Saen
country: Thailand
facility: Chiang Saen Hospital
state: Chiangrai
city: Bang Lamung
country: Thailand
facility: Banglamung Hospital
state: Chonburi
city: Chon Buri
country: Thailand
facility: Chonburi Hospital
state: Chonburi
city: Chon Buri
country: Thailand
facility: Panasnikom Hospital
state: Chonburi
city: Maha Sarakham
country: Thailand
facility: Mahasarakam Hospital
state: Mahasarakam
city: Nakhon Pathom
country: Thailand
facility: Nakhonpathom Hospital
state: Nakhonpathom
city: Chiang Kham
country: Thailand
facility: Chiang Kham Hospital
state: Phayao
city: Phitsanulok
country: Thailand
facility: Buddhachinaraj Hospital
state: Pitsanuloke
city: Samut Prakan
country: Thailand
facility: Samutprakarn Hospital
state: Samutprakarn
city: Samut Sakhon
country: Thailand
facility: Samutsakhon Hospital
state: Samutsakhon
city: Hat Yai
country: Thailand
facility: Hat Yai Hospital
state: Songkla
city: Bangkok
country: Thailand
facility: Bhumibol Adulyadej Hospital
city: Bangkok
country: Thailand
facility: Nopparat Rajathanee Hospital
city: Chachoengsao
country: Thailand
facility: Bhuddasothorn Hospital
city: Chiang Mai
country: Thailand
facility: Health Promotion Center Region 10, Chiang Mai
city: Kalasin
country: Thailand
facility: Kalasin Hospital
city: Khon Kaen
country: Thailand
facility: Khon Kaen Hospital
city: Khon Kaen
country: Thailand
facility: Regional Health Promotion Centre 6, Khon Kaen
city: Lampang
country: Thailand
facility: Lampang Hospital
city: Lamphun
country: Thailand
facility: Lamphun Hospital
city: Nakhon Si Thammarat
country: Thailand
facility: Maharaj Nakhon Si Thammarat Hospital
city: Nong Khai
country: Thailand
facility: Nong Khai Hospital
city: Nonthaburi
country: Thailand
facility: Pranangklao Hospital
city: Phayao
country: Thailand
facility: Phayao Provincial Hospital
city: Phuket
country: Thailand
facility: Vachira Phuket Hospital
city: Rayong
country: Thailand
facility: Rayong Hospital
city: Songkhla
country: Thailand
facility: Songkhla Hospital
Study officials:
affiliation: Institut de Recherche pour le Developpement
name: Marc Lallemant, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.