National-level effectiveness of ART to prevent early mother to child transmission of HIV in Namibia

PLoS ONE, Volume 15, No. 11 November, Year 2020

Interpretation

Background Namibia introduced the prevention of mother to child HIV transmission (MTCT) program in 2002 and lifelong antiretroviral therapy (ART) for pregnant women (option B-plus) in 2013. We sought to quantify MTCT measured at 4-12 weeks post-delivery. Methods During Aug 2014-Feb 2015, we recruited a nationally representative sample of 1040 pairs of mother and infant aged 4-12 weeks at routine immunizations in 60 public health clinics using two stage sampling approach. Of these, 864 HIV exposed infants had DNA-PCR HIV test results available. We defined an HIV exposed infant if born to an HIV-positive mother with documented status or diagnosed at enrollment using rapid HIV tests. Dried Blood Spots samples from HIV exposed infants were tested for HIV. Interview data and laboratory results were collected on smartphones and uploaded to a central database. We measured MTCT prevalence at 4-12 weeks post-delivery and evaluated associations between infant HIV infection and maternal and infant characteristics including maternal treatment and infant prophylaxis. All statistical analyses accounted for the survey design. Results Based on the 864 HIV exposed infants with test results available, nationally weighted early MTCT measured at 4-12 weeks post-delivery was 1.74% (95% confidence interval (CI): 1.00%-3.01%). Overall, 62% of mothers started ART pre-conception, 33.6% during pregnancy, 1.2% post-delivery and 3.2% never received ART. Mothers who started ART before pregnancy and during pregnancy had low MTCT prevalence, 0.78% (95% CI: 0.31%-1.96%) and 0.98% (95% CI: 0.33%-2.91%), respectively. MTCT rose to 4.13% (95% CI: 0.54%-25.68%) when the mother started ART after delivery and to 11.62% (95% CI: 4.07%-28.96%) when she never received ART. The lowest MTCT of 0.76% (95% CI: 0.36%-1.61%) was achieved when mother received ART and ARV prophylaxis within 72hrs for infant and highest 22.32% (95%CI: 2.78%-74.25%) when neither mother nor infant received ARVs. After adjusting for mother’s age, maternal ART (Prevalence Ratio (PR) = 0.10, 95% CI: 0.03-0.29) and infant ARV prophylaxis (PR = 0.32, 95% CI: 0.10-0.998) remained strong predictors of HIV transmission. Conclusion As of 2015, Namibia achieved MTCT of 1.74%, measured at 4-12 weeks post-delivery. Women already on ART pre-conception had the lowest prevalence of MTCT emphasizing the importance of early HIV diagnosis and treatment initiation before pregnancy. Studies are needed to measure MTCT and maternal HIV seroconversion during breastfeeding. We conducted a cross–sectional clinic-based survey assessing uptake of ART among HIV infected mothers and MTCT prevalence among their HIV exposed infants 4–12 weeks of age. We recruited caregivers (hereafter referred to as mothers) and their infants from those seeking routine immunization or postnatal care services in 60 selected public health facilities between August 2014 and February 2015. We used a two-stage sampling method to recruit participants for this study. The sampling frame for the primary sampling unit was composed of public health facilities offering routine primary health care services to mothers and children throughout Namibia. We stratified all 326 public health facilities providing routine vaccination into five strata based on quintiles of the number of first doses of DPT vaccine administered during 2012, which was used as a measure of size of the number of infants that received care at each facility. Due to the feasibility and logistics of recruiting participants from the least visited clinics in the first quintile, we excluded this stratum from our sampling frame. This stratum contained 67 clinics, which accounted for 1.4% (841/62,088) of first doses of DPT vaccine administered across all clinics. In the first stage of sampling, within each of the four remaining sampling strata we randomly selected 15 health facilities, for a total of 60 facilities (23% of all eligible facilities). The selected facilities covered all 13 regions in Namibia. In the second stage, we recruited and enrolled all eligible and consenting caregiver-infant pairs in each facility for 19 consecutive weeks. The sampling weight for each caregiver-infant pair was calculated as the inverse of the probability of selection, defined as the probability of selecting the health facility in the first stage multiplied by the probability of selecting an HIV-exposed infant with test results in the selected health facility in the second stage. The second stage probability was based on the number of first doses of DPT vaccine administered during 2014 to reflect the total population of infants receiving care at all of the facilities at the time of sampling. HIV-exposed infants age 4–12 weeks were identified by maternal HIV infection status. We included women with a documented HIV positive status on either the ANC card or health passport and identified new positives by testing all women with a previous negative or unknown status per national testing guidelines. We excluded severely ill infants, infants whose mothers refused consent and those younger than 4 weeks or older than 12 weeks. We trained nurses at site level to identify all potentially eligible mother-infant pairs and work with trained data collectors to complete a standardized screening and interview questionnaire. We screened mother-infant pairs in two steps: (1) ensure the child was not brought to the health facility for emergency medical care and the child had not already been enrolled in the study, and (2) include only infants aged 4–12 weeks and mothers who consented for the study. For those who met these inclusion criteria, and provided written consent to participate in the study, we used the standardized questionnaire to gather sociodemographic data, clinical, treatment, and feeding data from the mother-infant pair. In addition to interviewing the mother, some clinical information was extracted from the maternal ANC cards and the infant child health passports (maternal HIV status, maternal ART use, infant HIV exposure status, and infant ARV prophylaxis). Study nurses recorded infant HIV PCR tests and results in routine MOHSS clinic registers at each site. Confidential participant identification numbers were recorded in the study register(s) for infants/mothers enrolled in the study. The participant identification number was placed on the dried blood spot card, the laboratory request form, and the questionnaire. All interview data and laboratory results were collected on password protected smartphones and uploaded daily to a secure central database. The clinic healthcare providers conducted pre- and post-test counselling and delivered HIV test results to the mother-infant pairs as per standard clinic procedures. Mothers with an unknown or previous HIV negative status were tested using parallel HIV rapid tests. Discordant results between two rapid tests were confirmed by a third rapid test (tiebreaker). All rapid HIV tests were done at the study health facilities by trained health workers. Trained nurses collected blood samples from HIV exposed-infants whose mothers consented for infant’s HIV test on a 5-spot Guthrie card as dried blood spots. All dried blood spot specimens accompanied by routine laboratory request forms were sent to the central laboratory for HIV DNA PCR testing using COBAS AmpliPrep/COBAS TaqMan HIV-1 Qualitative Test version 2.0. Infant’s dried blood spot DNA PCR HIV test results were returned to the mother within 2–4 weeks of testing. Prior to participation, eligible mothers were read an information sheet including study procedures and confidentiality and asked to sign written informed consent prior to participation. The participant identification numbers were used to link the mother’s and infant’s information and to provide the infant’s HIV test results to be used for clinical care. The participant identification number, name, phone number, home address and direction to home that were collected with the mother’s consent were kept in a locked box at the facility only accessed by the facility nurse and data collector. HIV test results were returned to the mother or legal guardian by clinic nurses who complied with the national guidelines. All data collectors and supervisors were trained on confidentiality procedures and signed a confidentiality agreement. All electronic survey data were encrypted. The study was approved by Namibia’s Ministry of Health and Social Services research ethical committees. The study was also reviewed in accordance with CDC human research protection procedures and was determined to be research, but CDC investigators did not interact with human subjects or have access to identifiable data or specimens for research purposes. We calculated descriptive statistics for maternal and infant characteristics. We calculated the weighted estimate of the national prevalence of early MTCT at 4–12 weeks and 95% confidence interval (CI). To determine importance of timing of maternal ART, we categorized self-reported maternal ART into four groups of maternal ART initiation timing: before pregnancy, during pregnancy (including delivery), after delivery, or mother never received ART. To assess additional benefit of infant prophylaxis, we also created a composite factor for maternal ART and infant ARV prophylaxis: mother received ART and infant received ARV prophylaxis, mother received ART but infant did not receive ARV prophylaxis, mother did not receive ART and infant received ARV prophylaxis, or neither received ART/ARV. For categories of each maternal and infant characteristic, we estimated the prevalence of MTCT and 95% CI. To evaluate the association between each maternal/infant characteristic and/or PMTCT intervention and the ultimate outcome-infant HIV infection, we performed the design-based Pearson’s chi-square test. For evaluating each association, we fit a Poisson regression model to calculate prevalence ratios and 95% CIs [13]. Characteristics with a p-value less than 0.20 were considered for a multivariable Poisson regression model. Statistical significance was assessed at the 0.05 level for all analyses. All analyses were performed using Stata software version 14.2 and accounted for the two-stage survey design and sampling weights (svyset command).

AI Digest

Study Justification:

– The study aimed to assess the effectiveness of antiretroviral therapy (ART) in preventing early mother-to-child transmission (MTCT) of HIV in Namibia.
– The study was conducted to provide evidence on the impact of Namibia’s prevention of MTCT program and lifelong ART for pregnant women.
– The findings of the study would help inform policy decisions and interventions to further reduce MTCT of HIV in Namibia.

Highlights:

– The study recruited a nationally representative sample of 1040 pairs of mother and infant aged 4-12 weeks at routine immunizations in 60 public health clinics.
– Of the 864 HIV exposed infants with available test results, the nationally weighted early MTCT prevalence measured at 4-12 weeks post-delivery was 1.74%.
– Mothers who started ART before pregnancy and during pregnancy had the lowest MTCT prevalence, emphasizing the importance of early HIV diagnosis and treatment initiation before pregnancy.
– Maternal ART and infant ARV prophylaxis were strong predictors of HIV transmission, with lower prevalence observed when both interventions were received.

Recommendations:

– Continue promoting early HIV diagnosis and treatment initiation before pregnancy to reduce MTCT of HIV.
– Ensure access to ART for all HIV-positive pregnant women, with a focus on initiating treatment before or during pregnancy.
– Strengthen implementation of infant ARV prophylaxis to further reduce MTCT of HIV.
– Conduct further studies to measure MTCT and maternal HIV seroconversion during breastfeeding.

Key Role Players:

– Ministry of Health and Social Services
– Public health facilities
– Nurses and healthcare providers
– Data collectors and supervisors
– Laboratory personnel

Cost Items for Planning Recommendations:

– Training of nurses and healthcare providers on HIV testing, counseling, and treatment protocols
– Procurement and distribution of antiretroviral drugs for pregnant women and infants
– Laboratory testing and equipment for HIV diagnosis and monitoring
– Data collection and management systems, including smartphones and secure central database
– Monitoring and evaluation activities to assess the impact of interventions

Strength of Evidence

The strength of evidence for this abstract is 8 out of 10.
The evidence in the abstract is strong, but there are some areas for improvement. The study design is cross-sectional and clinic-based, which may limit generalizability. Additionally, the sample size of 1040 pairs of mother and infant is relatively small. To improve the evidence, future studies could consider using a larger sample size and a longitudinal design to assess the long-term effectiveness of ART in preventing early mother to child transmission of HIV.

Abstract

We conducted a cross–sectional clinic-based survey assessing uptake of ART among HIV infected mothers and MTCT prevalence among their HIV exposed infants 4–12 weeks of age. We recruited caregivers (hereafter referred to as mothers) and their infants from those seeking routine immunization or postnatal care services in 60 selected public health facilities between August 2014 and February 2015. We used a two-stage sampling method to recruit participants for this study. The sampling frame for the primary sampling unit was composed of public health facilities offering routine primary health care services to mothers and children throughout Namibia. We stratified all 326 public health facilities providing routine vaccination into five strata based on quintiles of the number of first doses of DPT vaccine administered during 2012, which was used as a measure of size of the number of infants that received care at each facility. Due to the feasibility and logistics of recruiting participants from the least visited clinics in the first quintile, we excluded this stratum from our sampling frame. This stratum contained 67 clinics, which accounted for 1.4% (841/62,088) of first doses of DPT vaccine administered across all clinics. In the first stage of sampling, within each of the four remaining sampling strata we randomly selected 15 health facilities, for a total of 60 facilities (23% of all eligible facilities). The selected facilities covered all 13 regions in Namibia. In the second stage, we recruited and enrolled all eligible and consenting caregiver-infant pairs in each facility for 19 consecutive weeks. The sampling weight for each caregiver-infant pair was calculated as the inverse of the probability of selection, defined as the probability of selecting the health facility in the first stage multiplied by the probability of selecting an HIV-exposed infant with test results in the selected health facility in the second stage. The second stage probability was based on the number of first doses of DPT vaccine administered during 2014 to reflect the total population of infants receiving care at all of the facilities at the time of sampling. HIV-exposed infants age 4–12 weeks were identified by maternal HIV infection status. We included women with a documented HIV positive status on either the ANC card or health passport and identified new positives by testing all women with a previous negative or unknown status per national testing guidelines. We excluded severely ill infants, infants whose mothers refused consent and those younger than 4 weeks or older than 12 weeks. We trained nurses at site level to identify all potentially eligible mother-infant pairs and work with trained data collectors to complete a standardized screening and interview questionnaire. We screened mother-infant pairs in two steps: (1) ensure the child was not brought to the health facility for emergency medical care and the child had not already been enrolled in the study, and (2) include only infants aged 4–12 weeks and mothers who consented for the study. For those who met these inclusion criteria, and provided written consent to participate in the study, we used the standardized questionnaire to gather sociodemographic data, clinical, treatment, and feeding data from the mother-infant pair. In addition to interviewing the mother, some clinical information was extracted from the maternal ANC cards and the infant child health passports (maternal HIV status, maternal ART use, infant HIV exposure status, and infant ARV prophylaxis). Study nurses recorded infant HIV PCR tests and results in routine MOHSS clinic registers at each site. Confidential participant identification numbers were recorded in the study register(s) for infants/mothers enrolled in the study. The participant identification number was placed on the dried blood spot card, the laboratory request form, and the questionnaire. All interview data and laboratory results were collected on password protected smartphones and uploaded daily to a secure central database. The clinic healthcare providers conducted pre- and post-test counselling and delivered HIV test results to the mother-infant pairs as per standard clinic procedures. Mothers with an unknown or previous HIV negative status were tested using parallel HIV rapid tests. Discordant results between two rapid tests were confirmed by a third rapid test (tiebreaker). All rapid HIV tests were done at the study health facilities by trained health workers. Trained nurses collected blood samples from HIV exposed-infants whose mothers consented for infant’s HIV test on a 5-spot Guthrie card as dried blood spots. All dried blood spot specimens accompanied by routine laboratory request forms were sent to the central laboratory for HIV DNA PCR testing using COBAS AmpliPrep/COBAS TaqMan HIV-1 Qualitative Test version 2.0. Infant’s dried blood spot DNA PCR HIV test results were returned to the mother within 2–4 weeks of testing. Prior to participation, eligible mothers were read an information sheet including study procedures and confidentiality and asked to sign written informed consent prior to participation. The participant identification numbers were used to link the mother’s and infant’s information and to provide the infant’s HIV test results to be used for clinical care. The participant identification number, name, phone number, home address and direction to home that were collected with the mother’s consent were kept in a locked box at the facility only accessed by the facility nurse and data collector. HIV test results were returned to the mother or legal guardian by clinic nurses who complied with the national guidelines. All data collectors and supervisors were trained on confidentiality procedures and signed a confidentiality agreement. All electronic survey data were encrypted. The study was approved by Namibia’s Ministry of Health and Social Services research ethical committees. The study was also reviewed in accordance with CDC human research protection procedures and was determined to be research, but CDC investigators did not interact with human subjects or have access to identifiable data or specimens for research purposes. We calculated descriptive statistics for maternal and infant characteristics. We calculated the weighted estimate of the national prevalence of early MTCT at 4–12 weeks and 95% confidence interval (CI). To determine importance of timing of maternal ART, we categorized self-reported maternal ART into four groups of maternal ART initiation timing: before pregnancy, during pregnancy (including delivery), after delivery, or mother never received ART. To assess additional benefit of infant prophylaxis, we also created a composite factor for maternal ART and infant ARV prophylaxis: mother received ART and infant received ARV prophylaxis, mother received ART but infant did not receive ARV prophylaxis, mother did not receive ART and infant received ARV prophylaxis, or neither received ART/ARV. For categories of each maternal and infant characteristic, we estimated the prevalence of MTCT and 95% CI. To evaluate the association between each maternal/infant characteristic and/or PMTCT intervention and the ultimate outcome-infant HIV infection, we performed the design-based Pearson’s chi-square test. For evaluating each association, we fit a Poisson regression model to calculate prevalence ratios and 95% CIs [13]. Characteristics with a p-value less than 0.20 were considered for a multivariable Poisson regression model. Statistical significance was assessed at the 0.05 level for all analyses. All analyses were performed using Stata software version 14.2 and accounted for the two-stage survey design and sampling weights (svyset command).

Materials

N/A

Innovations

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

1. Mobile Health (mHealth) Technology: The use of smartphones and mobile applications to collect and upload interview data and laboratory results to a central database can improve data management and accessibility, allowing for more efficient and timely decision-making.

2. Point-of-Care Testing: Implementing point-of-care HIV testing technologies, such as rapid HIV tests, can provide immediate results to mothers, reducing the time and effort required for testing and improving access to early diagnosis and treatment.

3. Integrated Care: Integrating maternal health services with routine immunization or postnatal care services can increase access to maternal health interventions, as mothers and infants are more likely to seek care at these facilities.

4. Training and Capacity Building: Providing training to healthcare providers on maternal health interventions, including HIV prevention and treatment, can improve the quality of care and increase access to appropriate interventions.

5. Community Engagement: Engaging communities through awareness campaigns, education programs, and community-based support groups can help increase knowledge and understanding of maternal health issues, reduce stigma, and encourage early testing and treatment.

6. Strengthening Health Systems: Investing in health system strengthening, including infrastructure development, supply chain management, and human resource capacity, can improve access to maternal health services and ensure the availability of necessary resources.

It is important to note that these recommendations are based on the specific context of Namibia and the information provided. Further research and evaluation would be needed to determine the feasibility and effectiveness of these innovations in improving access to maternal health in Namibia.

AI Innovations Description

The study conducted in Namibia aimed to assess the effectiveness of antiretroviral therapy (ART) in preventing early mother-to-child transmission (MTCT) of HIV. The study recruited a nationally representative sample of 1040 pairs of mothers and infants aged 4-12 weeks at routine immunizations in 60 public health clinics. The study found that the nationally weighted early MTCT prevalence at 4-12 weeks post-delivery was 1.74%.

Based on the findings, the following recommendations can be made to improve access to maternal health and further reduce MTCT:

1. Early HIV diagnosis and treatment initiation: The study emphasized the importance of early HIV diagnosis and treatment initiation before pregnancy. Encouraging women to get tested for HIV and start ART early can significantly reduce the risk of MTCT.

2. Strengthening ART coverage: The study found that mothers who started ART before pregnancy and during pregnancy had the lowest prevalence of MTCT. Efforts should be made to ensure that all HIV-positive pregnant women have access to ART and receive it in a timely manner.

3. Improving access to ARV prophylaxis for infants: The study found that the lowest MTCT prevalence was achieved when both the mother received ART and the infant received ARV prophylaxis within 72 hours. Ensuring that infants born to HIV-positive mothers receive ARV prophylaxis in a timely manner can further reduce the risk of MTCT.

4. Enhancing HIV testing and counseling services: To identify HIV-positive pregnant women and provide them with appropriate care and treatment, it is crucial to strengthen HIV testing and counseling services. This includes promoting routine HIV testing during antenatal care visits and ensuring that all pregnant women have access to accurate and timely HIV test results.

5. Continued monitoring and evaluation: Regular monitoring and evaluation of MTCT prevalence and the effectiveness of interventions are essential to identify gaps and make informed decisions for further improvement. Ongoing research and studies should be conducted to measure MTCT and maternal HIV seroconversion during breastfeeding.

By implementing these recommendations, access to maternal health can be improved, and the risk of MTCT can be further reduced, ultimately contributing to better maternal and child health outcomes.

AI Innovations Methodology

The study described in the provided text aimed to assess the effectiveness of antiretroviral therapy (ART) in preventing early mother-to-child transmission (MTCT) of HIV in Namibia. The methodology used in the study involved recruiting a nationally representative sample of 1040 pairs of mother and infant aged 4-12 weeks at routine immunizations in 60 public health clinics. The sampling was conducted using a two-stage sampling approach, with the selection of health facilities in the first stage and the recruitment of participants in the second stage. The study collected interview data and laboratory results on smartphones, which were then uploaded to a central database. The prevalence of MTCT was measured at 4-12 weeks post-delivery, and associations between infant HIV infection and maternal and infant characteristics were evaluated.

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

1. Identify the recommendations: Based on the findings of the study and other relevant research, identify specific recommendations that could improve access to maternal health. These recommendations could include interventions such as increasing access to ART for pregnant women, improving antenatal care services, promoting early HIV diagnosis and treatment initiation, and enhancing infant prophylaxis.

2. Define the simulation model: Develop a simulation model that represents the current state of maternal health access and the potential impact of the identified recommendations. The model should consider factors such as the population size, healthcare infrastructure, availability of resources, and existing policies and programs related to maternal health.

3. Input data: Gather data on relevant variables, such as the number of pregnant women, HIV prevalence rates, healthcare facility capacities, and resource allocation for maternal health. This data will be used as input for the simulation model.

4. Implement the simulation: Use the simulation model to simulate the impact of the recommendations on improving access to maternal health. The model should consider different scenarios, such as the implementation of specific recommendations individually or in combination, and assess their potential effects on key outcomes, such as the reduction in MTCT prevalence, increase in ART coverage, and improvement in overall maternal health outcomes.

5. Analyze results: Analyze the simulation results to understand the potential impact of the recommendations on improving access to maternal health. Evaluate the effectiveness of different interventions and identify the most promising strategies for achieving the desired outcomes.

6. Refine and iterate: Based on the analysis of the simulation results, refine the recommendations and the simulation model if necessary. Repeat the simulation process to further explore the potential impact of refined recommendations and assess their feasibility and scalability.

By following this methodology, policymakers and healthcare stakeholders can gain insights into the potential impact of different recommendations on improving access to maternal health. This information can inform decision-making and help prioritize interventions that are most likely to have a positive impact on maternal health outcomes.

Author

Dima Health

Statistics:

Citations: 5

Identifiers:

DOI: 10.1371/journal.pone.0233341

Research Areas:

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

Study Countries:

Namibia

Study Design:

Cross Sectional Study, randomised-control-trial

Study Approach:

Mixed-methods, Qualitative, Quantitative

Participants Gender:

Female