The next generation of the World Health Organization's global antiretroviral guidance

The 2013 World Health Organization’s (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource‐limited settings. The most important new clinical recommendations include: treating adults, adolescents and older children earlier – starting ART in all individuals with a CD4 cell count of 500 cells/mm³ or less (but giving priority to those with advanced clinical disease or a CD4 cell count less than 350 cells/mm³); starting ART at any CD4 cell count in certain populations, including those with active TB (existing recommendation), Hepatitis B infection and severe chronic liver disease, HIV‐positive partners in serodiscordant couples (existing recommendation), pregnant and breastfeeding women, and children younger than 5 years of age; a preferred first‐line ART regimen of Tenofovir+3TC or FTC+ Efavirenz as a once‐daily fixed‐dose combination for adults, pregnant women, and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services, including strategies to improve retention in care, and adherence to ART; task‐shifting to address human resource gaps; decentralizing delivery of ART to primary health care, and integrating ART services within maternal and child health, TB or drug dependency clinics. There is additional guidance for programme managers on how to plan HIV programmes and use resources most efficiently.     

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.

     

Preferred antiretroviral drugs for the next decade of scale up

Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource‐limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late‐stage clinical development, hold great promise to simplify treatment in the short term. Over the longer term, newer technologies, such as long‐acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource‐limited settings.     

HIV transmission and retention in care among HIV‐exposed children enrolled in Malawi's prevention of mother‐to‐child transmission programme

Introduction : In Malawi, HIV‐infected pregnant and breastfeeding women are offered lifelong antiretroviral therapy (ART) regardless of CD4 count or clinical stage (Option B+). Their HIV‐exposed children are enrolled in the national prevention of mother‐to‐child transmission (PMTCT) programme, but many are lost to follow‐up. We estimated the cumulative incidence of vertical HIV transmission, taking loss to follow‐up into account. Methods : We abstracted data from HIV‐exposed children enrolled into care between September 2011 and June 2014 from patient records at 21 health facilities in central and southern Malawi. We used competing risk models to estimate the probability of loss to follow‐up, death, ART initiation and discharge, and used pooled logistic regression and inverse probability of censoring weighting to estimate the vertical HIV transmission risk. Results : A total of 11,285 children were included; 9285 (82%) were born to women who initiated ART during pregnancy. At age 30 months, an estimated 57.9% (95% CI 56.6–59.2) of children were lost to follow‐up, 0.8% (0.6–1.0) had died, 2.6% (2.3–3.0) initiated ART, 36.5% (35.2–37.9) were discharged HIV‐negative and 2.2% (1.5–2.8) continued follow‐up. We estimated that 5.3% (95% CI 4.7–5.9) of the children who enrolled were HIV‐infected by the age of 30 months, but only about half of these children (2.6%; 95% CI 2.3–2.9) were diagnosed. Conclusions : Confirmed mother‐to‐child transmission rates were low, but due to poor retention only about half of HIV‐infected children were diagnosed. Tracing of children lost to follow‐up and HIV testing in outpatient clinics should be scaled up to ensure that all HIV‐positive children have access to early ART.     

Five year neurodevelopment outcomes of perinatally HIV‐infected children on early limited or deferred continuous antiretroviral therapy

Introduction

Early antiretroviral therapy (ART) has improved neurodevelopmental outcomes of HIV‐infected (HIV‐positive) children; however, little is known about the longer term outcomes in infants commencing early ART or whether temporary ART interruption might have long‐term consequences. In the children with HIV early antiretroviral treatment (CHER) trial, HIV‐infected infants ≤12 weeks of age with CD4 ≥25% were randomized to deferred ART (ART‐Def); immediate time‐limited ART for 40 weeks (ART‐40W) or 96 weeks (ART‐96W). ART was restarted in the time‐limited arms for immunologic/clinical progression. Our objective was to compare the neurodevelopmental profiles in all three arms of Cape Town CHER participants.

Methods

A prospective, longitudinal observational study was used. The Griffiths mental development scales (GMDS), which includes six subscales and a global score, were performed at 11, 20, 30, 42 and 60 months, and the Beery‐Buktenica developmental tests for visual motor integration at 60 months. HIV‐exposed uninfected (HEU) and HIV‐unexposed (HU) children were enrolled for comparison. Mixed model repeated measures were used to compare groups over time, using quotients derived from standardized British norms.

Results

In this study, 28 ART‐Def, 35 ART‐40W, 33 ART‐96W CHER children, and 34 HEU and 39 HU controls were enrolled. GMDS scores over five years were similar between the five groups in all subscales except locomotor and general Griffiths (interaction p < 0.001 and p = 0.02 respectively), driven by early lower scores in the ART‐Def arm. At 60 months, scores for all groups were similar in each GMDS scale. However, Beery visual perception scores were significantly lower in HIV‐infected children (mean standard scores: 75.8 ART‐Def, 79.8 ART‐40W, 75.9 ART‐96W) versus 84.4 in HEU and 90.5 in HU (p < 0.01)).

Conclusions

Early locomotor delay in the ART‐Def arm resolved by five years. Neurodevelopmental outcomes at five years in HIV‐infected children on early time‐limited ART were similar to uninfected controls, apart from visual perception where HIV‐infected children scored lower. Poorer visual perception performance warrants further investigation.

     

Implementation of antiretroviral therapy guidelines for under-five children in Tanzania: translating recommendations into practice

Introduction

Paediatric antiretroviral therapy (ART) guidelines have been updated several times in recent years. We assessed implementation of ART guidelines among under-five children to inform the transition to universal paediatric ART in Tanzania.

Methods

We conducted a retrospective cohort analysis of infants (0 to 11 months) and children (12 to 59 months) enrolled between 2010 and 2012 using routinely collected data. Infants and children were initiated on ART according to the 2008 World Health Organization (WHO) recommendations/2009 Tanzania guidelines (universal ART for infants). Cumulative ART initiation incidence and correlates of ART initiation were examined using competing risk methods accounting for attrition (death or loss to follow-up). Kaplan-Meier methods and Cox regression models were used to examine attrition on ART and its correlates.

Results

A total of 1679 children were enrolled at 69 clinics: 469 (28%) infants and 1210 (74%) children. Infant cumulative ART initiation incidence was 59.6, 71.3 and 78.0% at one, three and six months of follow-up. Infants were more likely to start ART if enrolled in 2012 [adjusted sub-hazard ratio (AsHR)=2.2, 95% confidence interval (CI): 1.7 to 2.8] or 2011 (AsHR=1.8, 95% CI: 1.4 to 2.3) compared to 2010; they were more likely to start ART from prevention of mother-to-child HIV transmission (AsHR=1.6, 95% CI: 1.3 to 2.1) and inpatient wards (AsHR=1.5, 95% CI: 1.2 to 2.0) versus being enrolled from voluntary counselling and testing centres. Attrition at 12 months on ART was 33.9% and was more likely among infants with WHO Stage 4 [adjusted hazard ratio (AHR)=3.1. 95% CI: 1.8 to 5.2] and severe malnutrition (AHR=1.4, 95% CI: 1.0 to 1.9).Among 599 children eligible for ART at enrolment, cumulative ART initiation incidence was 51.8, 68.6 and 76.1% at one, three, and six months. Children were more likely to start ART if enrolled in 2012 (AsHR=1.8, 95% CI: 1.4 to 2.3) or 2011 (AsHR=1.5, 95% CI: 1.2 to 1.8) compared to 2010; they were more likely to start ART at primary health facilities (AsHR=1.5, 95% CI: 1.1 to 2.0) and less likely at urban facilities (AsHR=0.6, 95% CI: 0.5 to 0.9) and facilities without CD4 testing on site (AsHR=0.7, 95% CI: 0.5 to 0.9). Attrition at 12 months on ART was 23.1% and was more likely with severe malnutrition (AHR=1.8, 95% CI: 1.1 to 3.0), WHO Stage 4 (AHR=3.0, 95% CI: 1.0 to 8.5) and outpatient enrolees (AHR=1.7, 95% CI: 1.1 to 2.7).

Conclusions

Our findings suggest the gradual adoption of guidelines over calendar time. Interventions to expedite ART initiation and support retention on ART are needed.     

Virological response and resistances over 12 months among HIV‐infected children less than two years receiving first‐line lopinavir/ritonavir‐based antiretroviral therapy in Cote d’Ivoire and Burkina Faso: the MONOD ANRS 12206 cohort

Introduction : Lopinavir/ritonavir‐based antiretroviral therapy (ART) is recommended for all HIV‐infected children less than three years. However, little is known about its field implementation and effectiveness in West Africa. We assessed the 12‐month response to lopinavir/ritonavir‐based antiretroviral therapy in a cohort of West African children treated before the age of two years. Methods : HIV‐1‐infected, ART‐naive except for a prevention of mother‐to‐child transmission (PMTCT), tuberculosis‐free, and less than two years of age children with parent's consent were enrolled in a 12‐month prospective therapeutic cohort with lopinavir/ritonavir ART and cotrimoxazole prophylaxis in Ouagadougou and Abidjan. Virological suppression (VS) at 12 months (viral load [VL] <500 copies/mL) and its correlates were assessed. Result s : Between May 2011 and January 2013, 156 children initiated ART at a median age of 13.9 months (interquartile range: 7.8–18.4); 63% were from Abidjan; 53% were girls; 37% were not exposed to any PMTCT intervention or maternal ART; mother was the main caregiver in 81%; 61% were classified World Health Organization Stage 3 to 4. After 12 months on ART, 11 children had died (7%), 5 were lost‐to‐follow‐up/withdrew (3%), and VS was achieved in 109: 70% of children enrolled and 78% of those followed‐up. When adjusting for country and gender, the access to tap water at home versus none (adjusted odds ratio (aOR): 2.75, 95% confidence interval (CI): 1.09–6.94), the mother as the main caregiver versus the father (aOR: 2.82, 95% CI: 1.03–7.71), and the increase of CD4 percentage greater than 10% between inclusion and 6 months versus <10% (aOR: 2.55, 95% CI: 1.05–6.18) were significantly associated with a higher rate of VS. At 12 months, 28 out of 29 children with VL ≥1000 copies/mL had a resistance genotype test: 21 (75%) had ≥1 antiretroviral (ARV) resistance (61% to lamivudine, 29% to efavirenz, and 4% to zidovudine and lopinavir/ritonavir), of which 11 (52%) existed before ART initiation. Conclusions : Twelve‐month VS rate on lopinavir/ritonavir‐based ART was high, comparable to those in Africa or high‐income countries. The father as the main child caregiver and lack of access to tap water are risk factors for viral failure and justify a special caution to improve adherence in these easy‐to‐identify situations before ART initiation. Public health challenges remain to optimize outcomes in children with earlier ART initiation in West Africa.     

Loss to follow‐up among children and adolescents growing up with HIV infection: age really matters

Introduction : Globally, increasing numbers of HIV‐infected children are reaching adolescence due to antiretroviral therapy (ART). We investigated rates of loss‐to‐follow‐up (LTFU) from HIV care services among children as they transition from childhood through adolescence. Methods : Individuals aged 5–19 years initiated on ART in a public‐sector HIV clinic in Bulawayo, Zimbabwe, between 2005 and 2009 were included in a retrospective cohort study. Participants were categorized into narrow age‐bands namely: 5–9 (children), 10–14 (young adolescents) and 15–19 (older adolescents). The effect of age at ART initiation, current age (using a time‐updated Lexis expansion) and transitioning from one age group to the next on LTFU was estimated using Poisson regression. Results : Of 2273 participants, 1013, 875 and 385 initiated ART aged 5–9, 10–14 and 15–19 years, respectively. Unlike those starting ART as children, individuals starting ART as young adolescents had higher LTFU rates after moving to the older adolescent age‐band (Adjusted rate ratio (ARR) 1.54; 95% CI: 0.94–2.55) and similarly, older adolescents had higher LTFU rates after transitioning to being young adults (ARR 1.79; 95% CI: 1.05–3.07). In older adolescents, the LTFU rate among those who started ART in that age‐band was higher compared to the rate among those starting ART at a younger age (ARR = 1.70; 95% CI: 1.05, 2.77). This however did not hold true for other age‐groups. Conclusions : Adolescents had higher rates of LTFU compared to other age‐groups, with older adolescents at particularly high risk in all analyses. Age‐updated analyses that examine movement across narrow age‐bands are paramount in understanding how developmental heterogeneity in children affects HIV outcomes.     

The hard part we often forget: providing care to children and adolescents with advanced HIV disease

Introduction

Many children and adolescents living with HIV still present with severe immunosuppression with morbidity and mortality remaining high in those starting antiretroviral therapy (ART) when hospitalized.

Discussion

The major causes of morbidity and mortality in children living with HIV are pneumonia, tuberculosis, bloodstream infections, diarrhoeal disease and severe acute malnutrition. In contrast to adults, cryptococcal meningitis is rare in children under 5 years of age but increases in adolescence. In 2021, the World Health Organizations (WHO) consolidated guidelines for managing HIV disease and rapid ART included recommendations for children and adolescents. In addition, a WHO technical brief released in 2020 highlighted the various interventions that are specifically related to children and adolescents with advanced HIV disease (AHD). We discuss the common clinical presentations of children and adolescents with AHD with a focus on diagnosis, prevention and treatment, highlight some of the challenges in the implementation of the existing package of care, and emphasize the importance of additional research to address the needs of children and adolescents with AHD.

Conclusions

There are limited data informing these recommendations and an urgent need for further research on how to implement optimal strategies to ensure tailored approaches to prevent and treat AHD in children and adolescents. Holistic care that goes beyond a simple choice of ART regimen should be provided to all children and adolescents with AHD.     

Antiretroviral postnatal prophylaxis to prevent HIV vertical transmission: present and future strategies

Introduction

Maternal antiretroviral therapy (ART) with viral suppression prior to conception, during pregnancy and throughout the breastfeeding period accompanied by infant postnatal prophylaxis (PNP) forms the foundation of current approaches to preventing vertical HIV transmission. Unfortunately, infants continue to acquire HIV infections, with half of these infections occurring during breastfeeding. A consultative meeting of stakeholders was held to review the current state of PNP globally, including the implementation of WHO PNP guidelines in different settings and identifying the key factors affecting PNP uptake and impact, with an aim to optimize future innovative strategies.

Discussion

WHO PNP guidelines have been widely implemented with adaptations to the programme context. Some programmes with low rates of antenatal care attendance, maternal HIV testing, maternal ART coverage and viral load testing capacity have opted against risk-stratification and provide an enhanced PNP regimen for all infants exposed to HIV, while other programmes provide infant daily nevirapine antiretroviral (ARV) prophylaxis for an extended duration to cover transmission risk throughout the breastfeeding period. A simplified risk stratification approach may be more relevant for high-performing vertical transmission prevention programmes, while a simplified non-risk stratified approach may be more appropriate for sub-optimally performing programmes given implementation challenges. In settings with concentrated epidemics, where the epidemic is often driven by key populations, infants who are found to be exposed to HIV should be considered at high risk for HIV acquisition. All settings could benefit from newer technologies that promote retention during pregnancy and throughout the breastfeeding period. There are several challenges in enhanced and extended PNP implementation, including ARV stockouts, lack of appropriate formulations, lack of guidance on alternative ARV options for prophylaxis, poor adherence, poor documentation, inconsistent infant feeding practices and in inadequate retention throughout the duration of breastfeeding.

Conclusions

Tailoring PNP strategies to a programmatic context may improve access, adherence, retention and HIV-free outcomes of infants exposed to HIV. Newer ARV options and technologies that enable simplification of regimens, non-toxic potent agents and convenient administration, including longer-acting formulations, should be prioritized to optimize the effect of PNP in the prevention of vertical HIV transmission.     

“We are part of a family”. Benefits and limitations of community ART groups (CAGs) in Thyolo,Malawi: a qualitative study

Introduction : In 2012 Community ART Groups (CAGs), a community‐based model of antiretroviral therapy (ART) delivery were piloted in Thyolo District, Malawi as a way to overcome patient barriers to accessing treatment, and to decrease healthcare workers’ workload. CAGs are self‐formed groups of patients on ART taking turns to collect ART refills for all group members from the health facility. We conducted a qualitative study to assess the benefits and challenges of CAGs from patients’ and healthcare workers’ (HCWs) perspectives. Methods : Data were collected by means of 15 focus group discussions, 15 individual in‐depth interviews, and participant observation in 2 health centres. The 94 study participants included CAG members, ART patients eligible for CAGs who remained in conventional care, former CAG members who returned to conventional care and HCWs responsible for providing HIV care. Patient participants were purposively selected from ART registers, taking into account age and gender. Narratives were audio‐recorded, transcribed, and translated from Chichewa to English. Data were analyzed through a thematic analysis. Results : Patients and HCWs spoke favourably about the practical benefits of CAGs. Patient benefits included a reduced frequency of clinic visits, resulting in reduced transportation costs and time savings. HCW benefits included a reduced workload. Additionally peer support was perceived as an added value of the groups allowing not only sharing of the logistical constraints of drugs refills, but also enhanced emotional support. Identified barriers to joining a CAG included a lack of information on CAGs, unwillingness to disclose one's HIV status, change of residence and conflicts among CAG members. Participants reported that HIV‐related stigma persists and CAGs were seen as an effective strategy to reduce exposure to discriminatory labelling by community members. Conclusions : In this setting, patients and HCWs perceived CAGs to be an acceptable model of ART delivery. Despite addressing important practical barriers to accessing ART, and providing peer support, CAGs were not well known by patients and had a limited impact on reducing HIV‐related stigma. The CAG model of ART delivery should be considered in similar settings. Further measures need to be devised and implemented to address HIV‐related stigma.     

HIV treatment and care in resource‐constrained environments: challenges for the next decade

Many successes have been achieved in HIV care in low‐ and middle‐income countries (LMIC): increased number of HIV‐infected individuals receiving antiretroviral treatment (ART), wide decentralization, reduction in morbidity and mortality and accessibility to cheapest drugs. However, these successes should not hide existing failures and difficulties. In this paper, we underline several key challenges. First, ensure long‐term financing, increase available resources, in order to meet the increasing needs, and redistribute the overall budget in a concerted way amongst donors. Second, increase ART coverage and treat the many eligible patients who have not yet started ART. Competition amongst countries is expected to become a strong driving force in encouraging the least efficient to join better performing countries. Third, decrease early mortality on ART, by improving access to prevention, case‐finding and treatment of tuberculosis and invasive bacterial diseases and by getting people to start ART much earlier. Fourth, move on from WHO 2006 to WHO 2010 guidelines. Raising the cut‐off point for starting ART to 350 CD4/mm³ needs changing paradigm, adopting opt‐out approach, facilitating pro‐active testing, facilitating task shifting and increasing staff recruitments. Phasing out stavudine needs acting for a drastic reduction in the costs of other drugs. Scaling up routine viral load needs a mobilization for lower prices of reagents and equipments, as well as efforts in relation to point‐of‐care automation and to maintenance. The latter is a key step to boost the utilization of second‐line regimens, which are currently dramatically under prescribed. Finally, other challenges are to reduce lost‐to‐follow‐up rates; manage lifelong treatment and care for long‐term morbidity, including drug toxicity, residual AIDS and HIV‐non‐AIDS morbidity and aging‐related morbidity; and be able to face unforeseen events such as socio‐political and military crisis. An old African proverb states that the growth of a deep‐rooted tree cannot be stopped. Our tree is well rooted in existing field experience and is, therefore, expected to grow. In order for us to let it grow, long‐term cost‐effectiveness approach and life‐saving evidence‐based programming should replace short‐term budgeting approach.     

Multicentre analysis of second‐line antiretroviral treatment in HIV‐infected children: adolescents at high risk of failure

Introduction : The number of HIV‐infected children and adolescents requiring second‐line antiretroviral treatment (ART) is increasing in low‐ and middle‐income countries (LMIC). However, the effectiveness of paediatric second‐line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second‐line ART outcomes for children and assessed the need for paediatric third‐line ART. Methods : We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second‐line ART in LMIC, contacting the corresponding study groups and including patient‐level data on virologic and clinical outcomes. Kaplan–Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second‐line treatment. Results : We included 12 cohorts representing 928 children on second‐line protease inhibitor (PI)‐based ART in 14 countries in Asia and sub‐Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9–19.4) of children experienced virologic failure. Adolescents (10–18 years) had failure rates of 14.5 (95% CI 11.9–17.6) per 100 person‐years compared to 4.5 (95% CI 3.4–5.8) for younger children (3–9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, p < 0.001) and short duration of first‐line ART before treatment switch (aHR 0.64 and 0.53, p = 0.008, for 24–48 months and >48 months, respectively, compared to <24 months). Conclusions : In LMIC, paediatric PI‐based second‐line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI‐based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.     

Postnatal HIV transmission in breastfed infants of HIV‐infected women on ART: a systematic review and meta‐analysis

Introduction : To systematically review the literature on mother‐to‐child transmission in breastfed infants whose mothers received antiretroviral therapy and support the process of updating the World Health Organization infant feeding guidelines in the context of HIV and ART. Methods : We reviewed experimental and observational studies; exposure was maternal HIV antiretroviral therapy (and duration) and infant feeding modality; outcomes were overall and postnatal HIV transmission rates in the infant at 6, 9, 12 and 18 months. English literature from 2005 to 2015 was systematically searched in multiple electronic databases. Papers were analysed by narrative synthesis; data were pooled in random effects meta‐analyses. Postnatal transmission was assessed from four to six weeks of life. Study quality was assessed using a modified Newcastle‐Ottawa Scale (NOS) and GRADE. Results and discussion : Eleven studies were identified, from 1439 citations and review of 72 abstracts. Heterogeneity in study methodology and pooled estimates was considerable. Overall pooled transmission rates at 6 months for breastfed infants with mothers on antiretroviral treatment (ART) was 3.54% (95% CI: 1.15–5.93%) and at 12 months 4.23% (95% CI: 2.97–5.49%). Postnatal transmission rates were 1.08 (95% CI: 0.32–1.85) at six and 2.93 (95% CI: 0.68–5.18) at 12 months. ART was mostly provided for PMTCT only and did not continue beyond six months postpartum. No study provided data on mixed feeding and transmission risk. Conclusions : There is evidence of substantially reduced postnatal HIV transmission risk under the cover of maternal ART. However, transmission risk increased once PMTCT ART stopped at six months, which supports the current World Health Organization recommendations of life‐long ART for all.     

The changing epidemiology of the global paediatric HIV epidemic: keeping track of perinatally HIV-infected adolescents

The global paediatric HIV epidemic is shifting into a new phase as children on antiretroviral therapy (ART) move into adolescence and adulthood, and face new challenges of living with HIV. UNAIDS reports that 3.4 million children aged below 15 years and 2 million adolescents aged between 10 and 19 years have HIV. Although the vast majority of children were perinatally infected, older children are combined with behaviourally infected adolescents and youth in global reporting, making it difficult to keep track of their outcomes. Perinatally HIV-infected adolescents (PHIVA) are a highly unique patient sub-population, having been infected before development of their immune systems, been subject to suboptimal ART options and formulations, and now face transition from complete dependence on adult caregivers to becoming their own caregivers. As we are unable to track long-term complications and survival of PHIVA through national and global reporting systems, local and regional cohorts are the main sources for surveillance and research among PHIVA. This global review will utilize those data to highlight the epidemiology of PHIVA infection, treatment challenges and chronic disease risks. Unless mechanisms are created to count and separate out PHIVA outcomes, we will have few opportunities to characterize the negative consequences of life-long HIV infection in order to find ways to prevent them.     

Surgical management of clinical problems in children with HIV infection

HIV infection is a very actual disease widespread all over the world (40 million people), including up to 10 thousand Romanian, are infected with HIV; there are 950 HIV-infected patients in Oltenia, 450 of them are in our county (Dolj area), 80% of the HIV-infected persons are children. The authors are studying a group of 17 cases of HIV-infected children with surgical problems (Acute appendicitis, acute cholecystitis, pulmonary and kidney abscess, lymphadenophlegmons, abdominal tumours), which have been transferred to our department from the Infectious Diseases Clinic, between 1995-2004. The medical records of all patients were reviewed: strategies of management, particularity of antiretroviral therapy of children, and also strategies of prevention the perioperative HIV transmission. The most frequent cases were the lymphadenophleg mons (40%) and chronic abdominal pain (25%). The acute abdominal pathology consisted in 2 cases of acute appendicitis and 1 case of acute cholecystitis, which were successfully treated. The HIV infection remains in actuality, because there is not an efficient antiretroviral therapy. Surgeons planning treatment must consider the risks of the patient against the potential benefits of surgery.     

High risk of loss to follow‐up among South African children on ART during transfer,a retrospective cohort analysis with community tracing

Introduction : Decentralization of HIV care for children has been recommended to improve paediatric outcomes by making antiretroviral treatment (ART) more accessible. We documented outcomes of children transferred after initiating ART at a large tertiary hospital in the Eastern Cape of South Africa. Methods : Electronic medical records for all children 0–15 years initiating ART at Dora Nginza Hospital (DNH) in Port Elizabeth, South Africa January 2004 to September 2015 were examined. Records for children transferred to primary and community clinics were searched at 16 health facilities to identify children with successful (at least one recorded visit) and unsuccessful transfer (no visits). We identified all children lost to follow‐up (LTF) after ART initiation: those LTF at DNH (no visit >6 months), children with unsuccessful transfer, and children LTF after successful transfer (no visit >6 months). Community tracing was conducted to locate caregivers of children LTF and electronic laboratory data were searched to measure reengagement in care, including silent transfers. Results : 1,582 children initiated ART at median age of 4 years [interquartile range (IQR): 1–8] and median CD4+ of 278 cells/mm³ [IQR: 119–526]. A total of 901 (57.0%) children were transferred, 644 (71.5%) to study facilities; 433 (67.2%) children had successful transfer and 211 (32.8%) had unsuccessful transfer. In total, 399 children were LTF: 105 (26.3%) from DNH, 211 (52.9%) through unsuccessful transfer and 83 (20.8%) following successful transfer. Community tracing was conducted for 120 (30.1%) of 399 children LTF and 66 (55.0%) caregivers were located and interviewed. Four children had died. Among 62 children still alive, 8 (12.9%) were reported to not be in care or taking ART and 18 (29.0%) were also not taking ART. Overall, 65 (16.3%) of 399 children LTF had a laboratory result within 18 months of their last visit indicating silent transfer and 112 (28.1%) had lab results from 2015 to 2016 indicating current care. Conclusion : We found that only two‐thirds of children on ART transferred to primary and community health clinics had successful transfer. These findings suggest that transfer is a particularly vulnerable step in the paediatric HIV care cascade.