HIV InfectionsPhase 2NCT00099632
Comparison of Three Anti-HIV Regimens to Prevent Nevirapine Resistance in Women Who Take Nevirapine During Pregnancy
A Phase 2 study testing Emtricitabine/Tenofovir Disoproxil Fumarate, Lamivudine/Zidovudine and Lopinavir/Ritonavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 8 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages 13 years and older, women only
- Conditions the study is for
- HIV Infections
- What is being tested?
- Emtricitabine/Tenofovir Disoproxil Fumarate, Lamivudine/Zidovudine and Lopinavir/Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 484 participants
- Where
- 8 sitesin 6 countries
- Study dates
- Mar 2006to Nov 2011
- Phase
- Phase 2
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 13 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
8 sites in 6 countries.
8 sites in 6 countries
India2 sites
Chennai Antiviral Research and Treatment (CART) CRS
Chennai, Tamil Nadu, 600113
Byramjee Jeejeebhoy Government Medical College CRS
Pune, Maharashtra, 411001
South Africa2 sites
Wits Helen Joseph Hospital CRS (Wits HJH CRS)
Johannesburg, Gauteng, 2092
Durban International CRS
Westville, KwaZulu-Natal, 3610
Haiti1 site
Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
Port-au-Prince, 6110
About this study
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
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.
Read the detailed 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.
- Conditions
- HIV Infections
- Being tested
- Emtricitabine/Tenofovir Disoproxil Fumarate, Lamivudine/Zidovudine, Lopinavir/Ritonavir, single dose Nevirapine
- Keywords
- Treatment Naive
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emtricitabine/Tenofovir Disoproxil FumarateDrug
Also called FTC/TDF
200mg/300mg as one tablet taken orally once daily
Lamivudine/ZidovudineDrug
Also called 3TC/ZDV
150mg/300mg as one tablet taken orally twice daily
Lopinavir/RitonavirDrug
Also called LPV/r
133.3mg/33.3mg as three capsules taken orally twice daily
single dose NevirapineDrug
Also called SD NVP
one 200 mg tablet taken orally
| Study group | Role | What they receive |
|---|---|---|
| 7-day 3TC/ZDV | Experimental | SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV. Receives: Drug: Lamivudine/Zidovudine; Drug: single dose Nevirapine |
| 21-day 3TC/ZDV | Experimental | SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV. Receives: Drug: Lamivudine/Zidovudine; Drug: single dose Nevirapine |
| 7-day FTC/TDF | Experimental | SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF. Receives: Drug: Emtricitabine/Tenofovir Disoproxil Fumarate; Drug: single dose Nevirapine |
| 21-day FTC/TDF | Experimental | SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF. Receives: Drug: Emtricitabine/Tenofovir Disoproxil Fumarate; Drug: single dose Nevirapine |
| 7-day LPV/r | Experimental | SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r. Receives: Drug: Lopinavir/Ritonavir; Drug: single dose Nevirapine |
| 21-day LPV/r | Experimental | SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r Receives: Drug: Lopinavir/Ritonavir; Drug: single dose Nevirapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 and 6 weeks after completion of treatment
Secondary outcomes (4)
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.
Measured: 2 and 6 weeks after completion of treatment
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.
Measured: 2 and 6 weeks after completion of treatment
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
Measured: From first day of study treatment to week 12
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.
Measured: From first day of study treatment to last day of study treatment (up to 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2004 (estimated)
- Study startMar 2006
- Primary completionApr 2010
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 484 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jane Hitti, MD, MPH, Study chair, Department of Obstetrics/Gynecology, Perinatal Medicine, University of Washington Medical CenterDeborah McMahon, MD, Study chair, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00099632
- Sponsor's protocol ID
- A5207
- Other IDs
- 10127, ACTG A5207, MOMS
- Status last verified
- Jan 2019
- First submitted
- 17 Dec 2004
- Last updated
- 4 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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 12134253Eshleman SH, Jackson JB. Nevirapine resistance after single dose prophylaxis. AIDS Rev. 2002 Apr-Jun;4(2):59-63.
PubMed 12152519Jourdain 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. doi: 10.1056/NEJMoa041305. Epub 2004 Jul 9.
PubMed 15247339Lyons 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 15627034Sullivan 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 14562860McMahon 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 & Opportunistic Infections (CROI 11) on 03/01/2011 at Boston, MA
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 HIV & Hepatitis Virus Drug Resistance and Curative Strategies on Jun 9, 2011, Los Cabos, Mexico
McMahon DK, Zheng L, Hitti J, Chan ES, Halvas EK, Hong F, Kabanda J, Taulo F, Kumarasamy N, Bonhomme J, Wallis CL, Klingman KL, Hughes MD, Mellors JW. Greater suppression of nevirapine resistance with 21- vs 7-day antiretroviral regimens after intrapartum single-dose nevirapine for prevention of mother-to-child transmission of HIV. Clin Infect Dis. 2013 Apr;56(7):1044-51. doi: 10.1093/cid/cis1219. Epub 2013 Jan 8.
PubMed 23300238