Acceptability and utilisation of voluntary HIV testing and nevirapine to reduce mother-to-child transmission of HIV-1 integrated into routine clinical care.

OBJECTIVES: Use of nevirapine for prevention of mother-to-child transmission (PMTCT) of HIV-1 has been routine clinical care at Coronation Women and Children's Hospital since April 2000. We assessed the effect of regular audit and targeted interventions on the utilisation of the PMTCT programme. METHODS: Review of antenatal cards and hospital records of women discharged following delivery, in three time periods between October 2000 and February 2002. Following the initial audit an intervention was implemented to eliminate weaknesses in our PMTCT service. Following the second audit the hospital became a pilot site for the Gauteng PMTCT programme. RESULTS: In the initial audit 53.2% of women (159/299) were tested for HIV and received their results, while 56% (14/25) of identified HIV-infected women, and 16% (4/25) of their infants, received nevirapine. By the third audit 74.3% of women (266/358) received their results, and 86% (43/50) of HIV-positive women and 74% (37/50) of newborns were documented to have received nevirapine. In all three audits over 90% of women initiating antenatal care at the hospital were tested for HIV, while women who initiated care at district community clinics were less likely to receive testing. CONCLUSIONS: Ongoing audit has been important for targeting obstacles to detection of HIV-infected women and documented nevirapine uptake by women and infants. Rates of HIV testing and nevirapine use have increased significantly. Voluntary counselling and testing for HIV and use of nevirapine are acceptable to pregnant women in our setting. Roll-out of the pilot programme to district community clinics is essential for further improvement.     

Timing of HIV testing among pregnant and breastfeeding women and risk of mother‐to‐child HIV transmission in Malawi: a sampling‐based cohort study

IntroductionPregnant women living with HIV can achieve viral suppression and prevent HIV mother‐to‐child transmission (MTCT) with timely HIV testing and early ART initiation and maintenance. Although it is recommended that pregnant women undergo HIV testing early in antenatal care in Malawi, many women test positive during breastfeeding because they did not have their HIV status ascertained during pregnancy, or they tested negative during pregnancy but seroconverted postpartum. We sought to estimate the association between the timing of last positive HIV test (during pregnancy vs. breastfeeding) and outcomes of maternal viral suppression and MTCT in Malawi’s PMTCT programme.MethodsWe conducted a two‐stage cohort study among mother–infant pairs in 30 randomly selected high‐volume health facilities across five nationally representative districts of Malawi between 1 July 2016 and 30 June 2017. Log‐binomial regression was used to estimate prevalence ratios (PR) and risk ratios (RR) for associations between timing of last positive HIV test (i.e. breastfeeding vs. pregnancy) and maternal viral suppression and MTCT, controlling for confounding using inverse probability weighting.ResultsOf 822 mother–infant pairs who had available information on the timing of the last positive HIV test, 102 mothers (12.4%) had their last positive test during breastfeeding. Women who lived one to two hours (PR = 2.15; 95% CI: 1.29 to 3.58) or >2 hours (PR = 2.36; 95% CI: 1.37 to 4.10) travel time to the nearest health facility were more likely to have had their last positive HIV test during breastfeeding compared to women living <1 hour travel time to the nearest health facility. The risk of unsuppressed VL did not differ between women who had their last positive HIV test during breastfeeding versus pregnancy (adjusted RR [aRR] = 0.87; 95% CI: 0.48 to 1.57). MTCT risk was higher among women who had their last positive HIV test during breastfeeding compared to women who had it during pregnancy (aRR = 6.57; 95% CI: 3.37 to 12.81).ConclusionsMTCT in Malawi occurred disproportionately among women with a last positive HIV test during breastfeeding. Testing delayed until the postpartum period may lead to higher MTCT. To optimize maternal and child health outcomes, PMTCT programmes should focus on early ART initiation and providing targeted testing, prevention, treatment and support to breastfeeding women.     

Efficacy of WHO recommendation for continued breastfeeding and maternal cART for prevention of perinatal and postnatal HIV transmission in Zambia

Introduction

To prevent mother-to-child transmission (MTCT) of HIV in developing countries, new World Health Organization (WHO) guidelines recommend maternal combination antiretroviral therapy (cART) during pregnancy, throughout breastfeeding for 1 year and then cessation of breastfeeding (COB). The efficacy of this approach during the first six months of exclusive breastfeeding has been demonstrated, but the efficacy of this approach beyond six months is not well documented.

Methods

A prospective observational cohort study of 279 HIV-positive mothers was started on zidovudine/3TC and lopinavir/ritonavir tablets between 14 and 30 weeks gestation and continued indefinitely thereafter. Women were encouraged to exclusively breastfeed for six months, complementary feed for the next six months and then cease breastfeeding between 12 and 13 months. Infants were followed for transmission to 18 months and for survival to 24 months. Text message reminders and stipends for food and transport were utilized to encourage adherence and follow-up.

Results

Total MTCT was 9 of 219 live born infants (4.1%; confidence interval (CI) 2.2–7.6%). All breastfeeding transmissions that could be timed (5/5) occurred after six months of age. All mothers who transmitted after six months had a six-month plasma viral load >1,000 copies/ml (p<0.001). Poor adherence to cART as noted by missed dispensary visits was associated with transmission (p=0.04). Infant mortality was lower after six months of age than during the first six months of life (p=0.02). The cumulative rate of infant HIV infection or death at 18 months was 29/226 (12.8% 95 CI: 7.5–20.8%).

Conclusions

Maternal cART may limit MTCT of HIV to the UNAIDS target of <5% for eradication of paediatric HIV within the context of a clinical study, but poor adherence to cART and follow-up can limit the benefit. Continued breastfeeding can prevent the rise in infant mortality after six months seen in previous studies, which encouraged early COB.     

Plasma viraemia in HIV-positive pregnant women entering antenatal care in South Africa

Introduction

Plasma HIV viral load (VL) is the principle determinant of mother-to-child HIV transmission (MTCT), yet there are few data on VL in populations of pregnant women in sub-Saharan Africa. We examined the distribution and determinants of VL in HIV-positive women seeking antenatal care (ANC) in Cape Town, South Africa.

Methods

Consecutive HIV-positive pregnant women making their first antenatal clinic visit were recruited into a cross-sectional study of viraemia in pregnancy, including a brief questionnaire and specimens for VL testing and CD4 cell enumeration.

Results & discussion

Overall 5551 pregnant women sought ANC during the study period, of whom 1839 (33%) were HIV positive and 1521 (85%) were included. Approximately two-thirds of HIV-positive women in the sample (n=947) were not on antiretrovirals at the time of the first ANC visit, and the remainder (38%, n=574) had initiated antiretroviral therapy (ART) prior to conception. For women not on ART, the median VL was 3.98 log₁₀ copies/mL; in this group, the sensitivity of CD4 cell counts ≤350 cells/µL in detecting VL>10,000 copies/mL was 64% and this increased to 78% with a CD4 threshold of ≤500 cells/µL. Among women on ART, 78% had VL<50 copies/mL and 13% had VL >1000 copies/mL at the time of their ANC visit.

Conclusions

VL >10,000 copies/mL was commonly observed in women not on ART with CD4 cell counts >350 cells/µL, suggesting that CD4 cell counts may not be adequately sensitive in identifying women at greatest risk of MTCT. A large proportion of women entering ANC initiated ART before conception, and in this group more than 10% had VL>1000 copies/mL despite ART use. VL monitoring during pregnancy may help to identify pregnancies that require additional clinical attention to minimize MTCT risk and improve maternal and child health outcomes.     

Multivitamin supplementation improves haematologic status in children born to HIV-positive women in Tanzania

Introduction

Anaemia is prevalent among children born to HIV-positive women, and it is associated with adverse effects on cognitive and motor development, growth, and increased risks of morbidity and mortality.

Objective

To examine the effect of daily multivitamin supplementation on haematologic status and mother-to-child transmission (MTCT) of HIV through breastfeeding.

Methods

A total of 2387 infants born to HIV-positive women from Dar es Salaam, Tanzania were enrolled in a randomized, double-blind, placebo-controlled trial, and provided a daily oral supplement of multivitamins (vitamin B complex, C and E) or placebo at age 6 weeks for 24 months. Among them, 2008 infants provided blood samples and had haemoglobin concentrations measured at baseline and during a follow-up period. Anaemia was defined as haemoglobin concentrations<11 g/dL and severe anaemia<8.5 g/dL.

Results

Haemoglobin concentrations among children in the treatment group were significantly higher than those in the placebo group at 12 (9.77 vs. 9.64 g/dL, p=0.03), 18 (9.76 vs. 9.57 g/dL, p=0.004), and 24 months (9.93 vs. 9.75 g/dL, p=0.02) of follow-up. Compared to those in the placebo group, children in the treatment group had a 12% lower risk of anaemia (hazard ratio (HR): 0.88; 95% CI: 0.79–0.99; p=0.03). The treatment was associated with a 28% reduced risk of severe anaemia among children born to women without anaemia (HR: 0.72; 95% CI: 0.56–0.92; p=0.008), but not among those born to women with anaemia (HR: 1.10; 95% CI: 0.79–1.54; p=0.57; p for interaction=0.007). One thousand seven hundred fifty three infants who tested HIV-negative at baseline and had HIV testing during follow-up were included in the analysis for MTCT of HIV. No association was found between multivitamin supplements and MTCT of HIV.

Conclusions

Multivitamin supplements improve haematologic status among children born to HIV-positive women. Further trials focusing on anaemia among HIV-exposed children are warranted in the context of antiretroviral therapy.     

HIV prevention is not enough: child survival in the context of prevention of mother to child HIV transmission

Clinical and epidemiologic research has identified increasingly effective interventions to reduce mother to child HIV transmission in resource‐limited settings These scientific breakthroughs have been implemented in some programmes, although much remains to be done to improve coverage and quality of these programmes. But prevention of HIV transmission is not enough. It is necessary also to consider ways to improve maternal health and protect child survival. A win‐win approach is to ensure that all pregnant and lactating women with CD4 counts of <350 cells/mm³ have access to antiretroviral therapy. On its own, this approach will substantially improve maternal health and markedly reduce mother to child HIV transmission during pregnancy and delivery and through breastfeeding. This approach can be combined with additional interventions for women with higher CD4 counts, either extended prophylaxis to infants or extended regimens of antiretroviral drugs to women, to reduce transmission even further. Attempts to encourage women to abstain from all breastfeeding or to shorten the optimal duration of breastfeeding have led to increases in mortality among both uninfected and infected children. A better approach is to support breastfeeding while strengthening programmes to provide antiretroviral therapy for pregnant and lactating women who need it and offering antiretroviral drug interventions through the duration of breastfeeding. This will lead to reduced HIV transmission and will protect the health of women without compromising the health and well‐being of infants and young children.     

Effect of a mother-to-child HIV prevention programme on infant feeding and caring practices in South Africa.

OBJECTIVES: To conduct a rapid assessment of the impact of the Khayelitsha Prevention of Mother-to-Child Transmission (MTCT) programme on infant care practices among programme participants and the local population. STUDY DESIGN: Cross-sectional survey and qualitative in-depth interviews. SETTING. Khayelitsha, a large formal and informal settlement of about 300,000 people on the outskirts of Cape Town. At the time of the study the HIV seroprevalence rate among antenatal women was about 15% and the MTCT programme had enrolled nearly 800 infected women. SUBJECTS: Seventy randomly selected caregivers with young children in the survey; in-depth structured interviews with 11 nutrition counsellors and 11 mothers enrolled in the programme. RESULTS: Caregivers have good knowledge of the spread and prevention of HIV. A majority knew that breast-feeding can transmit HIV but 90% stated that this did not affect their feeding decisions. Over 80% had stopped exclusively breast-feeding by the time their infants were 3 months of age. All of the respondents felt that being diagnosed HIV-positive would result in serious social and domestic consequences. None of the health workers could correctly estimate the risk of spreading HIV through breast-feeding and many reported feeling confused about what they should counsel mothers. All the mothers on the programme reported exclusive formula-feeding. Some had serious problems with preparation and feeding of formula milk. Nearly all reported running out of feeds before being able to fetch new supplies. None reported any negative social effects of not breast-feeding. Most of the mothers endorsed the programme and felt that it had given them strength to face up to and plan for the consequences of their diagnosis. CONCLUSION: This rapid appraisal of the infant feeding and care component of the MTCT programme has raised a number of important challenges which health managers and policymakers need to address. Similar assessments in the new pilot sites will be important.     

Optimizing HIV retesting during pregnancy and postpartum in four countries: a cost‐effectiveness analysis

IntroductionHIV retesting during late pregnancy and breastfeeding can help detect new maternal infections and prevent mother‐to‐child HIV transmission (MTCT), but the optimal timing and cost‐effectiveness of maternal retesting remain uncertain.MethodsWe constructed deterministic models to assess the health and economic impact of maternal HIV retesting on a hypothetical population of pregnant women, following initial testing in pregnancy, on MTCT in four countries: South Africa and Kenya (high/intermediate HIV prevalence), and Colombia and Ukraine (low HIV prevalence). We evaluated six scenarios with varying retesting frequencies from late in antenatal care (ANC) through nine months postpartum. We compared strategies using incremental cost‐effectiveness ratios (ICERs) over a 20‐year time horizon using country‐specific thresholds.ResultsWe found maternal retesting once in late ANC with catch‐up testing through six weeks postpartum was cost‐effective in Kenya (ICER = $166 per DALY averted) and South Africa (ICER=$289 per DALY averted). This strategy prevented 19% (Kenya) and 12% (South Africa) of infant HIV infections. Adding one or two additional retests postpartum provided smaller benefits (1 to 2 percentage point increase in infections averted versus one retest). Adding three retests during the postpartum period averted additional infections (1 to 3 percentage point increase in infections averted versus one retest) but ICERs ($7639 and in Kenya and $11 985 in South Africa) greatly exceeded the cost‐effectiveness thresholds. In Colombia and Ukraine, all retesting strategies exceeded the cost‐effectiveness threshold and prevented few infant infections (up to 31 and 5 infections, respectively).ConclusionsIn high HIV burden settings with MTCT rates similar to those seen in Kenya and South Africa, HIV retesting once in late ANC, with subsequent intervention, is the most cost‐effective strategy for preventing infant HIV infections. In these settings, two HIV retests postpartum marginally reduced MTCT and were less costly than adding three retests. Retesting in low‐burden settings with MTCT rates similar to Colombia and Ukraine was not cost‐effective at any time point due to very low HIV prevalence and limited breastfeeding.     

Uptake of early infant diagnosis in Thailand’s national program for preventing mother-to-child HIV transmission and linkage to care, 2008–2011

Introduction

Early infant diagnosis (EID) has been a component of Thailand''s prevention of mother-to-child HIV transmission (PMTCT) programme since 2007. This study assessed the uptake, EID coverage, proportion of HIV-exposed infants receiving a definitive HIV diagnosis, mother-to-child transmission (MTCT) rates and linkage to HIV care and treatment.

Methods

Infant polymerase chain reaction (PCR) testing data from the National AIDS Program database were analyzed. EID coverage was calculated as the percentage of number of HIV-exposed infants receiving ≥1 HIV PCR test divided by the number of HIV-exposed infants estimated from HIV prevalence and live-birth registry data. Definitive HIV diagnosis was defined as having two concordant PCR results. MTCT rates were calculated based on infants tested with PCR and applied as a best-case scenario, and a sensitivity analysis was used to adjust these rates in average and worst scenarios. We defined linkage to HIV care as infants with at least one PCR-positive test who were registered with Thailand''s National AIDS Program. Chi-squared tests for linear trend were used to analyze changes in programme coverage.

Results

For 2008 to 2011, the average EID coverage rate increased from 54 to 76% (p<0.001), with 65% coverage (13,761/21,099) overall. The number of hospitals submitting EID samples increased from 458 to 645, and the percentage of community hospitals submitting samples increased from 75 to 78% (p=0.044). A definitive HIV diagnosis was made for 10,854 (79%) infants during this period. The adjusted MTCT rates had significantly decreasing trends in all scenarios. Overall, an estimated 53% (429/804) of HIV-infected infants were identified through the EID programme, and 80% (341/429) of infants testing positive were linked to care. The overall rate of antiretroviral treatment (ART) initiation within one year of age was 37% (157/429), with an increasing trend from 28 to 52% (p<0.001).

Conclusions

EID coverage increased and MTCT rates decreased during 2008 to 2011; however, about half of HIV-infected infants still did not receive EID. Most HIV-infected infants were linked to care but less than half initiated ART within one year of age. Active follow-up of HIV-exposed infants to increase early detection of HIV infection and early initiation of ART should be more widely implemented.     

High HIV incidence in the postpartum period sustains vertical transmission in settings with generalized epidemics: a cohort study in Southern Mozambique

Introduction

Acute infection with HIV in the postpartum period results in a high risk of vertical transmission through breastfeeding. A study was done to determine the HIV incidence rate and associated risk factors among postpartum women in Southern Mozambique, where HIV prevalence among pregnant women is 21%.

Methods

A prospective cohort study was conducted in six rural health facilities in Gaza and Maputo provinces from March 2008 to July 2011. A total of 1221 women who were HIV-negative on testing at delivery or within two months postpartum were recruited and followed until 18 months postpartum. HIV testing, collection of dried blood spot samples and administration of a structured questionnaire to women were performed every three months. Infant testing by DNA-PCR was done as soon as possible after identification of a new infection in women. HIV incidence was estimated, and potential risk factors at baseline were compared using Poisson regression.

Results

Data from 957 women were analyzed with follow-up after the enrolment visit, with a median follow-up of 18.2 months. The HIV incidence in postpartum women is estimated at 3.20/100 women-years (95% CI: 2.30–4.46), with the highest rate among 18- to 19-year-olds (4.92 per 100 women-years; 95% CI: 2.65–9.15). Of the new infections, 14 (34%) were identified during the first six months postpartum, 11 (27%) between 6 and 12 months and 16 (39%) between 12 and 18 months postpartum. Risk factors for incident HIV infection include young age, low number of children, higher education level of the woman''s partner and having had sex with someone other than one''s partner. The vertical transmission was 21% (95% CI: 5–36) among newly infected women.

Conclusions

Incidence of HIV is high among breastfeeding women in Southern Mozambique, contributing to increasing numbers of HIV-infected infants. Comprehensive primary prevention strategies targeting women of reproductive age, particularly pregnant and postpartum women and their partners, will be crucial for the elimination of paediatric AIDS in Africa.     

24‐Month HIV‐free survival among HIV‐exposed Infants in Lesotho: the PEAWIL cohort study

IntroductionFollowing the implementation of the provision of lifelong antiretroviral therapy to all HIV‐positive pregnant or breastfeeding women for prevention of mother‐to‐child transmission (PMTCT) of HIV by the Kingdom of Lesotho in 2013, we assessed the effectiveness of this approach by evaluating 24‐month HIV‐free survival among HIV‐exposed infants (HEIs).MethodsWe conducted a prospective observational cohort study that enrolled HIV‐positive and HIV‐negative pregnant women, with follow‐up of women and their infants for 24 months after delivery. Participant recruitment started in June 2014 and follow‐up ended in September 2018. Trained nurses collected study information through patient interviews and chart abstraction at enrolment and every three to six months thereafter. Maternal HIV testing, infant mortality, HIV transmission and HIV‐free survival rates were computed using Kaplan–Meier estimation. Cox regression hazard models were used to identify factors associated with infant HIV infection and death.ResultsBetween June 2014 and February 2016, we enrolled 653 HIV‐positive and 941 HIV‐negative pregnant women. Twenty‐seven HIV‐negative women acquired HIV during follow‐up. Ultimately, 634 liveborn HEI (382 (52%) male, 303 (48%) female, 3 missing) and 839 who remained HIV‐unexposed (HUIs) (409 (49.0%) male, 426 (51.0%) female, 4 missing) were followed; 550 HEIs and 701 HUIs completed the 24‐month follow‐up period. Of 607 (95.7%) HEIs who were tested for HIV at least once during follow‐up, 17 were found to be HIV‐positive. Two (9.5%) of 21 infants born to mothers who acquired HIV infection during follow‐up were HIV‐positive compared to 15 (2.4%) of 613 HEI born to women with known HIV infection. The risk of HIV transmission from HIV‐positive mothers to their infants by 24 months of age was 2.9% (95% CI: 1.8 to 4.7). The estimated 24‐month mortality rate among HEIs was 6.0% (95% CI: 4.4 to 8.2) compared to 3.8% (95% CI: 2.6 to 5.3) among HUIs (Log‐rank p = 0.065). HIV‐free survival at 24 months was 91.8% (95% CI: 89.2 to 93.7). Lower maternal age and birth weight were independently associated with increased HIV infection or death of infants.ConclusionsThe implementation of lifelong ART for PMTCT in the Lesotho public health system resulted in low HIV transmission, but survival of HEI remains lower than their HIV uninfected counterparts.     

Optimal breastfeeding durations for HIV‐exposed infants: the impact of maternal ART use,infant mortality and replacement feeding risk

Introduction

In 2010, the WHO recommended women living with HIV breastfeed for 12 months while taking antiretroviral therapy (ART) to balance breastfeeding benefits against HIV transmission risks. To inform the 2016 WHO guidelines, we updated prior research on the impact of breastfeeding duration on HIV‐free infant survival (HFS) by incorporating maternal ART duration, infant/child mortality and mother‐to‐child transmission data.

Methods

Using the Cost‐Effectiveness of Preventing AIDS Complications (CEPAC)‐Infant model, we simulated the impact of breastfeeding duration on 24‐month HFS among HIV‐exposed, uninfected infants. We defined “optimal” breastfeeding durations as those maximizing 24‐month HFS. We varied maternal ART duration, mortality rates among breastfed infants/children, and relative risk of mortality associated with replacement feeding (“RRRF”), modelled as a multiplier on all‐cause mortality for replacement‐fed infants/children (range: 1 [no additional risk] to 6). The base‐case simulated RRRF = 3, median infant mortality, and 24‐month maternal ART duration.

Results

In the base‐case, HFS ranged from 83.1% (no breastfeeding) to 90.2% (12‐months breastfeeding). Optimal breastfeeding durations increased with higher RRRF values and longer maternal ART durations, but did not change substantially with variation in infant mortality rates. Optimal breastfeeding durations often exceeded the previous WHO recommendation of 12 months.

Conclusions

In settings with high RRRF and long maternal ART durations, HFS is maximized when mothers breastfeed longer than the previously‐recommended 12 months. In settings with low RRRF or short maternal ART durations, shorter breastfeeding durations optimize HFS. If mothers are supported to use ART for longer periods of time, it is possible to reduce transmission risks and gain the benefits of longer breastfeeding durations.

     

Tracing defaulters in HIV prevention of mother-to-child transmission programmes through community health workers: results from a rural setting in Zimbabwe

Introduction

High retention in care is paramount to reduce vertical human immunodeficiency virus (HIV) infections in prevention of mother-to-child transmission (PMTCT) programmes but remains low in many sub-Saharan African countries. We aimed to assess the effects of community health worker–based defaulter tracing (CHW-DT) on retention in care and mother-to-child HIV transmission, an innovative approach that has not been evaluated to date.

Methods

We analyzed patient records of 1878 HIV-positive pregnant women and their newborns in a rural PMTCT programme in the Tsholotsho district of Zimbabwe between 2010 and 2013 in a retrospective cohort study. Using binomial regression, we compared vertical HIV transmission rates at six weeks post-partum, and retention rates during the perinatal PMTCT period (at delivery, nevirapine [NVP] initiation at three days post-partum, cotrimoxazole (CTX) initiation at six weeks post-partum, and HIV testing at six weeks post-partum) before and after the introduction of CHW-DT in the project.

Results

Median maternal age was 27 years (inter-quartile range [IQR] 23 to 32) and median CD4 count was 394 cells/µL³ (IQR 257 to 563). The covariate-adjusted rate ratio (aRR) for perinatal HIV transmission was 0.72 (95% confidence intervals [95% CI] 0.27 to 1.96, p=0.504), comparing patient outcomes after and before the intervention. Among fully retained patients, 11 (1.9%) newborns tested HIV positive. ARRs for retention in care were 1.01 (95% CI 0.96 to 1.06, p=0.730) at delivery; 1.35 (95% CI 1.28 to 1.42, p<0.001) at NVP initiation; 1.78 (95% CI 1.58 to 2.01, p<0.001) at CTX initiation; and 2.54 (95% CI 2.20 to 2.93, p<0.001) at infant HIV testing. Cumulative retention after and before the intervention was 496 (85.7%) and 1083 (87.3%) until delivery; 480 (82.9%) and 1005 (81.0%) until NVP initiation; 303 (52.3%) and 517 (41.7%) until CTX initiation; 272 (47.0%) and 427 (34.4%) until infant HIV testing; and 172 (29.7%) and 405 (32.6%) until HIV test result collection.

Conclusions

The CHW-DT intervention did not reduce perinatal HIV transmission significantly. Retention improved moderately during the post-natal period, but cumulative retention decreased rapidly even after the intervention. We showed that transmission in resource-limited settings can be as low as in resource-rich countries if patients are fully retained in care. This requires structural changes to the regular PMTCT services, in which community health workers can, at best, play a complementary role.     

Targeted HIV testing at birth supported by low and predictable mother‐to‐child transmission risk in Botswana

Introduction

Most African countries perform infant HIV testing at 6 weeks or later. The addition of targeted testing at birth may improve retention in care, treatment outcomes and survival for HIV‐infected infants.

Methods

HIV‐exposed infants were screened as part of the Early Infant Treatment (EIT) study in Botswana. Screened infants were ≥35 weeks gestational age and ≥2000 g at birth. Risk factors for mother‐to‐child transmission (MTCT) were assessed by maternal obstetric card or verbally. Risk factors included <8 weeks ART in pregnancy, last known CD4 <250 cells/mm³, last known HIV RNA >400 copies/mL, poor maternal ART adherence, lack of maternal zidovudine (ZDV) in labour, or lack of infant post‐exposure prophylaxis. Infants underwent dried blood spot testing by Roche Cobas Ampliprep/Cobas Taqman HIV‐1 qualitative PCR.

Results

From April 2015 to April 2016, 2303 HIV‐exposed infants were tested for HIV in the EIT study. Of these, 369 (16%) were identified as high risk for HIV infection by information available at birth, and 12 (0.5% overall, 3.25% of high risk) were identified as HIV positive at birth. All 12 positive infants were identified as high risk at the time of screening, and only 2 risk factors were required to identify all positive infants: either <8 weeks of maternal ART in pregnancy (75%) or lack of maternal HIV suppression at last test (25%).

Conclusions

In utero MTCT occurred only among infants identified as high risk at delivery, using information available from the mother or obstetric record. Birth testing that targets high‐risk infants based on maternal ART receipt is likely to identify the majority of in utero HIV transmissions, and allows early ART initiation for these infants.

     

Determinants of HIV-1 mother-to-child transmission in Southern Brazil

Different human immunodeficiency virus type 1 (HIV-1) subtypes may have distinct biological, immunological and pathogenic properties. Efficiency of mother-to-child transmission (MTCT) may be among those properties, but few and controversial results have been described so far. In this study, 102 children born from HIV-1-infected mothers between 1998 and 2004 in the city of Rio Grande, Brazil were analyzed for potential risk factors associated with MTCT. That geographic region is characterized by a high proportion of subtype C-infected subjects, and it allowed comparison between subtypes B and C and their influence on MTCT. The analysis also included clinical, obstetric and immunological parameters. Multivariate regression analyses were conducted to evaluate the influence of the parameters on MTCT, and prevalence ratios (PR) and 95% confidence intervals (CI95) were also calculated. A surprisingly high prevalence of subtype C of over 70% was found. Only the HIV viral load and the use of ACTG 076 protocol were predictive of MTCT. HIV subtype and CD4 T-cell counts were not associated with increased risk of transmission. Although a clear expansion of subtype C is evident in southern Brazil, it does not seem to correlate with increased risk of vertical transmission.     

Clinical significance of serum levels of thyroid stimulating hormone receptor antibody in pregnant women with Graves′disease

<正>Objective:To investigate the clinical significance of serum thyroid stimulating hormone(TSH) receptor antibody (TRAb) levels and the antithyroid drug(ATDs) use in pregnant women with Graves' disease in their neonatal thyroid function. Methods:The serum TRAb and T3,T4,FT3,FT4,TSH levels in 68 pregnant women with Graves' disease and their newborns were detected by radio receptor assay(RRA) and electrical chemiluminescence immunoassay (ECLIA),respectively.Based on the maternal serum TRAb levels and the use of antithyroid drugs during pregancy, the newborns were divided into different groups.The incidence of neonatal thyroid dysfunction and its risk factors were analyzed. Results:The results showed the incidence of abnormal thyroid function of newborns was 29.4%(20/68).The proportion of neonatal thyroid dysfunction in women with high TRAb levels in the third trimester of pregnancy were significantly higher than these with normal TRAb(P0.01).In 23 newborns whose mothers were normal in serum TRAb levels and took no ATDs during pregnancy,only one case had thyroid dysfunction within two weeks after birth,while in other 45 newborns whose mothers had a high level of serum TRAb and/or took ATDs during pregnancy, 19 developed thyroid dysfunction within two weeks after birth. Conclusion:Neonatal thyroid function depends on the balance between the transplacental TRAb and ATDs. TRAb measurement in pregnant women with Graves' disease is of significance in evaluation of neonatal thyroid function. Elevated level of serum TRAb in the third trimester of pregnancy is a risk factor for neonatal thyroid dysfunction.     

检测Graves病孕妇血清促甲状腺激素受体抗体的临床意义

目的 探讨Graves病妊娠患者血清促甲状腺激素受体抗体（TRAb）水平和服用抗甲状腺药物（ATDs）对新生儿甲状腺功能异常的影响.方法 应用放射性受体法（RRA）和电化学发光免疫分析法（ECLIA）分别检测了68例Graves病孕妇及其新生儿血清TRAb和三碘甲状腺原氨酸（T3）、甲状腺素（T4）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）水平,根据母亲孕期血清TRAb水平和服用ATDs的情况对新生儿甲状腺功能异常发生率及影响因素进行分析.结果 新生儿甲状腺功能异常发生率为29.4%（20/68）,母亲妊娠晚期TRAb增高组其新生儿甲状腺功能异常发生率显著高于TRAb正常组（P〈0.01）.新生儿出生后5～14 d取静脉血测定TRAb和甲状腺功能,23例血清TRAb正常且未服ATDs的孕妇,其新生儿1例发生甲状腺功能异常;45例血清TRAb增高和（或）妊娠期间ATDs治疗的孕妇,其新生儿中19例发生新生儿甲状腺功能异常.结论 新生儿甲状腺功能取决于通过胎盘屏障的TRAb与ATDs之间的平衡.Graves病妊娠妇女血清TRAb的测定对评估新生儿甲状腺功能具有重要意义,妊娠晚期血清TRAb水平增高是新生儿甲状腺功能异常的一个危险因素.     

Recent progress in immune‐based interventions to prevent HIV‐1 transmission to children

Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV‐1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV‐1 infection. Thus, for the global community to achieve elimination of new paediatric HIV‐1 infections, innovative approaches need to be explored. Immune‐based approaches to prevention of mother‐to‐child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS‐free generation. Immune‐based interventions to prevent MTCT of HIV‐1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof‐of‐concept has been established over the last two decades that passively administered HIV‐1 Env‐specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune‐based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast‐Track 2030 goals to eliminate new paediatric HIV infections.