Operational effectiveness of single-dose nevirapine in preventing mother-to-child transmission of HIV

Bulletin of the World Health Organization, Volume 85, No. 6, Year 2007

Interpretation

Objective: To determine the operational effectiveness of the South African programme for preventing mother-to-child transmission (PMTCT) of HIV in reducing rates of early transmission of infection. Methods: Participants were mother-infant pairs who participated in the South African PMTCT programme between October 2002 and November 2004. This was a prospective cohort study. Three sites in different provinces were selected to represent differences in socioeconomic status and HIV prevalence. Data on antenatal care and labour ward care were obtained from maternal interviews and from reviews of medical records. A total of 665 mother-infant pairs in which the mother was HIV-positive were recruited and 588 (88.4%) were followed up at 3 or 4 weeks postpartum to determine the HIV status and vital status of the infant. Findings: Rural participants were significantly poorer and their health care was significantly worse. Women of higher socioeconomic status and those who received better counselling were more likely to be treated with nevirapine. Rates of early HIV transmission ranged from 8.6% to 13.7%. Maternal viral load was the only statistically significant risk factor for transmission. After adjusting for maternal viral load and prevalence of low birth weight, the odds of transmission were 1.8 times higher at the rural site. Controlling for having had ≥ 4 antenatal visits and any delivery complication reduced the odds of transmission to 1.5 higher at the rural site. Conclusion: Rates of early transmission of HIV in an operational setting using single-dose nevirapine administered both to mother and child are similar to those obtained in clinical trials. Scaling up access to antiretroviral regimens for women will further reduce transmission to infants. This was a prospective cohort study of mothers and infants seen at three of the 18 national prevention programme pilot sites in South Africa between October 2002 and November 2004. Women were recruited at the health facility either before delivery or within a few days after delivery; they were visited again at 3 to 4 weeks post-delivery. Three areas (the main towns of Paarl and Rietvlei and the dormitory township of Umlazi) were selected to reflect different socioeconomic regions, rural and urban locations and antenatal prevalence rates of HIV. Paarl, in the Western Cape province, is a relatively well-resourced periurban and rural area with a well-functioning health system and a 2004 antenatal HIV prevalence of 9%.12 Rietvlei, a rural area in the Eastern Cape province, is in one of the poorest parts of South Africa and its antenatal HIV prevalence in 2004 was 28%.12 Umlazi, near the port of Durban in KwaZulu–Natal, is a periurban area with formal and informal housing. The socioeconomic status of residents is similar to that in Paarl but the health systems are weaker and the antenatal HIV prevalence in 2004 was 47%.12 All data were collected by trained field researchers. Mothers were interviewed using semistructured interviews at the time of recruitment and during the follow-up visit at 3 to 4 weeks. Topics covered included the extent of antenatal care received, plans for disclosure of HIV status and basic knowledge of HIV/AIDS and of mother-to-child transmission. Obstetric records were reviewed using a record review capture sheet to obtain data on antenatal and intrapartum risk factors for transmission. All interviews were conducted in the preferred language of the participant (Afrikaans, English, Xhosa or Zulu). Nevirapine was considered to have been taken by the mother according to protocol if it was taken between 2 and 24 hours before delivery; nevirapine was considered to have been administered to infants according to protocol if it was given within 72 hours after birth. A measure of socioeconomic status was devised using principal component factor analysis that included six household assets (presence of refrigerator, radio, television, stove, telephone or mobile phone, car) and a question regarding food security. This produced a weighted average, so items with a greater variability (e.g. television) contribute more to the score than items with a lesser variability (e.g. radio). The counselling index measured whether the following three topics were mentioned by the counsellor, nurse or midwife during the woman’s pregnancy (as recalled by the woman): the risk of mother-to-child transmission and breastfeeding, how women could choose the best method to feed their infant, and whether the advantages and disadvantages of feeding options were discussed and the woman was helped to make a suitable choice. For each topic a score of 1 was allocated if the topic was covered. If a mother recalled that she was simply told to formula-feed or to breastfeed, then the general counselling index for that mother was decreased by 1 point. Thus, scores on the counselling index ranged from –1 to 3. During the home visit at 3 to 4 weeks post-delivery, trained field staff collected blood spots on Guthrie cards from all infants and mothers by means of a heel or finger prick. Following overnight drying, the filter paper was inserted into a self-sealing envelope with desiccant. Blood specimens were couriered to the laboratory for analysis. HIV infection in infants was determined from dried blood spots using an HIV-1 RNA quantitation assay (nucleic acid sequence-based amplification with electro chemiluminescent detection, NucliSens HIV-1 QT) with a lower detection limit of 80 copies of HIV RNA per ml of blood (equivalent to 1600 copies HIV RNA per 50 μL dried blood spot)13 and a qualitative HIV-1 DNA polymerase chain reaction assay (Amplicor HIV-1 Monitor, version 1.5). Infants were defined as infected with HIV-1 if they had a detectable viral load > 10 000 copies/ml or were positive on DNA testing or both. Mothers’ HIV status was determined from their medical records. Women and their infants were recruited prior to or within a few days after delivery and followed until 3 to 4 weeks post-delivery. However, in cases where a mother was recorded as HIV-positive but had no detectable viral load, a repeat enzyme-linked immunosorbent assay was done to check for false positives (Vironostika HIV Uni-form II) followed by Access HIV-1/2 new assay (Bio-Rad). When HIV transmission was calculated, infants born to false-positive mothers were removed from the analysis. Quantitative data were entered into a Microsoft Access database using double data entry at a central site (Medical Research Council, Durban). After validation the database was exported to Stata statistical software, version 8.0, for data management and analysis. Comparisons of variables across sites were carried out using χ² tests for categorical variables and one-way analysis of variance for continuous variables (with the exception of income, which was compared using a Kruskal–Wallis test). No adjustments were made for multiple testing because the comparison between sites was viewed as descriptive rather than inferential. All factors in Tables 1 and and22 were examined as potential risk factors using logistic regression. To explain differences between the sites, variables were retained in the models if they were either at least of marginal significance or played a confounding role – that is, inclusion of the variable had a noticeable effect (> 10% change) – on the between-site odds ratios. a Values are age in years (standard deviation).b Values are number (percentage).c Values are mean log viral load (standard deviation).d Values are median income (interquartile range).e Values are mean score (standard deviation). Higher scores of socioeconomic status denote people who have more assets and food security.f Values are number of weeks (standard deviation).g Values are weight in grams (standard deviation).h Values are number with low birth weight (percentage). a Values are mean number (standard deviation).b Values are numerator (percentage).c Values are mean age in weeks (standard deviation).d Values are mean score (standard deviation). Details of the counselling index are given in the Methods section.e Delivery complications are defined as intrapartum haemorrhage, gestational proteinuric hypertension, eclampsia, cephalopelvic disproportion, poor labour, chorioamnionitis, fever, meconium liquor and fetal distress.f Details of the protocol are given in the Methods section.g Values are mean number of days (standard deviation). Ethical approval was obtained from the University of KwaZulu–Natal and permission was obtained from participating institutions. Signed informed consent was obtained at the time of enrolment into the study. All staff signed a confidentiality agreement. Compensation offered to participants for their time was site-specific and took the form of cash (Umlazi), food vouchers (Paarl) or food parcels (Rietvlei).

AI Digest

Study Justification:

The study aimed to determine the operational effectiveness of the South African program for preventing mother-to-child transmission (PMTCT) of HIV in reducing rates of early transmission of infection. This was important because it provided valuable information on the real-world effectiveness of the program in a diverse range of settings.

Study Highlights:

– The study included 665 mother-infant pairs who participated in the South African PMTCT program between October 2002 and November 2004.
– Three sites in different provinces were selected to represent differences in socioeconomic status and HIV prevalence.
– Rates of early HIV transmission ranged from 8.6% to 13.7%.
– Maternal viral load was the only statistically significant risk factor for transmission.
– After adjusting for maternal viral load and prevalence of low birth weight, the odds of transmission were 1.8 times higher at the rural site.
– Controlling for antenatal visits and delivery complications reduced the odds of transmission to 1.5 times higher at the rural site.
– Rates of early transmission of HIV using single-dose nevirapine were similar to those obtained in clinical trials.
– Scaling up access to antiretroviral regimens for women will further reduce transmission to infants.

Study Recommendations:

Based on the findings, the study recommends:

– Scaling up access to antiretroviral regimens for women to further reduce transmission of HIV to infants.
– Improving the quality of antenatal care and labor ward care, particularly in rural areas, to reduce the risk of transmission.
– Enhancing counseling services to ensure that women receive comprehensive information about the risk of mother-to-child transmission and feeding options for their infants.

Key Role Players:

– Health policymakers and government officials responsible for implementing and funding HIV prevention programs.
– Healthcare providers, including doctors, nurses, and midwives, who play a crucial role in delivering antenatal care and labor ward care.
– Community health workers who can provide education and support to pregnant women and new mothers.
– Researchers and scientists who can continue to study and evaluate the effectiveness of PMTCT programs.

Cost Items for Planning Recommendations:

– Antiretroviral medications for pregnant women.
– Training and capacity building for healthcare providers.
– Counseling services and educational materials for pregnant women.
– Monitoring and evaluation of PMTCT programs.
– Infrastructure and equipment for antenatal care and labor ward care facilities.
– Community outreach and support programs.
– Research and data collection to assess the impact of interventions.
Please note that the cost items provided are general categories and not actual cost estimates. The actual costs will depend on the specific context and implementation strategy.

Strength of Evidence

The strength of evidence for this abstract is 7 out of 10.
The evidence in the abstract is based on a prospective cohort study with a large sample size, which adds strength to the findings. The study includes data from multiple sites with varying socioeconomic status and HIV prevalence, increasing the generalizability of the results. However, the study does not mention randomization or blinding, which are important factors for minimizing bias. To improve the evidence, future studies could consider randomizing participants and implementing blinding techniques to reduce potential biases.

Abstract

This was a prospective cohort study of mothers and infants seen at three of the 18 national prevention programme pilot sites in South Africa between October 2002 and November 2004. Women were recruited at the health facility either before delivery or within a few days after delivery; they were visited again at 3 to 4 weeks post-delivery. Three areas (the main towns of Paarl and Rietvlei and the dormitory township of Umlazi) were selected to reflect different socioeconomic regions, rural and urban locations and antenatal prevalence rates of HIV. Paarl, in the Western Cape province, is a relatively well-resourced periurban and rural area with a well-functioning health system and a 2004 antenatal HIV prevalence of 9%.12 Rietvlei, a rural area in the Eastern Cape province, is in one of the poorest parts of South Africa and its antenatal HIV prevalence in 2004 was 28%.12 Umlazi, near the port of Durban in KwaZulu–Natal, is a periurban area with formal and informal housing. The socioeconomic status of residents is similar to that in Paarl but the health systems are weaker and the antenatal HIV prevalence in 2004 was 47%.12 All data were collected by trained field researchers. Mothers were interviewed using semistructured interviews at the time of recruitment and during the follow-up visit at 3 to 4 weeks. Topics covered included the extent of antenatal care received, plans for disclosure of HIV status and basic knowledge of HIV/AIDS and of mother-to-child transmission. Obstetric records were reviewed using a record review capture sheet to obtain data on antenatal and intrapartum risk factors for transmission. All interviews were conducted in the preferred language of the participant (Afrikaans, English, Xhosa or Zulu). Nevirapine was considered to have been taken by the mother according to protocol if it was taken between 2 and 24 hours before delivery; nevirapine was considered to have been administered to infants according to protocol if it was given within 72 hours after birth. A measure of socioeconomic status was devised using principal component factor analysis that included six household assets (presence of refrigerator, radio, television, stove, telephone or mobile phone, car) and a question regarding food security. This produced a weighted average, so items with a greater variability (e.g. television) contribute more to the score than items with a lesser variability (e.g. radio). The counselling index measured whether the following three topics were mentioned by the counsellor, nurse or midwife during the woman’s pregnancy (as recalled by the woman): the risk of mother-to-child transmission and breastfeeding, how women could choose the best method to feed their infant, and whether the advantages and disadvantages of feeding options were discussed and the woman was helped to make a suitable choice. For each topic a score of 1 was allocated if the topic was covered. If a mother recalled that she was simply told to formula-feed or to breastfeed, then the general counselling index for that mother was decreased by 1 point. Thus, scores on the counselling index ranged from –1 to 3. During the home visit at 3 to 4 weeks post-delivery, trained field staff collected blood spots on Guthrie cards from all infants and mothers by means of a heel or finger prick. Following overnight drying, the filter paper was inserted into a self-sealing envelope with desiccant. Blood specimens were couriered to the laboratory for analysis. HIV infection in infants was determined from dried blood spots using an HIV-1 RNA quantitation assay (nucleic acid sequence-based amplification with electro chemiluminescent detection, NucliSens HIV-1 QT) with a lower detection limit of 80 copies of HIV RNA per ml of blood (equivalent to 1600 copies HIV RNA per 50 μL dried blood spot)13 and a qualitative HIV-1 DNA polymerase chain reaction assay (Amplicor HIV-1 Monitor, version 1.5). Infants were defined as infected with HIV-1 if they had a detectable viral load > 10 000 copies/ml or were positive on DNA testing or both. Mothers’ HIV status was determined from their medical records. Women and their infants were recruited prior to or within a few days after delivery and followed until 3 to 4 weeks post-delivery. However, in cases where a mother was recorded as HIV-positive but had no detectable viral load, a repeat enzyme-linked immunosorbent assay was done to check for false positives (Vironostika HIV Uni-form II) followed by Access HIV-1/2 new assay (Bio-Rad). When HIV transmission was calculated, infants born to false-positive mothers were removed from the analysis. Quantitative data were entered into a Microsoft Access database using double data entry at a central site (Medical Research Council, Durban). After validation the database was exported to Stata statistical software, version 8.0, for data management and analysis. Comparisons of variables across sites were carried out using χ² tests for categorical variables and one-way analysis of variance for continuous variables (with the exception of income, which was compared using a Kruskal–Wallis test). No adjustments were made for multiple testing because the comparison between sites was viewed as descriptive rather than inferential. All factors in Tables 1 and and22 were examined as potential risk factors using logistic regression. To explain differences between the sites, variables were retained in the models if they were either at least of marginal significance or played a confounding role – that is, inclusion of the variable had a noticeable effect (> 10% change) – on the between-site odds ratios. a Values are age in years (standard deviation).b Values are number (percentage).c Values are mean log viral load (standard deviation).d Values are median income (interquartile range).e Values are mean score (standard deviation). Higher scores of socioeconomic status denote people who have more assets and food security.f Values are number of weeks (standard deviation).g Values are weight in grams (standard deviation).h Values are number with low birth weight (percentage). a Values are mean number (standard deviation).b Values are numerator (percentage).c Values are mean age in weeks (standard deviation).d Values are mean score (standard deviation). Details of the counselling index are given in the Methods section.e Delivery complications are defined as intrapartum haemorrhage, gestational proteinuric hypertension, eclampsia, cephalopelvic disproportion, poor labour, chorioamnionitis, fever, meconium liquor and fetal distress.f Details of the protocol are given in the Methods section.g Values are mean number of days (standard deviation). Ethical approval was obtained from the University of KwaZulu–Natal and permission was obtained from participating institutions. Signed informed consent was obtained at the time of enrolment into the study. All staff signed a confidentiality agreement. Compensation offered to participants for their time was site-specific and took the form of cash (Umlazi), food vouchers (Paarl) or food parcels (Rietvlei).

Materials

N/A

Innovations

Based on the provided information, here are some potential innovations that can be used to improve access to maternal health:

1. Mobile Health (mHealth) Applications: Develop and implement mobile applications that provide information and support to pregnant women, such as reminders for prenatal care appointments, educational resources on maternal health, and access to telemedicine consultations.

2. Community Health Workers: Train and deploy community health workers to provide maternal health education, counseling, and support to pregnant women in underserved areas. These workers can also assist in identifying and referring high-risk pregnancies for appropriate care.

3. Telemedicine Services: Establish telemedicine services that allow pregnant women in remote or rural areas to consult with healthcare providers and receive prenatal care remotely. This can help overcome geographical barriers and improve access to specialized care.

4. Transportation Support: Develop transportation programs or partnerships to provide pregnant women with reliable and affordable transportation to healthcare facilities for prenatal care visits, delivery, and postnatal care.

5. Task-Shifting: Train and empower non-specialist healthcare providers, such as nurses and midwives, to perform certain tasks traditionally done by doctors. This can help alleviate the shortage of healthcare professionals and improve access to maternal health services.

6. Integration of Services: Implement integrated healthcare models that combine maternal health services with other essential healthcare services, such as family planning, HIV testing and treatment, and nutrition support. This can improve efficiency and accessibility of care.

7. Health Information Systems: Strengthen health information systems to collect, analyze, and utilize data on maternal health outcomes and service utilization. This can help identify gaps in access and quality of care, and inform evidence-based decision-making for improvement.

8. Public-Private Partnerships: Foster collaborations between public and private sectors to leverage resources and expertise in improving access to maternal health services. This can include partnerships with private healthcare providers, pharmaceutical companies, and technology companies.

9. Financial Support: Develop and implement innovative financing mechanisms, such as health insurance schemes or conditional cash transfer programs, to reduce financial barriers to accessing maternal health services.

10. Quality Improvement Initiatives: Implement quality improvement initiatives that focus on improving the quality of care provided during pregnancy, childbirth, and postnatal period. This can include training healthcare providers, improving infrastructure and equipment, and implementing evidence-based clinical guidelines.

These innovations can help address barriers to accessing maternal health services and improve the overall quality of care for pregnant women.

AI Innovations Description

Based on the information provided, the recommendation to improve access to maternal health and prevent mother-to-child transmission of HIV is to scale up access to antiretroviral regimens for women. This recommendation is based on the findings of the study, which showed that rates of early transmission of HIV in an operational setting using single-dose nevirapine administered to both mother and child were similar to those obtained in clinical trials. By increasing access to antiretroviral regimens, more women can receive the necessary treatment to reduce the risk of transmission to their infants. This can be achieved through the expansion of prevention of mother-to-child transmission (PMTCT) programs and ensuring that antiretroviral medications are readily available and accessible to pregnant women.

AI Innovations Methodology

Based on the provided information, here are some potential recommendations for improving access to maternal health:

1. Strengthening Health Systems: Enhance the capacity and resources of health facilities in rural and periurban areas, such as Umlazi, to provide comprehensive maternal health services. This includes improving infrastructure, ensuring availability of skilled healthcare providers, and adequate medical supplies.

2. Community-Based Interventions: Implement community-based programs to increase awareness and knowledge about maternal health, HIV prevention, and mother-to-child transmission. This can involve training community health workers to provide education, counseling, and support to pregnant women and new mothers.

3. Mobile Health (mHealth) Solutions: Utilize mobile technology to improve access to maternal health services, especially in remote areas. This can include mobile apps for appointment reminders, health information, and telemedicine consultations.

4. Integration of Services: Integrate maternal health services with other existing healthcare programs, such as HIV/AIDS prevention and treatment, to provide comprehensive care to pregnant women and reduce stigma associated with seeking specific services.

To simulate the impact of these recommendations on improving access to maternal health, a methodology could include the following steps:

1. Baseline Data Collection: Gather data on the current state of maternal health access, including factors such as healthcare utilization, availability of services, and barriers faced by pregnant women.

2. Define Key Indicators: Identify specific indicators that reflect improved access to maternal health, such as the number of antenatal care visits, percentage of women receiving HIV testing and counseling, and rates of early HIV transmission.

3. Develop a Simulation Model: Create a mathematical or statistical model that incorporates the identified recommendations and their potential impact on the key indicators. This model should consider factors such as population demographics, healthcare infrastructure, and resource allocation.

4. Input Data and Parameters: Input the collected baseline data and relevant parameters into the simulation model. This may include data on population size, healthcare facility capacity, and the expected effectiveness of each recommendation.

5. Run Simulations: Run multiple simulations using different scenarios and assumptions to assess the potential impact of the recommendations on improving access to maternal health. This can help identify the most effective strategies and estimate the magnitude of change in the key indicators.

6. Analyze Results: Analyze the simulation results to determine the projected impact of the recommendations on improving access to maternal health. This can include comparing different scenarios, identifying potential challenges or limitations, and assessing the feasibility of implementing the recommendations.

7. Refine and Implement: Based on the simulation findings, refine the recommendations and develop an implementation plan. This may involve prioritizing specific interventions, allocating resources, and establishing monitoring and evaluation mechanisms to track progress and make necessary adjustments.

By following this methodology, policymakers and healthcare providers can gain insights into the potential impact of different recommendations on improving access to maternal health and make informed decisions to prioritize and implement effective interventions.

Author

Dima Health

Statistics:

Citations: 28

Identifiers:

DOI: 10.2471/BLT.06.033639

ISSN: 00429686

Research Areas:

Community Interventions, Food Security, Genetics and Genomics, Health System and Policy, Infectious Diseases, Maternal Access, Maternal and Child Health, Noncommunicable Diseases, Quality of Care, Sexual and Reproductive Health, Social Determinants

Study Countries:

South Africa

Study Design:

Cohort Study, Cross Sectional Study

Study Approach:

Mixed-methods, Qualitative, Quantitative

Participants Gender:

Female