Comparison of Three Anti-HIV Regimens to Prevent Nevirapine Resistance in Women Who Take Nevirapine During Pregnancy

HIV Infections Clinical Trial

Official title:

Maintaining Options for Mothers Study (MOMS): A Phase II Randomized Comparison of Three Antiretroviral Strategies Administered for 7 or 21 Days to Reduce the Emergence of Nevirapine Resistant HIV-1 Following a Single Intrapartum Dose of Nevirapine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00099632
• Other study ID #: A5207
• Secondary ID: 10127ACTG A5207M
• Status: Completed
• Phase: Phase 2
• Start date: March 2006
• Est. completion date: November 2011

Study information

• Verified date: January 2019
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

HIV infected pregnant women may take single-dose nevirapine (SD NVP) prior to giving birth to prevent mother-to-child transmission (MTCT) of HIV. However, SD NVP may cause NVP resistance in the mother, potentially ruling out some treatment options in the future. The purpose of this study is to determine which of three anti-HIV drug regimens most effectively reduces the development of maternal NVP resistance in HIV infected pregnant women. The effectiveness of short-term (7 day therapy) versus long-term (21-day therapy) regimens will also be compared.

The study hypotheses are: 1) intrapartum SD NVP with a 21-day course of antiretroviral therapy (ART) results in less frequent selection of NVP-resistant HIV-1 variants than intrapartum SD NVP with a 7-day course of ART, and 2) a 7- or 21-day course of lamivudine/zidovudine (3TC/ZDV), emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), or lopinavir/ritonavir (LPV/r) following SD NVP will not select nucleoside reverse transcriptase inhibitor (NRTI)- or protease inhibitor (PI)- resistant HIV-1 variants.

Description:

A major disadvantage of giving SD NVP is the potential for maternal development of NVP resistance and additional resistance to other nonnucleoside reverse transcriptase inhibitors (NNRTI) in the mother; as a result, future treatment options may be limited for these HIV infected women. The purpose of the study is to determine which of three ART regimens most effectively deters the development of maternal NVP resistance in HIV infected pregnant women postpartum. This study also compared the effectiveness of short-term versus long-term ART in discouraging the development of maternal NVP resistance.

Some mothers in this study received ZDV monotherapy prior to SD NVP administration; initiation of ZDV monotherapy was at the discretion of the site investigator and was be provided by this study. Randomization was stratified by receipt of ZDV monotherapy during the pregnancy.

Prior to labor, mothers were randomly assigned to receive SD NVP at the onset of labor and one of three postpartum ART regimens: 3TC/ZDV, FTC/TDF, and LPV/r. In addition, participants were randomly assigned to receive 7 or 21 days of their assigned postpartum treatment.

Mothers were followed for 96 weeks following delivery; there were 11 study visits for mothers during the study. At the onset of labor, medical and medication history, a targeted physical exam, and an obstetrical exam occurred. Additional physical exams occurred on Day 1 and Weeks 1 and 3. Blood collection occurred at 8 study visits between Weeks 3 and 96. Infants were followed for up to 96 weeks after birth; there were 8 study visits for infants during the study. Infants who had ever been breastfed had study visits at Weeks 16, 24, 48, and 96, and at about 1 and 2 years of age. A physical exam, medication history, and blood collection occurred at each infant visit. Mothers and infants could be prescribed continuing ART, but such ART was be provided by this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 484
• Est. completion date: November 2011
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 13 Years and older

Eligibility

Inclusion Criteria for Mothers:

• HIV-1 infected

• CD4 count 250 cells/mm3 or greater within 30 days of study entry

• The following laboratory values obtained within 30 days prior to study entry: absolute neutropil count >= 750/mm3; hemoglobin >= 8.0 g/dL; platelet count >= 50,000/mm3; calculated creatinine clearance (Cockcroft-Gault formula) > 60 mL/min; AST(SGOT) and ALT(SGPT) < 5 x ULN; total bilirubin < 1.5 X ULN.

• Pregnant with a viable fetus at 28 to 38 weeks gestation at study entry.

• Willing to give birth to baby in a hospital or clinic

• Written informed consent from parent or guardian, if applicable

Exclusion Criteria for Mothers:

• Any ART, including single-dose NVP, prior to study entry. Mothers who receive ZDV monotherapy prior to labor under the supervision of the site investigator are not excluded.

• Known allergy or sensitivity to study drugs or their formulations

• Current drug or alcohol abuse that may interfere with the study

• Serious illness requiring systemic treatment or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded.

• Hepatitis B surface antigen positive within 180 days prior to study entry

• Active tuberculosis infection requiring treatment

• Prior enrollment in this study

• Expect to use ART, except ZDV monotherapy, prior to onset of labor

• Expect to use ART other than study medications from delivery to 9 weeks postpartum

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Emtricitabine/Tenofovir Disoproxil Fumarate
200mg/300mg as one tablet taken orally once daily
• Lamivudine/Zidovudine
150mg/300mg as one tablet taken orally twice daily
• Lopinavir/Ritonavir
133.3mg/33.3mg as three capsules taken orally twice daily
• single dose Nevirapine
one 200 mg tablet taken orally

Locations

Country	Name	City	State
Haiti	Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS	Port-au-Prince
India	Chennai Antiviral Research and Treatment (CART) CRS	Chennai	Tamil Nadu
India	Byramjee Jeejeebhoy Government Medical College CRS	Pune	Maharashtra
Malawi	Blantyre CRS	Blantyre
South Africa	Wits Helen Joseph Hospital CRS (Wits HJH CRS)	Johannesburg	Gauteng
South Africa	Durban International CRS	Westville	KwaZulu-Natal
Tanzania	Kilimanjaro Christian Medical CRS	Moshi
Uganda	Joint Clinical Research Center (JCRC)/Kampala CRS	Kampala

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

Haiti,  India,  Malawi,  South Africa,  Tanzania,  Uganda, 

References & Publications (7)

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. Epub 2002 Jun 26. — View Citation

Eshleman SH, Jackson JB. Nevirapine resistance after single dose prophylaxis. AIDS Rev. 2002 Apr-Jun;4(2):59-63. Review. — View Citation

Hong F, Halvas E, Chan E, Zheng L, Hughes M, Hitti J, McMahon D, Mellors J. Suppression of Minor NVP-Resistant Variants With 7- vs. 21-Day Antiretroviral Regimens After Single Dose Nevirapine. Presented at 20th Anniversary of the International Workshop on

Jourdain G, Ngo-Giang-Huong N, Le Coeur S, Bowonwatanuwong C, Kantipong P, Leechanachai P, Ariyadej S, Leenasirimakul P, Hammer S, Lallemant M; Perinatal HIV Prevention Trial Group. Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N Engl J Med. 2004 Jul 15;351(3):229-40. Epub 2004 Jul 9. — View Citation

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. Erratum in: AIDS. 2007 Jul 31;21(12):1671. — View Citation

McMahon D, Noel F, Zheng L, Kabanda J, Halvas E, Taulo F, Kumarasamy N, Wallis C, Hughes M, Mellors J. Suppression of NVP Resistance with 7- vs 21-day ARV Regimens after Single-dose NVP: Results of A5207. Presented at 18th Conference on Retroviruses & Opp

Sullivan JL. Prevention of mother-to-child transmission of HIV--what next? J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S67-72. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping	For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed to the primary endpoint; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed to primary endpoint.; 10 participants who did not have resistance samples available were excluded from the primary endpoint analysis.	2 and 6 weeks after completion of treatment
Secondary	Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping.	For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed.	2 and 6 weeks after completion of treatment
Secondary	Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping.	For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed.	2 and 6 weeks after completion of treatment
Secondary	Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12	Grade 3 or higher signs and symptoms, laboratory abnormalities, events that are reported through the EAE system, and any grade event that leads to a treatment change from first day of study treatment to week 12.; Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death	From first day of study treatment to week 12
Secondary	Number of Participants Who Discontinued Study Treatment Prematurely	participants assigned to 7-day treatment arm and 21-day treatment arm were supposed to stay in study treatment for 7 days and 21 days respectively.	From first day of study treatment to last day of study treatment (up to 21 days)

External Links

•   Click here for more information on HIV and pregnancy
•   Click here for more information on medication regimens for HIV positive pregnant women
•   Haga clic aquí para más información acerca de los tratamientos para las mujeres embarazadas infectadas por el VIH
•   Haga clic aquí para más información acerca del VIH y el embarazo
•   Haga clic aquí para ver información sobre este ensayo clínico en español.