HIVS4NCT02249962
Option B+: Study on Safety, Viral Suppression, and Survival on Second Line ART
An observational study of HIV and Infant Exposure to Efavirenz, run by University of North Carolina, Chapel Hill at 1 site in Malawi.
Trial summary
To characterize safety, durability, antiretroviral treatment (ART) resistance, and clinical outcomes for mothers and infants exposed to the efavirenz-based Option B+ regimen for Prevention of Mother to Child Transmission (PMTCT) and HIV treatment in Malawi. Read more about this study
- Who is it for?
- Ages 16 to 50 years, women only
- Conditions the study is for
- HIV, Infant Exposure to Efavirenz
- How many people
- 12,011 participants
- Where
- 1 siteMalawi
- Study dates
- May 2015to Sep 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
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 16 to 50 years
- Women only
- No healthy volunteers
- Child, Adult
Study population: HIV+ pregnant women and their infants recruited from three clinic sites in Lilongwe, Malawi.
Who may be able to join
- Female age ≥16 (includes adults and emancipated minors)
- HIV positive by 2 rapid tests approved by the Malawi Ministry of Health
- Willingness to provide informed consent
Who cannot join
- Female <16 years
- HIV negative
- Incapable of providing informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Option B+: ART Safety and Durability During First and Subsequent Pregnancies
To characterize safety, durability, antiretroviral treatment (ART) resistance, and clinical outcomes for mothers and infants exposed to the efavirenz-based Option B+ regimen for Prevention of Mother to Child Transmission (PMTCT) and HIV treatment in Malawi.
Read the detailed description
Option B+ is an innovative strategy pioneered within Malawi that provides universal lifelong ART (tenofovir/lamivudine/efavirenz: TDF/3TC/EFV) for pregnant and breastfeeding women to promote maternal health and prevent HIV transmission to infants. The safety of a TDF/3TC/EFV based regimen used during pregnancy has not been systematically evaluated.
Objective 1: To characterize the long term safety, drug resistance patterns and clinical outcomes among women and their infants enrolled in the Malawi Option B+ program using TDF/3TC/EFV.
- Hypothesis 1: Over 3+ years of anticipated treatment follow-up, TDF/3TC/EFV will be associated with a toxicity rate requiring ART discontinuation of <3% and >90% virologic suppression at 36 months.
- Hypothesis 2: Women with baseline CD4 counts ≤ 350 cells/mm3 will experience greater rates of clinical events, treatment failure and ART toxicity compared to those with CD4 > 350 cells/mm3.
Objective 2: To critically evaluate women with subsequent pregnancies after initial engagement in the Option B+ Program.
Objective 2a: To determine the prevalence of treatment failure among pregnant women presenting to ANC on first-line therapy and evaluate the safety of ATZ/r based therapy among those women requiring second-line therapy.
- Hypothesis 1: HIVRNA testing at first ANC visit among women with subsequent pregnancies will demonstrate that approximately 5% of women will be failing treatment and will identify key risk factors associated with treatment failure.
- Hypothesis 2: ATZ/r based therapy during pregnancy is associated with toxicity rates requiring discontinuation in less than 5% of pregnant women.
Objective 2b: Among pregnant women defaulting from TDF/3TC/EFV, determine the treatment response to re-initiation of first-line therapy, need for second-line therapy, and characterize resistance.
- Hypothesis 1: Women re-engaging in care after program default will experience early ART treatment failure due to HIV drug resistance that developed after ART cessation during initial care.
Objective 3: To explore rates of adverse pregnancy and birth outcomes among women, presence of birth defects, and infant developmental delay among infants exposed to EFV-based ART after the first trimester (Objective 1), Efavirenz at conception (Objective 2a), and on second-line therapy with ATZ/r based ART (Objective 2a).
- Hypothesis 1: Efavirenz exposure during the first trimester is associated with a higher rate of adverse pregnancy and birth outcomes than if exposed later in pregnancy.
- Hypothesis 2: Infants exposed to EFV from first trimester will experience lower mean scores on Bayley neurodevelopment domains than those exposed later in pregnancy.
The investigators will collect data for maternal treatment outcomes, including vital status, per the national HIV program definitions: Alive, Dead, Default (>3 months since last visit), Stop, and Transfer Out. In addition to maternal treatment outcomes, the national HIV program collects data regarding the following outcomes, which the investigators will also collect: pregnancy and tuberculosis incidence after ART initiation, drug toxicity/ adverse event (Rash, Hepatitis, Lactic Acidosis, Anemia, Peripheral Neuropathy), adherence measurement (by pill count), WHO clinical stage at ART initiation, ART pharmacy refill information, and ART regimen.
- Conditions
- HIV, Infant Exposure to Efavirenz
- Keywords
- prospective, cohort
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Overall cohort: HIV+ women on Option B+ and their infants | Women (n=8000) visiting an antenatal clinic for care who will be followed prospectively for Malawi standard treatment outcomes and pregnancy outcomes as patients on Option B+ | |
| Sub-cohort A: first HIV diagnosis | Women (n=300) who present to the antenatal care clinic and are diagnosed for the first time with HIV. These women will be started on Option B+ as anti-retroviral treatment, per Malawi Ministry of Health standard of care. | |
| Sub-cohort B: subsequent pregnancies failing 1st line ART | Women (n=150) who have failed first-line treatment (TDF/3TC/EFV) based on HIV RNA levels and CD4 count. These women will be switched to second-line treatment (AZT/3TC/ATZ/r) per Malawi Ministry of Health standard of care. | |
| Sub-cohort C: subsequent pregnancies who default from 1st line | Women (n=150) who are HIV+ and have a subsequent pregnancy who have not been adherent to first-line (Option B+: TDF/3TC/EFV). These women will be re-initiated on first-line treatment for 3 months, then evaluated to assess whether continuation on first-line treatment is sufficient, or if they need to be switched to second-line treatment (AZT/3TC/ATZ/r) per Malawi Ministry of Health standard of care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with failure on Option B+ first-line treatment
Proportion of women who fail first-line treatment as indicated by one or more of the following criteria: WHO Stage 3 or 4 events (as defined by Appendix 60 of the Adult AIDS Clinical Trials Group (AACTG)), or DAIDS grade 3 or 4 toxicity (lab serum markers), or proportion with treatment discontinuation (or death), or proportion with virologic failure (as measured by HIV RNA levels)
Measured: Up to 36 months
Secondary outcomes (11)
Pharmacokinetic: progesterone level in women using contraceptive implant
Measure of serum progesterone and efavirenz levels among women with a contraceptive implant
Measured: months 3, 6, 12, 24
Micronutrient assessment
Measured: Baseline, months 6, 12, 24, 36
Maternal CD4 count
Standard of care
Measured: baseline, months 12, 24, 36 post-ART initiation
HIV RNA level measurement
Standard of Care, measured to assess resistance to first-line ART
Measured: baseline, months 3, 6, 12, 24, 36
PHQ-9 evaluation
Assess maternal psychological well-being
Measured: baseline, months 6, 12, 18, 24, 30, 36
Laboratory serum markers
Labs assessed include: renal function (creatinine and urinalysis), liver function, and hematology Measurements contribute to DAIDS grade 3 or 4 toxicity assessment.
Measured: baseline, months 3, 6, 9, 12, 18, 24, 30, 36
Pregnancy outcome assessment
Status of birth (live, stillborn, miscarriage), small for gestational age, congenital anomalies
Measured: At time of pregnancy completion (birth, termination)
HIV antibody testing- infant
Measured: age 1 year
Infant neuro-development assessment: Bayley score
Measured: Age 3 weeks, months 3, 6, 12, 18, 24, 30, 36
Family planning use and proportion of women with subsequent pregnancy by 36 months
Assessing women's fertility preferences, usage of family planning methods, and pregnancy status post-ART initiation
Measured: Up to 36 months
ART Adherence: pill-count
Assessment of adherence to anti-retroviral medications via direct pill count at each clinic visit
Measured: months 3, 6, 9, 12, 18, 24, 30, 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2014 (estimated)
- Study startMay 2015
- Primary completionSep 2020
- Study completionSep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 12,011 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Malawi, University of North Carolina, Lighthouse Trust, Baylor College of Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Mina C Hosseinipour, MD, MPH, Principal investigator, UNC Project- Malawi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02249962
- Sponsor's protocol ID
- 14-1633
- Other IDs
- R01HD080485
- Acronym
- S4
- Status last verified
- May 2020
- First submitted
- 11 Sep 2014
- Last updated
- 12 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Option B+: ART Safety and Durability During First and Subsequent Pregnancies
- ClinicalTrials.gov ID
- NCT02249962
- Acronym / sponsor ID
- S4 / 14-1633
- Conditions
- HIV, Infant Exposure to Efavirenz
- Keywords
- prospective, cohort
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 12,011 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Ministry of Health, Malawi, University of North Carolina, Lighthouse Trust, Baylor College of Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- May 2015 (actual)
- Primary completion
- Sep 2020 (actual)
- Study completion
- Sep 2020 (actual)
- First posted
- 26 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To characterize safety, durability, antiretroviral treatment (ART) resistance, and clinical outcomes for mothers and infants exposed to the efavirenz-based Option B+ regimen for Prevention of Mother to Child Transmission (PMTCT) and HIV treatment in Malawi.
Detailed description
Option B+ is an innovative strategy pioneered within Malawi that provides universal lifelong ART (tenofovir/lamivudine/efavirenz: TDF/3TC/EFV) for pregnant and breastfeeding women to promote maternal health and prevent HIV transmission to infants. The safety of a TDF/3TC/EFV based regimen used during pregnancy has not been systematically evaluated.
Objective 1: To characterize the long term safety, drug resistance patterns and clinical outcomes among women and their infants enrolled in the Malawi Option B+ program using TDF/3TC/EFV.
- Hypothesis 1: Over 3+ years of anticipated treatment follow-up, TDF/3TC/EFV will be associated with a toxicity rate requiring ART discontinuation of <3% and >90% virologic suppression at 36 months.
- Hypothesis 2: Women with baseline CD4 counts ≤ 350 cells/mm3 will experience greater rates of clinical events, treatment failure and ART toxicity compared to those with CD4 > 350 cells/mm3.
Objective 2: To critically evaluate women with subsequent pregnancies after initial engagement in the Option B+ Program.
Objective 2a: To determine the prevalence of treatment failure among pregnant women presenting to ANC on first-line therapy and evaluate the safety of ATZ/r based therapy among those women requiring second-line therapy.
- Hypothesis 1: HIVRNA testing at first ANC visit among women with subsequent pregnancies will demonstrate that approximately 5% of women will be failing treatment and will identify key risk factors associated with treatment failure.
- Hypothesis 2: ATZ/r based therapy during pregnancy is associated with toxicity rates requiring discontinuation in less than 5% of pregnant women.
Objective 2b: Among pregnant women defaulting from TDF/3TC/EFV, determine the treatment response to re-initiation of first-line therapy, need for second-line therapy, and characterize resistance.
- Hypothesis 1: Women re-engaging in care after program default will experience early ART treatment failure due to HIV drug resistance that developed after ART cessation during initial care.
Objective 3: To explore rates of adverse pregnancy and birth outcomes among women, presence of birth defects, and infant developmental delay among infants exposed to EFV-based ART after the first trimester (Objective 1), Efavirenz at conception (Objective 2a), and on second-line therapy with ATZ/r based ART (Objective 2a).
- Hypothesis 1: Efavirenz exposure during the first trimester is associated with a higher rate of adverse pregnancy and birth outcomes than if exposed later in pregnancy.
- Hypothesis 2: Infants exposed to EFV from first trimester will experience lower mean scores on Bayley neurodevelopment domains than those exposed later in pregnancy.
The investigators will collect data for maternal treatment outcomes, including vital status, per the national HIV program definitions: Alive, Dead, Default (>3 months since last visit), Stop, and Transfer Out. In addition to maternal treatment outcomes, the national HIV program collects data regarding the following outcomes, which the investigators will also collect: pregnancy and tuberculosis incidence after ART initiation, drug toxicity/ adverse event (Rash, Hepatitis, Lactic Acidosis, Anemia, Peripheral Neuropathy), adherence measurement (by pill count), WHO clinical stage at ART initiation, ART pharmacy refill information, and ART regimen.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Overall cohort: HIV+ women on Option B+ and their infants | – | –Women (n=8000) visiting an antenatal clinic for care who will be followed prospectively for Malawi standard treatment outcomes and pregnancy outcomes as patients on Option B+ |
| Sub-cohort A: first HIV diagnosis | – | –Women (n=300) who present to the antenatal care clinic and are diagnosed for the first time with HIV. These women will be started on Option B+ as anti-retroviral treatment, per Malawi Ministry of Health standard of care. |
| Sub-cohort B: subsequent pregnancies failing 1st line ART | – | –Women (n=150) who have failed first-line treatment (TDF/3TC/EFV) based on HIV RNA levels and CD4 count. These women will be switched to second-line treatment (AZT/3TC/ATZ/r) per Malawi Ministry of Health standard of care. |
| Sub-cohort C: subsequent pregnancies who default from 1st line | – | –Women (n=150) who are HIV+ and have a subsequent pregnancy who have not been adherent to first-line (Option B+: TDF/3TC/EFV). These women will be re-initiated on first-line treatment for 3 months, then evaluated to assess whether continuation on first-line treatment is sufficient, or if they need to be switched to second-line treatment (AZT/3TC/ATZ/r) per Malawi Ministry of Health standard of care. |
Who may qualify
- Ages
- 16 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- HIV+ pregnant women and their infants recruited from three clinic sites in Lilongwe, Malawi.
Key inclusion criteria (3 listed)
- Female age ≥16 (includes adults and emancipated minors)
- HIV positive by 2 rapid tests approved by the Malawi Ministry of Health
- Willingness to provide informed consent
Key exclusion criteria (3 listed)
- Female <16 years
- HIV negative
- Incapable of providing informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Proportion of participants with failure on Option B+ first-line treatment
Time frame: Up to 36 months
Proportion of women who fail first-line treatment as indicated by one or more of the following criteria: WHO Stage 3 or 4 events (as defined by Appendix 60 of the Adult AIDS Clinical Trials Group (AACTG)), or DAIDS grade 3 or 4 toxicity (lab serum markers), or proportion with treatment discontinuation (or death), or proportion with virologic failure (as measured by HIV RNA levels)
11 secondary outcomes
Pharmacokinetic: progesterone level in women using contraceptive implant
Time frame: months 3, 6, 12, 24
Micronutrient assessment
Time frame: Baseline, months 6, 12, 24, 36
Maternal CD4 count
Time frame: baseline, months 12, 24, 36 post-ART initiation
HIV RNA level measurement
Time frame: baseline, months 3, 6, 12, 24, 36
PHQ-9 evaluation
Time frame: baseline, months 6, 12, 18, 24, 30, 36
Laboratory serum markers
Time frame: baseline, months 3, 6, 9, 12, 18, 24, 30, 36
Pregnancy outcome assessment
Time frame: At time of pregnancy completion (birth, termination)
HIV antibody testing- infant
Time frame: age 1 year
Infant neuro-development assessment: Bayley score
Time frame: Age 3 weeks, months 3, 6, 12, 18, 24, 30, 36
Family planning use and proportion of women with subsequent pregnancy by 36 months
Time frame: Up to 36 months
ART Adherence: pill-count
Time frame: months 3, 6, 9, 12, 18, 24, 30, 36
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mina C Hosseinipour, MD, MPH principal investigator
UNC Project- Malawi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV and Infant Exposure to Efavirenz, run by University of North Carolina, Chapel Hill at 1 site in Malawi.
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 3 inclusion and 3 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 12 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malawi. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proportion of participants with failure on Option B+ first-line treatment (time frame: Up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Mar 2021.