Maintaining human milk bank services throughout the COVID-19 pandemic: A global response.

If maternal milk is unavailable, the World Health Organization recommends that the first alternative should be pasteurised donor human milk (DHM). Human milk banks (HMBs) screen and recruit milk donors, and DHM principally feeds very low birth weight babies, reducing the risk of complications and supporting maternal breastfeeding where used alongside optimal lactation support. The COVID-19 pandemic has presented a range of challenges to HMBs worldwide. This study aimed to understand the impacts of the pandemic on HMB services and develop initial guidance regarding risk limitation. A Virtual Collaborative Network (VCN) comprising over 80 HMB leaders from 36 countries was formed in March 2020 and included academics and nongovernmental organisations. Individual milk banks, national networks and regional associations submitted data regarding the number of HMBs, volume of DHM produced and number of recipients in each global region. Estimates were calculated in the context of missing or incomplete data. Through open-ended questioning, the experiences of milk banks from each country in the first 2 months of the pandemic were collected and major themes identified. According to data collected from 446 individual HMBs, more than 800,000 infants receive DHM worldwide each year. Seven pandemic-related specific vulnerabilities to service provision were identified, including sufficient donors, prescreening disruption, DHM availability, logistics, communication, safe handling and contingency planning, which were highly context-dependent. The VCN now plans a formal consensus approach to the optimal response of HMBs to new pathogens using crowdsourced data, enabling the benchmarking of future strategies to support DHM access and neonatal health in future emergencies.

Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases ß-Diversity in the Gut Microbiome of Human Immunodeficiency Virus-Exposed, Uninfected Infants.

BACKGROUND: Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined. METHODS: We analyzed whole-metagenome sequencing data from 163 longitudinally collected stool samples from 63 HEU infants randomized to receive (n = 34; CTX-T) or to not receive (n = 29; CTX-N) prophylactic cotrimoxazole treatment. We generated taxonomic, functional pathway, and resistance gene profiles for each sample and compared microbiome signatures between the CTX-T and CTX-N infants. RESULTS: Metagenomic analysis did not reveal significant differences in taxonomic or functional pathway α-diversity between CTX-T and CTX-N infants. In contrast, resistance gene prevalence (P = .00719) and α-diversity (P = .0045) increased in CTX-T infants. These differences increased over time for both resistance gene prevalence measured by log-normalized abundance (4-month mean, 0.71 [95% confidence interval {CI}, .2-1.2] and 6-month mean, 0.85 [95% CI, .1-1.7]) and α-diversity (P = .0045). Unlike α-diversity, interindividual gut microbiome taxonomic (mean, -0.11 [95% CI, -.15 to -.077]), functional taxonomic (mean, -0.050 [95% CI, -.084 to -.017]), and resistance gene (mean, -0.13 [95% CI, -.17 to -.099]) ß-diversity decreased in CTX-T infants compared with CTX-N infants. These results are consistent with persistent antibiotic selection pressure. CONCLUSIONS: Cotrimoxazole prophylaxis in HEU infants decreased gut microbiome ß-diversity and increased antibiotic resistance gene α-diversity and prevalence. Antibiotic resistance is a growing threat, especially in low- and middle-income countries where the higher perinatal HIV exposure rates result in cotrimoxazole prophylaxis. Understanding effects from current HEU infant antibiotic prophylaxis guidelines will inform guideline revisions and efforts to reduce increasing antibiotic resistance.

Point-of-care HIV testing best practice for early infant diagnosis: an implementation study.

BACKGROUND: With Universal Health Coverage and Integrated People-centred Health Care, streamlined health-systems and respectful care are necessary. South Africa has made great strides in prevention of mother-to-child transmission (PMTCT) but with the great burden of HIV, a minimum of birth and 10-week HIV-PCR testing are required for the estimated 360,000 HIV-exposed infants born annually which presents many challenges including delayed results and loss to follow-up. Point-of-care (POC) HIV testing of infants addresses these challenges well and facilitates initiation of HIV-infected infants rapidly after diagnosis for best clinical outcomes. METHODS: Objectives were to determine accuracy, feasibility and acceptability of POC testing compared to standard-of-care (SOC) central-laboratory testing. HIV-exposed infants for birth PCR testing in hospital (n = 323) and follow-up at a primary health care clinic (n = 117) in Durban, South Africa were included. A baseline situational-analysis reviewed registers and phoned mothers of HIV-exposed infants prior to the intervention. An effectiveness-implementation study of the Alere™q HIV-1/2 Detect POC test (heel-prick specimen processed in 50 min) was compared with SOC with questionnaires to mothers and staff. Stata 14 was used for analysis. RESULTS: At baseline 2% of birth HIV tests were missed; only 40% of mothers could be contacted; 17% did not receive birth test result; 19% did not have a 10-week test; 39% had not received the 10-week results. There were 5(1.5%) HIV-infected and 318(98.5%) HIV-negative infants detected in hospital with all clinic babies negative. All positive infants commenced ART before discharge. Ultimately POC and SOC had perfect concordance but for 10 SOC tests researchers actively tracked-down results or repeated tests. Turn around times for SOC tests were on average 8-days (IQR 6-10 days) and for POC testing was 0-days. The POC error-rate was 9,6% with all giving a result when repeated. The majority of mothers (92%) preferred POC testing with 7% having no preference. No staff preferred SOC testing with 79% preferring POC and 21% having no preference. CONCLUSIONS: Point-of-care HIV testing for EID is accurate, feasible and acceptable, with benefits of early ART for all positive infants at birth facilities. We recommend that it be considered best practice for EID. TRIAL REGISTRATION: ISRCTN38911104 registered 9 January 2018 - retrospectively registered.

A qualitative study exploring infant feeding decision-making between birth and 6 months among HIV-positive mothers.

Despite efforts to support breastfeeding for HIV-positive mothers in South Africa, being HIV-positive remains a barrier to initiating and sustaining breastfeeding. The aim was to explore decision-making about infant feeding practices among HIV-positive mothers in a rural and urban settings in KwaZulu-Natal, South Africa. HIV-positive pregnant women were purposively sampled from one antenatal clinic in each setting. A qualitative longitudinal cohort design was employed, with monthly in-depth interviews conducted over 6 months postdelivery. Data were analysed using framework analysis. We report findings from 11 HIV-positive women within a larger cohort. Participants were aged between 15 and 41 years and were all on antiretroviral therapy. Before delivery, nine mothers intended to exclusively breastfeed (EBF) for 6 months, and two intended to exclusively formula feed (EFF). Three mothers successfully EBF for 6 months, whereas four had stopped breastfeeding, and two were mixed breastfeeding by 6 months. Mothers reported receiving strong advice from health workers (HWs) to EBF and made decisions based primarily on HWs advice, resisting contrary pressure from family or friends. The main motivation for EBF was to protect the child from HIV acquisition, but sometimes fear of mixed feeding led to mothers stopping breastfeeding entirely. Infant feeding messages from HWs advice were frequently inadequate and out of date, and failed to address mothers' challenges. Minimal support was provided for EFF. In conclusion, HWs play a pivotal role in providing infant feeding support to HIV infected mothers, but need regular updates to ensure if advice is correct and appropriate.

Viraemia before, during and after pregnancy in HIV-infected women on antiretroviral therapy in rural KwaZulu-Natal, South Africa, 2010-2015.

OBJECTIVES: Pregnancy and post-partum viral load suppression is critical to prevent mother-to-child HIV transmission and ensure maternal health. We measured viraemia risk before, during and after pregnancy in HIV-infected women. METHODS: Between 2010 and 2015, 1425 HIV-infected pregnant women on lifelong antiretroviral therapy (ART) for at least six months pre-pregnancy were enrolled in a cohort study in rural KwaZulu-Natal, South Africa. Odds ratios were estimated in multilevel logistic regression, with pregnancy period time-varying. RESULTS: Over half of 1425 women received tenofovir-based regimens (n = 791). Median pre-pregnancy ART duration was 2.1 years. Of 988 women (69.3%) with pre-pregnancy viral loads, 82.0%, 6.8% and 11.2% had VL <50, 50-999 and ≥1000 copies/ml, respectively. During pregnancy and at six, 12 and 24 months, viral load was ≥1000 copies/ml in 15.2%, 15.7%, 17.8% and 16.6% respectively; viral load <50 was 76.9%, 77%, 75.5% and 75.8%, respectively. Adjusting for age, clinical and pregnancy factors, viraemia risk (viral load ≥50 copies/ml) was not significantly associated with pregnancy [adjusted OR (aOR) 1.31; 95% CI 0.90-1.92], six months (aOR 1.30; 95% CI 0.83-2.04), 12 months (aOR 0.96; 95% CI 0.58-1.58) and 24 months (aOR 1.40; 95% CI 0.89-2.22) post-partum. Adjusting for ART duration-pregnancy period interaction, viraemia risk was 1.8 during pregnancy and twofold higher post-partum. CONCLUSIONS: While undetectable viral load before pregnancy through post-partum was common, the UNAIDS goal to suppress viraemia in 90% of women was not met. Women on preconception ART remain vulnerable to viraemia; additional support is required to prevent mother-to-child HIV transmission and maintain maternal health.

A Cluster Randomised Trial to Determine the Efficacy of the "Feeding Buddies" Programme in Improving Exclusive Breastfeeding Rates Among HIV-Infected Women in Rural KwaZulu-Natal, South Africa.

This cluster randomised trial in KwaZulu-Natal South Africa, evaluated the implementation of a Feeding Buddies (FB) programme to improve exclusive breastfeeding (EBF) amongst human immunodeficiency virus infected mothers. Eight clinics were randomly allocated to intervention and control arms respectively. Pregnant women attending the prevention of mother-to-child transmission program and intending to EBF were enrolled: control (n = 326), intervention (n = 299). Intervention mothers selected FBs to support them and they were trained together (four sessions). Interviews of mothers occurred prenatally and at post-natal visits (day 3, weeks 6, 14 and 22). Breastfeeding results were analysed (Stata) as interval-censored time-to-event data, with up to four time intervals per mother. EBF rates at the final interview were similar for control and intervention groups: 44.68% (105/235) and 42.75% (109/255) respectively (p = 0.67). In Cox regression analysis better EBF rates were observed in mothers who received the appropriate training (p = 0.036), had a community care giver visit (p = 0.044), while controlling for other factors. Implementation realities reduced the potential effectiveness of the FBs.

Autonomy and infant feeding decision-making among teenage mothers in a rural and urban setting in KwaZulu-Natal, South Africa.

BACKGROUND: The nutritional status of infants born to teenage mothers can be sub-optimal compared to those born to older mothers. One contributing factor is inappropriate feeding practices adopted by teenage mothers. Little is known about how infant feeding decisions are made among teenage mothers, particularly in under resourced settings. In this study we prospectively explored autonomy and infant feeding decision-making among teenage mothers in a rural and urban setting in KwaZulu-Natal, South Africa. METHODS: This study adopted a qualitative longitudinal design. Thirty pregnant participants were recruited to the study cohort, from the catchment area of two hospitals (one urban and one rural). Participants were purposively selected to include teenagers, HIV positive, and working pregnant women. We report findings from ten teenage mothers, aged between 15 and 19 years, who participated in the larger cohort (n = 5 rural; n = 5 urban). Monthly in-depth interviews were conducted with participating mothers for 6 months starting 2 weeks after delivery. All interviews were conducted in the local language, transcribed verbatim and translated into English. Data was coded using NVivo v10 and framework analysis was used. RESULTS: Findings from this study showed that teenage mothers had knowledge about recommended feeding practices. However, our findings suggest that these mothers were not involved in infant feeding decisions once they were at home, because infant feeding decision-making was a role largely assumed by older mothers in the family. Further, the age of the mother and financial dependency diminished her autonomy and ability to influence feeding practices or challenge incorrect advice given at home. Most feeding advice shared by family members was inappropriate, leading to poor infant feeding practices among teenage mothers. Returning to school and fear of breastfeeding in public were also barriers to exclusive breastfeeding. CONCLUSION: Teenage mothers had a limited role in the infant feeding decision-making process. Health workers have an important role to play in ensuring that knowledge about infant feeding is shared with the mother's family where infant feeding choices are made. This will improve support for teenage mothers, and may also positively impact on the nutritional status of children.

Incident HIV during pregnancy and early postpartum period: a population-based cohort study in a rural area in KwaZulu-Natal, South Africa.

BACKGROUND: The evidence on the effect of pregnancy on acquiring HIV is conflicting, with studies reporting both higher and lower HIV acquisition risk during pregnancy when prolonged antiretroviral therapy was accessible. The aim of this study was to assess the pregnancy effect on HIV acquisition where antiretroviral therapy was widely available in a high HIV prevalence setting. METHODS: This is a retrospective cohort study nested within a population-based surveillance to determine HIV incidence in HIV-uninfected women from 15 to 49 years from 2010 through 2015 in rural KwaZulu-Natal. HIV incidence per 100 person-years according to pregnancy status (not pregnant, pregnant, to eight weeks postpartum) were measured in 5260 HIV-uninfected women. Hazard ratios (HR) were estimated by Cox proportional hazards regression with pregnancy included as a time varying variable. RESULTS: Overall, pregnancy HIV incidence was 4.5 per 100 person-years (95% CI 3.4-5.8), higher than non-pregnancy (4.0; 95% CI 3.7-4.3) and postpartum incidences (4.2 per 100 person-years; 95% CI 2.3-7.6). However, adjusting for age, and demographic factors, pregnant women had a lower risk of acquiring HIV (HR 0.4; 95% CI 0.2-0.9, P = 0.032) than non-pregnant women; there were no differences between postpartum and non-pregnant women (HR 1.2; 95% CI 0.4-3.2; P = 0.744). In models adjusting for the interaction of age and gravidity, pregnant women under 25 years with two or more pregnancies had a 2.3 times greater risk of acquiring HIV than their older counterparts (95% CI 1.3-4.3; P = 0.008). CONCLUSIONS: Pregnancy had a protective effect on HIV acquisition. Elevated HIV incidence in younger women appeared to be driven by those with higher gravidity. The sexual and biological factors in younger women should be explored further in order to design appropriate HIV prevention interventions.

Association of 6 months of exclusive breastfeeding with higher fat-free mass in infants in a low-resource setting with high HIV prevalence in South Africa.

Exclusive breastfeeding for 6 months is recommended by the World Health Organisation (WHO) for optimal health and growth of infants, but it is not a common practice in South Africa. A breastfeeding counselling programme was run to inform, encourage and support mothers to exclusively breastfeed their infants for 6 months, and mother-infant pairs were invited to participate in a research project to determine breast milk intake volumes using the dose-to-mother deuterium dilution stable isotope technique. This technique yields objective measurements of breast milk intake volumes and also enables determination of exclusivity of breastfeeding, which is most frequently determined by maternal recall and can be subject to bias. Exclusivity of breastfeeding at 6 weeks, 3 months and 6 months following birth of the infants was correlated with infant fat-free mass at 12 months, which was determined by the dose-to-infant deuterium dilution stable isotope technique. Results showed that infants who were exclusively breastfed for 6 months had a higher per cent fat-free mass at 12 months compared with infants who were not exclusively breastfed for 6 months (P < 0.05). This objective determination of both breastfeeding patterns and infant body composition gives weight to the WHO recommendation of exclusive breastfeeding for 6 months as it demonstrated adequate fat-free mass in infants at 12 months, even in an area with high HIV prevalence. © 2016 John Wiley & Sons Ltd.

Exclusive Breastfeeding and Cognition, Executive Function, and Behavioural Disorders in Primary School-Aged Children in Rural South Africa: A Cohort Analysis.

BACKGROUND: Exclusive breastfeeding (EBF) is associated with early child health; its longer-term benefits for child development remain inconclusive. We examine the associations between EBF, HIV exposure, and other maternal/child factors and the cognitive and emotional-behavioural development of children aged 7-11 y. METHODS AND FINDINGS: The Vertical Transmission Study (VTS) supported EBF in HIV-positive and HIV-negative women; between 2012 and 2014, HIV-negative VTS children (332 HIV exposed, 574 HIV unexposed) were assessed in terms of cognition (Kaufman Assessment Battery for Children Second Edition [KABC-II]), executive function (Developmental Neuropsychological Assessment Second Edition [NEPSY-II]), and emotional-behavioural functioning (parent-reported Child Behaviour Checklist, [CBCL]). We developed population means by combining the VTS sample with 629 same-aged HIV-negative children from the local demographic platform. For each outcome, we split the VTS sample into scores above or at/below each population mean and modelled each outcome using logistic regression analyses, overall and stratified by child sex. There was no demonstrated effect of EBF on overall cognitive functioning. EBF was associated with fewer conduct disorders overall (adjusted odds ratio [aOR] 0.44 [95% CI 0.3-0.7], p ≤ 0.01), and there was weak evidence of better cognition in boys who had been exclusively breastfed for 2-5 mo versus ≤1 mo (Learning subscale aOR 2.07 [95% CI 1.0-4.3], p = 0.05). Other factors associated with better child cognition were higher maternal cognitive ability (aOR 1.43 [95% CI 1.1-1.9], p = 0.02, Sequential; aOR 1.74 [95% CI 1.3-2.4], p < 0.001, Planning subscales) and crèche attendance (aOR 1.96 [95% CI 1.1-3.5], p = 0.02, Sequential subscale). Factors positively associated with executive function were home stimulation (aOR 1.36 [95% CI 1.0-1.8], p = 0.04, Auditory Attention; aOR 1.35 [95% CI 1.0-1.8], p = 0.05, Response Set) and crèche (aOR 1.74 [95% CI 1.0-3.0], p = 0.05, Animal Sorting). Maternal mental health problems and parenting stress were associated with increased emotional-behavioural problems on the total CBCL (aOR 2.44 [95% CI 1.3-4.6], p = 0.01; aOR 7.04 [95% CI 4.2-11.9], p < 0.001, respectively). Maternal HIV status was not associated with any outcomes in the overall cohort. Limitations include the nonrandomised study design and lack of maternal mental health assessment at the child's birth. CONCLUSIONS: EBF was associated with fewer than average conduct disorders and weakly associated with improved cognitive development in boys. Efforts to improve stimulation at home, reduce maternal stress, and enable crèche attendance are likely to improve executive function and emotional-behavioural development of children.

Postpasteurization Testing of Human Milk Sterility at Human Milk Banks in Resource-Limited Settings: An Alternative to Standard Microbiological Quality Testing.

Introduction: Pasteurized donor human milk provides nutrition and bioactive factors for infant growth and health when a mother's own milk is not available. Bacteriological testing is recommended for each pasteurized batch of donor milk before distribution to ensure that the milk is safe for use. Charm Peel Plates (CPPs) are a simplified, easy-to-use culture method for detecting microorganisms in milk and milk products. This study investigates the feasibility of using CPPs as an alternative test for current standard postpasteurization screening by human milk banks (HMBs), particularly those in resource-limited settings. Aim: The aim of this study was to evaluate the feasibility of using the CPP versus the 5% horse blood agar (HBA) plate (standard South African National Health Laboratory Service method) for detecting bacterial growth in pasteurized human milk samples. Methods: For each of the 50 pasteurized donor milk samples, 100-µL aliquots were cultured on routine HBA and 1 mL on CPPs for the total bacterial colony count. Any positive growth was identified using VITEK® 2 (bioMérieux). To demonstrate the ability of CPPs to support bacterial growth, four spiked samples were tested. Results: Concurrent negative test results were reported for 49/50 (98%) samples with only one positive test with HBA. Conclusions and Recommendations: The CPP is equivalent to HBA for detection of bacterial growth. Additional advantages of CPPs are ease of use and cost-effectiveness. The CPP is therefore recommended as a point-of-care, bacteriological screening method for donor human milk by HMBs, particularly those in resource-limited settings.

Breastfeeding in HIV exposed infants significantly improves child health: a prospective study.

Breastfeeding has been shown to benefit both maternal and child immune status. The impact of exclusive breastfeeding in the presence of HIV infection on maternal and child health is still unclear. Socio-economic factors make breast-feeding an important source of nutrition for an infant 6 months and under in the developing world. A prospective study was conducted to examine the impact of feeding mode on various maternal indices including anthropometry; body composition indicators (using FTIR); haematology and biochemical markers; as well as incidence rates of opportunistic infections and clinical disease progression. In infants we examined the impact on growth, development and morbidity. AFASS criteria (affordable, feasible, accessible, sustainable and safe) were fulfilled by 38.7% of the formula feeding mothers. No significant differences between the formula feeding and breastfeeding groups in terms of haematological, immunological and body composition changes were seen. Breastfeeding mothers had significantly lower events with high depression scores (P = 0.043). Breastfeeding infants had a significantly lower risk of diarrhoea and hospitalisation at 3 months (P = 0.006 and 0.014 respectively). Breastfeeding was significantly associated with better development scores and growth parameters. Breastfeeding is not harmful to the mother in the presence of HIV infection. Mothers are still choosing formula feeding inappropriately despite counselling about the AFASS criteria. Breastfeeding is beneficial to the infants especially in the first 3 months of life.

Getting to under 1% vertical HIV transmission: lessons from a breastfeeding cohort in South Africa.

We report here on the transmission of HIV in a cohort of breastfeeding infants enrolled in a prevention of mother to child HIV transmission (PMTCT) programme at the epicentre of the HIV pandemic. South Africa implemented option B+ for PMTCT in 2015. Between 2013 and 2018, we enrolled 1219 infants born to HIV positive women into a non-inferiority trial assessing the current cotrimoxazole prophylaxis guidelines for HIV-exposed uninfected infants. Breastfeeding mothers and infants were enrolled and followed up at one of two clinics in eThekwini, KwaZulu-Natal, until 12 months of age. During the study period, 8 infants seroconverted (<1% transmission); these were likely four birth transmissions and four breastfeeding transmissions. It is critical in the post option B era to assess the reasons for vertical transmission of HIV to enable healthcare workers and policy makers to provide strategies to mitigate future infections. This report details the possible contributors to vertical transmission in this cohort and highlights the continued strategies that should be employed to further our goal towards reaching the elimination of mother to child HIV transmission.

Cotrimoxazole guidelines for infants who are HIV-exposed but uninfected: a call for a public health and ethics approach to the evidence.

WHO first recommended cotrimoxazole prophylaxis for all infants who are HIV-exposed but uninfected (HEU) in 2000, given the ability of this treatment to prevent mortality from pneumocystis pneumonia in adults living with HIV. Over the last 21 years, evidence has been generated from the use of cotrimoxazole prophylaxis in infants who are HEU, including two randomised controlled trials, which have shown no clinical benefit and an increase in antibiotic resistance and microbiome dysbiosis. Additionally, improvements in health care over the last two decades in terms of antiretroviral treatment and prophylaxis for mothers and infants, and notably improved vaccination programmes, have substantially reduced the risk of HIV transmission and the overall morbidity and mortality of infants who are HEU from pneumonia and diarrhoeal diseases. Here, we highlight these changes in health care alongside the unchanged cotrimoxazole prophylaxis guidelines and call for a change in these guidelines on the basis of a public health and ethics approach.

Point-of-care CD4 testing: Differentiated care for the most vulnerable.

BACKGROUND: South Africa, with the highest burden of HIV infection globally, has made huge strides in its HIV/ART programme, but AIDS deaths have not decreased proportionally to ART uptake. Advanced HIV disease (CD4 < 200 cells/mm3) persists, and CD4 count testing is being overlooked since universal test-and-treat was implemented. Point-of-care CD4 testing could address this gap and assure differentiated care to these vulnerable patients with low CD4 counts. METHODS: A time randomised implementation trial was conducted, enrolling 603 HIV positive non-ART, not pregnant patients at a primary health care clinic in Durban, South Africa. Weeks were randomised to either point-of-care CD4 testing (n = 305 patients) or standard-of-care central laboratory CD4 testing (n = 298 patients) to assess the proportion initiating ART at 3 months. Cox regression, with robust standard errors adjusting for clustering by week, were used to assess the relationship between treatment initiation and arm. RESULTS: Among the 578 (299 point-of-care and 279 standard-of-care) patients eligible for analysis, there was no significant difference in the number of eligible patients initiating ART within 3 months in the point-of-care (73%) and the standard-of-care (68%) groups (P = 0.112). The time-to-treat analysis was not significantly different in patients with CD4 counts of 201-500 cells/mm3 which could have been due to appointment scheduling to cope with the large burden of cases. However, in patients with advanced HIV disease (CD4 < 200cells/mm3) 65% more patients started ART earlier in the point-of-care group (HR 1.65 (95% confidence interval (CI) = 0.99-2.75; P = 0.052) compared to the standard-of-care group. CONCLUSIONS: Point-of-care testing decreased time-to-treatment in those with advanced HIV disease. With universal test and treat for HIV, rollout of simple point-of-care CD4 testing would ensure early diagnosis of advanced HIV disease and facilitate differentiated care for these vulnerable patients as per the World Health Organisation 2020 target product profile for point-of-care CD4 testing. TRIAL REGISTRATION: ISRCTN14220457.

Cumulative exposure to cell-free HIV in breast milk, rather than feeding pattern per se, identifies postnatally infected infants.

BACKGROUND: We quantified the relationship between human immunodeficiency virus (HIV) RNA shedding in breast milk, cumulative RNA exposure, and postnatal transmission, relating timing of infection in the infant to estimated total volume of milk exposure. METHODS: Nested case-control study of 36 infants of HIV-infected mothers. Case patients were infants who acquired HIV infection through breastfeeding from age 6 through 28 weeks, and control subjects were uninfected infants matched on age at obtainment of a breast milk sample. Mothers and infants received peripartum single-dose nevirapine prophylaxis. Feeding data were collected daily; breast milk samples were collected and infant anthropometry was performed at 6 weeks and monthly thereafter. Volume of milk ingested was estimated using infant weight and feeding pattern. RESULTS: Before HIV acquisition in case patients, feeding pattern (exclusive breastfeeding; median duration, 65 vs 70 days; P = .6) and daily milk intake (mean volume, 638 vs 637 mL; P = .97) did not differ significantly between case patients and control subjects. Case mothers were more likely to shed virus (64% vs 9% always, 22% vs 20.5% intermittently, 14% vs 70.5% never shed; overall, P < .001). Case patients ingested ~15 times more HIV-1 RNA particles than did control subjects (196.5 vs 13 × 106 copies; P < .001). Allowing for maternal antenatal CD4 cell count and plasma HIV-1 load, child sex and duration of mixed breastfeeding, the association between HIV RNA exposure and infection remained statistically significant (P < .001). CONCLUSIONS: Postnatal acquisition of HIV-1 is more strongly associated with cumulative exposure to cell-free particles in breast milk than with feeding mode. Reducing breast milk viral load through antiretroviral therapy to mother or child can further decrease postnatal transmission in exclusively breastfed infants.