Option B+: Study on Safety, Viral Suppression, and Survival on Second Line ART

HIV Clinical Trial

— S4  

Official title:

Option B+: ART Safety and Durability During First and Subsequent Pregnancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02249962
• Other study ID #: 14-1633
• Secondary ID: R01HD080485
• Status: Completed
• Start date: May 2015
• Est. completion date: September 2020

Study information

• Verified date: May 2020
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12011
• Est. completion date: September 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Female <16 years

• HIV negative

• Incapable of providing informed consent

Related Conditions & MeSH terms

• HIV
• Infant Exposure to Efavirenz

Locations

Country	Name	City	State
Malawi	UNC Project Malawi	Lilongwe

Sponsors (6)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Baylor College of Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Lighthouse Trust, Ministry of Health and Population, Malawi, University of North Carolina

Country where clinical trial is conducted

Malawi, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Up to 36 months
Secondary	Pharmacokinetic: progesterone level in women using contraceptive implant	Measure of serum progesterone and efavirenz levels among women with a contraceptive implant	months 3, 6, 12, 24
Secondary	Micronutrient assessment		Baseline, months 6, 12, 24, 36
Secondary	Maternal CD4 count	Standard of care	baseline, months 12, 24, 36 post-ART initiation
Secondary	HIV RNA level measurement	Standard of Care, measured to assess resistance to first-line ART	baseline, months 3, 6, 12, 24, 36
Secondary	PHQ-9 evaluation	Assess maternal psychological well-being	baseline, months 6, 12, 18, 24, 30, 36
Secondary	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.	baseline, months 3, 6, 9, 12, 18, 24, 30, 36
Secondary	Pregnancy outcome assessment	Status of birth (live, stillborn, miscarriage), small for gestational age, congenital anomalies	At time of pregnancy completion (birth, termination)
Secondary	HIV antibody testing- infant		age 1 year
Secondary	Infant neuro-development assessment: Bayley score		Age 3 weeks, months 3, 6, 12, 18, 24, 30, 36
Secondary	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	Up to 36 months
Secondary	ART Adherence: pill-count	Assessment of adherence to anti-retroviral medications via direct pill count at each clinic visit	months 3, 6, 9, 12, 18, 24, 30, 36