Time to implement 9-month infant HIV testing in South Africa

Background. South Africa (SA) is likely to meet the National Strategic Plan target of <2% mother-to-child HIV transmission at 6 weeks of age in 2015. Children infected with HIV after 6 weeks often remain undiagnosed because of poor implementation of post-weaning and final outcome 18-month HIV testing. The World Health Organization recommends a screening HIV rapid test (HRT) in HIV-exposed infants at the 9-month immunisation visit to exclude postnatal infection, with a confirmatory HIV polymerase chain reaction (PCR) test if the HRT is positive.Objective. To evaluate the impact of substituting this recommendation for the post-weaning HIV testing recommended by SA guidelines.Methods. Rates of seroreversion and probability of infection at 9 months of age were applied to a theoretical population of 100 HIV-exposed infants, uninfected at birth and breastfed for 1 year with antiretroviral prophylaxis. Nine scenarios were developed and the number of HIV PCRs saved compared with current guidelines was calculated.Results. Nine-month testing using the HRT reduced the number of follow-up PCR tests done in all scenarios by >50%, with differences ranging from 51% to 59% and 81% to 89% for low and high seroreversion rates, respectively.Conclusions. Nine-month testing using HRT would increase identification and early treatment of HIV-infected infants, improve monitoring of postnatal transmission rates, and reduce the number of HIV PCR tests done with resultant cost saving. Training of healthcare workers implementing HRT would be required. Ongoing efforts to improve implementation and monitoring of testing at 9 and 18 months will be essential

Eliminating Vertical Transmission of HIV in South Africa: Establishing a Baseline for the Global Alliance to End AIDS in Children

To gain a detailed overview of vertical transmission in South Africa, we describe insights from the triangulation of data sources used to monitor the national HIV program. HIV PCR results from the National Health Laboratory Service (NHLS) were analysed from the National Institute of Communicable Diseases (NICD) data warehouse to describe HIV testing coverage and positivity among children <2 years old from 2017–2021. NICD data were compared and triangulated with the District Health Information System (DHIS) and the Thembisa 4.6 model. For 2021, Thembisa estimates a third of children living with HIV go undiagnosed, with NICD and DHIS data indicating low HIV testing coverage at 6 months (49%) and 18 months (33%) of age, respectively. As immunisation coverage is reported at 84% and 66% at these time points, better integration of HIV testing services within the Expanded Programme for Immunization is likely to yield improved case findings. Thembisa projects a gradual decrease in vertical transmission to 450 cases per 100,000 live births by 2030. Unless major advances and strengthening of maternal and child health services, including HIV prevention, diagnosis, and care, can be achieved, the goal to end AIDS in children by 2030 in South Africa is unlikely to be realised

KIR-HLA and Maternal-Infant HIV-1 Transmission in Sub-Saharan Africa

Numerous studies have suggested a role for natural killer (NK) cells in attenuation of HIV-1 disease progression via recognition by killer-cell immunoglobulin-like receptors (KIRs) of specific HLA class I molecules. The role of KIR and HLA class I has not been addressed in the context of maternal-infant HIV-1 transmission. KIR and HLA class I B and C genes from 224 HIV-1-infected mothers and 222 infants (72 infected and 150 uninfected) from South Africa were characterized. Although a number of significant associations were determined in both the total group and in the nevirapine (NVP) exposed group, the most significant findings involved KIR2DL2 and KIR2DL3 and HLA-C. KIR2DL2/KIR2DL3 was underrepresented in intrapartum (IP)-transmitting mothers compared to non-transmitting (NT) mothers (P = 0.008) and remained significant (P = 0.036) after correction for maternal viral load (MVL). Homozygosity for KIR2DL3 alone and in combination with HLA-C allotype heterozygosity (C1C2) was elevated in IP-transmitting mothers compared to NT mothers (P = 0.034 and P = 0.01 respectively), and after MVL correction (P = 0.033 and P = 0.027, respectively). In infants, KIR2DL3 in combination with its HLA-C1 ligand (C1) as well as homozygosity for KIR2DL3 with C1C2, were both found to be underrepresented in infected infants compared to exposed uninfected infants in the total group (P = 0.06 and P = 0.038, respectively) and in the sub-group of infants whose mothers received NVP (P = 0.007 and P = 0.03, respectively). These associations were stronger post MVL adjustment (total group: P = 0.02 and P = 0.009, respectively; NVP group: P = 0.004 and P = 0.02, respectively). Upon stratification according to low and high MVL, all significant associations fell within the low MVL group, suggesting that with low viral load, the effects of genotype can be more easily detected. In conclusion this study has identified a number of significant associations that suggest an important role for NK cells in maternal-to-infant HIV-1 transmission

A matter of context – time to clinically validate 9-month infant HIV testing in South Africa(?)

Mazanderani comments on an article by Fairlie at al. (September 2015 SAMJ)

KIR-HLA and Maternal-Infant HIV-1 Transmission in Sub-Saharan Africa

Numerous studies have suggested a role for natural killer (NK) cells in attenuation of HIV-1 disease progression via recognition by killer-cell immunoglobulin-like receptors (KIRs) of specific HLA class I molecules. The role of KIR and HLA class I has not been addressed in the context of maternal-infant HIV-1 transmission. KIR and HLA class I B and C genes from 224 HIV-1-infected mothers and 222 infants (72 infected and 150 uninfected) from South Africa were characterized. Although a number of significant associations were determined in both the total group and in the nevirapine (NVP) exposed group, the most significant findings involved KIR2DL2 and KIR2DL3 and HLA-C. KIR2DL2/KIR2DL3 was underrepresented in intrapartum (IP)-transmitting mothers compared to non-transmitting (NT) mothers (P = 0.008) and remained significant (P = 0.036) after correction for maternal viral load (MVL). Homozygosity for KIR2DL3 alone and in combination with HLA-C allotype heterozygosity (C1C2) was elevated in IP-transmitting mothers compared to NT mothers (P = 0.034 and P = 0.01 respectively), and after MVL correction (P = 0.033 and P = 0.027, respectively). In infants, KIR2DL3 in combination with its HLA-C1 ligand (C1) as well as homozygosity for KIR2DL3 with C1C2, were both found to be underrepresented in infected infants compared to exposed uninfected infants in the total group (P = 0.06 and P = 0.038, respectively) and in the sub-group of infants whose mothers received NVP (P = 0.007 and P = 0.03, respectively). These associations were stronger post MVL adjustment (total group: P = 0.02 and P = 0.009, respectively; NVP group: P = 0.004 and P = 0.02, respectively). Upon stratification according to low and high MVL, all significant associations fell within the low MVL group, suggesting that with low viral load, the effects of genotype can be more easily detected. In conclusion this study has identified a number of significant associations that suggest an important role for NK cells in maternal-to-infant HIV-1 transmission

An approach for evaluating early and long term mother-to-child transmission of HIV (MTCT) in low and middle income countries: a South African experience

Abstract Background Eliminating mother-to-child transmission of HIV is a global public health target. Robust, feasible methodologies to measure population level impact of programmes to prevent mother-to-child transmission of HIV (PMTCT) are needed in high HIV prevalence settings. We present a summary of the protocol of the South African PMTCT Evaluation (SAPMTCTE) with its revision over three repeated rounds of the survey, 2010–2014. Methods Three cross sectional surveys (2010, 2011–2012 and 2012–2013) were conducted in 580 primary health care immunisation service points randomly selected after stratified multistage probability proportional to size sampling. All infants aged 4–8 weeks receiving their six-week immunisation at a sampled facility on the day of the visit were eligible to participate. Trained research nurses conducted interviews and took infant dried blood spot (iDBS) samples for HIV enzyme immunoassay (EIA) and total nucleic acid polymerase chain reaction (PCR) testing. Interviews were conducted using mobile phones and iDBS were sent to the National Health Laboratory for testing. All findings were adjusted for study design, non-response, and weighted for number of South African live-birth in each study round. In 2012 a national closed cohort of these 4 to 8-week old infants testing EIA positive (HIV Exposed Infants) from the 2012–2013 cross-sectional survey was established to estimate longer-term PMTCT impact to 18 months. Follow-up analyses were to estimate weighted cumulative MTCT until 18 months, postnatal MTCT from 6 weeks until 18 months and a combined outcome of MTCT-or-death, using a competing risks model, with death as a competing risk. HIV-free survival was defined as a child surviving and HIV-negative up to 18 months or last visit seen. A weighted cumulative incidence analysis was conducted, adjusting for survey design effects. Discussion In the absence of robust high-quality routine medical recording systems, in the context of a generalised HIV epidemic, national surveys can be used to monitor PMTCT effectiveness; however, monitoring long-term outcomes nationally is difficult due to poor retention in care

Recommendations for the management of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme

Indeterminate HIV PCR results represent missed diagnostic opportunities within South Africa’s early infant diagnosis programme. These results not only delay diagnosis and appropriate management but are also a source of confusion and apprehension amongst clinicians and caregivers. We describe the extent of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme and provide recommendations for the management of these cases, both in terms of laboratory practice and the clinical care of the infants.They also thank the United Nations Children’s Emergency Fund (UNICEF) for partial funding of this work. A.H.M. acknowledges the Discovery Foundation for financial support.http://www.sajhivmed.org.zaam2016Medical Virolog

Elimination of mother-to-child transmission of HIV in South Africa : rapid scale-up using quality improvement

BACKGROUND. South Africa (SA) is committed to achieving the goal of eliminating mother-to-child transmission (MTCT) of HIV by 2015. To achieve this, universal coverage of quality antenatal, labour, delivery and postnatal services for all women has to be attained. Over the past decade, the prevention of mother-to-child transmission (PMTCT) programme has been scaled up to reach all healthcare facilities in the country. However, challenges persist in achieving 100% coverage and access to the programme. OBJECTIVES. We describe the process undertaken by the National Department of Health (NDoH), in collaboration with partners, to develop, implement and monitor a data-driven intervention to improve facility, district, provincial and national PMTCT-related performance. METHODS. Between 2011 and 2013, the NDoH developed and implemented an intervention using data-driven participatory processes to understand facility-level bottlenecks to optimise PMTCT implementation and to scale up priority PMTCT actions nationally. RESULTS. There was remarkable improvement across all key indicators in the PMTCT cascade over the 3 years 2011 - 2013. Simple monitoring tools such as a visual dashboard and data for action reports were successfully used to improve the performance of the PMTCT programme across SA. MTCT has shown a significant downward trend. CONCLUSIONS. It is feasible to implement district-level, data-driven quality improvement processes at a national scale to improve the performance of the PMTCT programme at the local level.http://www.samj.org.zaam201

Eliminating HIV transmission through breast milk from women taking antiretroviral drugs

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