Study Details

Protocol Status: Withdrawn
Study Purpose:

To determine whether a strategy of combined nevirapine access (where pregnant women who are identified as HIV-infected as well as women who choose not to be tested) will result in superior NVP coverage to that achieved by a strategy of targeted NVP access (where only pregnant women identified as HIV-infected are provided NVP).

Study Design:

This study will be comprised of two interrelated components that will proceed concurrently:
A population-based general surveillance component ("general surveillance component"), in which unlinked, anonymous cord blood specimens will be obtained from the discarded placentas of all women delivering at public delivery centers in Lusaka, Zambia during a specified period and tested for HIV and the presence of NVP.
A two-arm cluster-randomized trial component, in which participating clinics will be randomly assigned to provide either targeted or combined access to NVP in a 1:1 allocation.

Study Population:

Because of the population-based nature of the protocol, the various study outcomes will be measured in three different populations:
HIV testing uptake population: all women who initiate antenatal care after randomization at a participating study clinic
054 surveillance population: all women who deliver at a participating study clinic during the delivery period except those who initiated antenatal care prior to randomization; this is the population in which the primary outcome of maternal NVP coverage will be measured
safety and attitudes cohort: a subset of the 054 surveillance population, this cohort includes women who provide informed consent to complete a questionnaire on factors influencing the decision to be tested for HIV and to take NVP, particularly social harms, as well as provide permission to assess safety and toxicity endpoints (life threatening illness and death of either mother or infant). Toxicity data will be collected through time of discharge following delivery.

Study Size:

20 clinical sites, each enrolling at least 154 women over a period of three months, of whom 25% are anticipated to be HIV-infected.

Study Duration:

The entire study will be conducted over the course of approximately 7 months.

Prevention of mother-to-child transmission (PMTCT) services are already offered according to the targeted NVP strategy in all public antenatal clinics in Lusaka. Following randomization (in which half of the participating L&D clinics will be assigned to the combined access arm and half of the participating antenatal clinics will be assigned to the combined arm) there will be a 4-month run-in period to allow all women delivering at participating facilities to have been exposed to the antenatal intervention. After the run-in period, a 3-month delivery period will ensue during which the surveillance component will be conducted to assess NVP coverage in HIV-infected women. Data on social harm, and choices and opinions about HIV testing and NVP uptake as well as toxicity data will be collected form those participants who agree to be part of the safety and attitudes cohort.

Treatment Regimen:

Clinics in both randomization arms will provide individual pretest counseling to all women and offer voluntary HIV testing as per standard of care. Clinics randomized to the targeted strategy will offer NVP only to those women who are already known to be or are found to be HIV infected through voluntary testing (also per the current standard of care in Lusaka). Clinics randomized to the combined strategy will offer NVP to those women identified as HIV infected through voluntary testing, to those who decline testing after individual pretest counseling and to those who present for delivery without having been offered NVP previously.

Primary Objectives:

To compare the rate of maternal NVP coverage, defined as the proportion of HIV-infected women in the 054 surveillance population who have NVP detected in their cord blood at delivery, achieved by a strategy of combined access to that achieved by a strategy of targeted access in a high prevalence setting in sub-Saharan Africa.

Secondary Objectives:

HIV testing population:
To measure testing uptake, defined as the proportion of women in the HIV testing uptake population who undergo VCT and receive their HIV test results

054 surveillance population:
To estimate maternal NVP coverage in HIV-infected women according to intervention arm and antenatal testing status
To determine timing of NVP ingestion (self-dosed prior to arrival to study clinic or upon arrival to study clinic) in HIV-infected women according to intervention arm and antenatal testing status
To determine infant NVP coverage, defined as the proportion of infants born to HIV-infected mothers who are directly observed being administered NVP syrup
To measure NVP exposure in a sample of HIV-negative women in the combined arm

Safety and attitudes cohort:
To assess significant NVP-attributable toxicity, defined as a life-threatening event or death in mothers or infants that are deemed by study physicians to be possibly, probably, or definitely attributable to single dose NVP
To collect self-reported cases of domestic violence/social ostracism
To compare attitudes and preferences of individuals toward the two NVP administration strategies

Study Sites List