Growth of infants born to HIV-infected women in South Africa according to maternal and infant characteristics

Objective To evaluate growth parameters assessed by weight and length in HIV‐infected and HIV‐uninfected infants born to HIV‐infected mothers in South Africa from birth to 6 months of age. Methods We calculated z‐scores for weight‐for‐age (WAZ), length‐for‐age (LAZ) and weight‐for‐length (WLZ) among a cohort of 840 mother–infant dyads. Multivariable Cox proportional hazards models with time‐varying covariates were used to estimate the risk of falling z‐scores for WAZ, LAZ, and WLZ as a function of infant and maternal characteristics. Results By 6 months after birth, a fifth of infants had WAZ P < 0.001). The risk of WAZ falling 相似文献   

Mortality of HIV‐infected and uninfected children in a longitudinal cohort in rural south‐west Uganda during 8 years of follow‐up

Objectives To determine the impact of HIV on child mortality and explore potential risk factors for mortality among HIV‐infected and HIV‐exposed uninfected children in a longitudinal cohort in rural Uganda. Methods From July 2002 to March 2010, HIV‐infected and HIV‐exposed uninfected children aged 6 weeks–13 years were enrolled in an open population‐based clinical cohort. Antiretroviral therapy (ART) was introduced in 2005. Clinical and laboratory data were collected every 3 months. Person‐years at risk were calculated from time of enrolment until earliest date of ART initiation, death or last visit. Cox regression was used to estimate hazard ratios (HR) for mortality. Results Eighty‐nine (30.2%) HIV‐infected and 206 (69.8%) HIV‐exposed but uninfected children were enrolled. Twenty‐one children died. The mortality rate was six times higher in ART‐naive HIV‐infected children than in HIV‐exposed but uninfected children (HR = 6.4, 95% CI = 2.4–16.6). Among HIV‐infected children, mortality was highest in those aged <2 years. Decreasing weight‐for‐age Z (WAZ) score was the strongest risk factor for mortality among HIV‐infected children (HR for unit decrease in WAZ = 2.6, 95% CI = 1.6–4.1). Thirty‐five children (aged 7 months–15.6 years; median, 5.4 years) started ART. Conclusions Mortality among HIV‐infected children was highest among those aged <2 years. Intensified efforts to prevent mother‐to‐child transmission of HIV and ensure early HIV diagnosis and treatment are required to decrease child mortality caused by HIV in rural Africa.     

Lymphocyte subset changes between 3 and 15 months of age in infants born to HIV-seropositive women in South Africa

The evolution of T‐lymphocyte subsets during infancy in perinatally HIV‐infected African babies has not been previously described. In a hospital‐based cohort study, T‐lymphocyte subset changes were investigated in 72 South African black children born to HIV seropositive mothers. Sixteen (22.2%) children were classified as infected and 56 (77.8%) as uninfected by 18 months of age. Four (25%) of the infected infants died before the age of 9 months from HIV‐related disease.
The CD4 and CD8 T‐lymphocyte subsets, expressed in absolute numbers, as percentages, percentiles or as ratios, were clear indicators of HIV infection at all ages between 3 and 15 months. The most marked changes were a decreased percentage of CD4 cells and an increase in percentage of CD8 cells in the infected group. In the 4 infected infants who died, CD8 count and CD4:CD8 ratio clearly predicted poor clinical outcome at 3 months. Taken together, both CD4:CD8 ratio and CD4 percentage are reliable markers of HIV infection in an African paediatric population; however, a raised CD8 lymphocyte count rather than a CD4 count is a more specific prognostic marker of disease progression in HIV infected children.     

High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis

OBJECTIVES: To determine the natural history of HIV infection following peripartum single-dose nevirapine (sd-NVP) prophylaxis in a resource-limited country, and to assess implications for antiretroviral therapy (ART) roll-out programmes. METHODS: Infants of HIV-infected mothers in KwaZulu-Natal, South Africa, were tested on days 1 and 28 to detect intrauterine (IU) and intrapartum (IP) infection. Infant follow-up included monthly viral load and CD4 cell measurement. ART was initiated at infant CD4 cell% < or = 20%. RESULTS: In 740 infants born to 719 HIV-infected women, mother-to-child transmission (MTCT) was 10.3% (69% IU, 31% IP). Median viral load was higher in mothers of infants infected IP than IU (279 000 versus 86 600 copies/ml; P = 0.039) and lower in mothers of uninfected infants (median 26 750 copies/ml; P < 0.001). Peak viraemia was higher in infants infected IP than IU (5 160 000 versus 984 000 copies/ml; P < 0.001). Median viral load at birth in IU-infected infants (155 000 copies/ml) fell 1.4 log to 6510 copies/ml by day 5 and was beneath the detection limit using dried blood spot analysis in 38% of infants. CD4 cell% declined rapidly, to < or = 20% in 70% and < or = 25% in 85% [current World Health Organization (WHO) criteria for initiating ART] of infants by 6 months. CONCLUSIONS: MTCT was reduced by sd-NVP through an effect on IP transmission. Where MTCT occurred despite NVP, two-thirds of transmissions arose IU; IP-infected babies were born to mothers with very high viral load. Disease progression was particularly rapid, 85% infants meeting WHO criteria for ART within 6 months. These findings argue for more effective MTCT-prevention programmes in resource-limited countries.     

Early growth of infants of HIV-infected and uninfected Zambian women

OBJECTIVE: Parental HIV infection may affect even those exposed children who remain uninfected. We investigated early growth, an indicator of overall health, of infants born to Zambian mothers recruited for a study of breastfeeding and postpartum health. METHODS: HIV-infected and uninfected women in Lusaka were followed regularly from late pregnancy to 16 weeks postpartum. Infant weight and length were measured at birth, 6 and 16 weeks. Infant HIV status could not be specifically determined in this cohort so comparisons were between all infants of HIV-uninfected mothers (n = 184) and those infants of HIV-infected mothers who were known to be alive and showed no clinical evidence of HIV infection at age 2-4 years (n = 85). RESULTS: Most infants were exclusively or predominantly breastfed until 16 weeks. At all time points infants of HIV-infected mothers tended to have lower weight and length standard deviation (Z) scores (significant for weight at 6 weeks; P = 0.04), even after adjustment for their lower gestational age at birth, compared with infants of uninfected mothers. In multivariate analyses the major factors affecting weight or length at 6 or 16 weeks of age were birth weight or length, and maternal subclinical mastitis, primiparity and weight during pregnancy. CONCLUSIONS: Early growth of infants of HIV-infected mothers is less than that of uninfected mothers, in part associated with subclinical mastitis, and this effect cannot be overcome with intensive support of mothers to follow international recommendations regarding exclusive breastfeeding.     

Bacillus Calmette-Guérin immunization in infants born to HIV-1-seropositive mothers

During the prospective follow-up of 64 babies at risk for perinatal HIV-1 infection because their mothers were seropositive, and of 130 control babies whose mothers were seronegative, we studied the occurrence of complications of bacillus Calmette-Guérin (BCG) immunization and its ability to induce cutaneous reactivity to tuberculin. Babies born both to HIV-1-positive and HIV-1-negative mothers received BCG immunization during their first month of life according to the Expanded Programme on Immunization (EPI) recommendations. Local and regional complications of BCG vaccine were looked for at 3, 6 and 9 months after inoculation. A tuberculin skin test was performed at 6 or 9 months of age. Most babies born to HIV-1-positive mothers were later classified as infected or uninfected according to their clinical condition and/or serological status at 18 months of age. The mean duration of the follow-up was 36 months (range 30-40 months). No chronic or deep ulcerations at the site of injection or disseminated forms of BCG infection were observed. The frequency of BCG-related lymphadenitis in the group of HIV-1-infected children (24%) did not differ significantly from the group of uninfected children (19%; Fisher test: P = 0.73). In contrast, the tuberculin skin test responses were positive less often in the group of HIV-1-infected children (33%) than in the uninfected group (83%; Fisher test: P = 0.007). Because BCG vaccine appears to be safe--even when given to perinatally infected babies--continuation of the BCG immunization policies of the EPI is justified, especially in view of the growing incidence of tuberculosis as a complication of HIV infection.     

Failure to test children of HIV-infected mothers in South Africa: implications for HIV testing strategies for preschool children

Objectives To assess the uptake of HIV testing among preschool children with HIV‐positive mothers in a peri‐urban population‐based study in KwaZulu‐Natal, South Africa, an area of high HIV prevalence. Methods All children 4–6 years old and their primary caregivers from the area were invited to participate. All participants were asked about prior HIV testing and were offered counselling and voluntary HIV testing irrespective of previous testing. Twenty‐seven HIV‐infected mothers were interviewed to identify barriers to testing their children. Results One thousand five hundred and eighty‐three children (88% of eligible children) and their caregivers participated. Of the biological mothers, 86% were previously tested for HIV (27% tested positive). Among the surviving 244 children born to an infected mother, only 41% had been tested for HIV (23% tested positive). Subsequently, 90% of previously untested children of infected mothers underwent HIV testing (9.3% were positive). Overall seroprevalence among study children was 4.9%. All infected mothers interviewed endorsed the belief that children of HIV‐infected women should be tested for HIV. Women who missed opportunities for antenatal HIV testing reported no systematic testing of their children at later ages. Conclusions In this community with high HIV prevalence, HIV testing of children is infrequent despite high testing coverage among caregivers. The low proportion of children tested for HIV, particularly those of infected mothers, is of great concern as they are at high risk for morbidity and mortality associated with untreated childhood HIV infection. HIV testing programs should strengthen protocols to include children, especially for those who missed PMTCT opportunities in infancy.     

Longitudinal growth during the first 2 years of life in children born to HIV-infected mothers in Malawi, Africa

To evaluate the longitudinal growth patterns of infants born to HIV-infected and uninfected mothers in Malawi, Africa, 92 HIV-infected infants, 270 uninfected infants born to HIV-infected mothers, and 686 infants born to uninfected mothers between birth and 24 months of life were studied. Weight and length were evaluated longitudinally utilizing generalized estimating equations. HIV-infected children were compared with uninfected children born to HIV-infected and uninfected mothers, and to United States National Center for Health Statistics (NCHS) growth standards. Median weight and length-for-age of seronegative infants born to either seronegative or seropositive mothers approximated the NCHS median from birth to approximately 4 months of age. Median weight and length of HIV-infected infants deviated from the NCHS median at an earlier age, and the deviation was more pronounced than was observed for uninfected infants. Mean growth curves constructed by generalized estimating equations indicated that HIV-infected and uninfected infants born to HIV-infected mothers weighed less and were smaller than infants born to HIV-uninfected mothers initially. Mean weight and length of uninfected infants attained the median of infants born to uninfected mothers by 24 months of age, while HIV-infected infants remained below this median. The difference in mean weight-for-age for HIV-infected and uninfected infants born to HIV-infected mothers was statistically significant from birth. The difference in mean length-for-age was statistically significant after 5 months of age. Thus, although infants born to HIV-infected mothers were smaller and weighed less initially, uninfected infants caught up, while HIV-infected infants remained below the median, and the deficit in weight occurred earlier in life than the deficit in length.     

HIV感染母亲分娩婴幼儿的体格生长发育状况研究

目的了解艾滋病病毒（HIV）感染母亲分娩的婴幼儿的体格生长发育状况。方法对我国4个艾滋病高发省的7个县／区,HIV感染母亲分娩的活产婴幼儿,分别在出生时、3、6、9、12、15、18月龄进行随访调查及生长发育监测,分析18月龄存活婴幼儿的体格生长发育指标。结果2005—2008年,共调查18月龄存活婴幼儿154名,其中HIV感染婴幼儿22名,非感染婴幼儿132名。结果：（1）HIV感染婴幼儿在6—18月龄的身长、体重明显低于非HIV感染婴幼儿（P〈O．05）,年龄别头围的差别无统计学意义。（2）与世界卫生组织（WHO）儿童生长标准比较,非HIV感染婴幼儿中,男、女童6月龄前的年龄别体重与该标准无差别,6月龄后的年龄别体重高于该标准（P〈O．05）;年龄别体重z值（wAz）和身长别体重z值（WHz）在-0．1～1之间;男、女童12月龄内的年龄别身长与该标准的差别无统计学意义,15—18月龄身长低于该标准（P〈0．05）,年龄别身长z值（HAz）和年龄别头围Z值在-0．1～-1之间。（3）HIV感染男、女童各月龄的体重、头围与WHO标准的差别无统计学意义,15—18月龄身长低于该标准;随访期间wAZ在O．2～-0．6之间,3月龄内wAZ下降较快,之后处于低水平状态;HAZ在0．1～-1．7之间,呈下降趋势,在6—12月龄接近-1,15—18月龄低于-1。结论HIV感染母亲分娩的非HIV感染婴幼儿的体格生长不足,身长、头围发育较差,而HIV感染婴幼儿更为严重。     

HIV and child-bearing: clinical outcome and aspects of mother-to-infant transmission

Forty-four HIV-1-seropositive women and their children were followed-up and examined in connection with the course of pregnancy, mother-to-infant transmission of HIV and clinical outcome. Twelve out of 48 children were known to be infected and two children were lost to follow-up. Of the remaining 34 children, 22 are not infected, and 12 are clinically and immunologically normal at less than 18 months. There was no difference in intrauterine growth between infected and uninfected children. Forty-six per cent of the 39 mothers seen after delivery progressed to a more advanced stage of HIV infection during a mean follow-up time of 33 months after delivery. Although comparable in age, clinical and immunological status at delivery, and follow-up time, mothers of infected children had longer durations of HIV infection and were symptomatic and/or had low CD4 cell counts to a significantly greater extent at follow-up than mothers of uninfected children.     

Maternally transmitted HIV infection in children

We evaluated 16 children at high risk for AIDS because of mothers infected with HIV. Two children were persistently seropositive and had laboratory and clinical evidence of HIV infection but had no detectable infectious HIV in their peripheral blood mononuclear cells (PBMC). Seven children, all of whom had clinical and laboratory evidence of HIV infection, were seropositive and virus culture-positive. One child who died at 10 months of age of candida septicemia was HIV antibody-negative but HIV was grown from cultures of his PBMC. Six children had no serologic or virologic evidence of HIV infection; of these, four who were asymptomatic with normal laboratory studies were HIV antibody-positive up to 12 months of age but became antibody-negative by 15 months of age. These observations indicate that: (1) as many as 60% of infants of infected mothers may be infected with HIV; (2) maternal antibody can result in a false-positive or false-negative diagnosis of HIV infection in infants exposed in utero or perinatally, and (3) the use of viral cultures for HIV is valuable for the early diagnosis of maternally transmitted HIV infection.     

The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure

Objectives To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV‐infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. Methods Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV‐RNA monitoring are performed 6‐monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV‐RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months. Results Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21–84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%. Conclusion The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second‐line treatment in virologically suppressed children.     

Vertical transmission of HIV in New York State: a basis for statewide testing of newborns

Infants (n = 313) of HIV-infected mothers were enrolled (mean age 1.9 weeks, range 0-8 weeks) in a 3-year prospective study of vertical transmission. Fifty-six infants (17.9%) had laboratory and clinical evidence of HIV infection. Polymerase chain reaction (PCR) provided early and reliable identification of infected infants. Thirty-one of the 56 infected infants had specimens submitted when the infants were 4 weeks of age or less and 30 (97%) tested PCR positive. This percentage increased to 100% by 8 weeks of age when 51 of the 56 infected infants had specimens tested for that time period. Immune complex dissociation (ICD) antigen testing was a sensitive method for diagnosis of infection but only in infants older than 1 month. p24 antigen testing, although free of false positives, is less sensitive than either of the other methods. Among surrogate markers of HIV infection, elevation of soluble CD8 levels precedes an increase in immunoglobulin levels or a decline in CD4 T lymphocytes. Vertical transmission is significantly lower in Central and Western New York State than other regions. Transmission is significantly higher in low birthweight babies and in infants whose mothers have CD4 counts < 500. This study provided the basis for establishing a Pediatric HIV PCR Testing Service for the early diagnosis of HIV infection in neonates.     

Predicting perinatal HIV infection in young Brazilian infants: How accurate are signs, symptoms and immunological abnormalities?

Early identification of infants perinatally infected with HIV (HIV+) requires costly laboratory tests which are not widely available in countries with limited resources. We evaluated the utility of detection of non-specific HIV-related signs and symptoms and immunological abnormalities in the diagnosis of perinatal HIV infection in Brazilian infants younger than 10 months of age and followed from birth. A total of 27 HIV+ and 43 uninfected infants were studied. All infants exhibited one or more non-specific HIV-related findings at least once. HIV+ infants were more frequently symptomatic than HIV- infants only when older than 3 months. Combinations of clinical and immunological findings resulted in high sensitivity (85-100%) and low specificity (25-65%) rates for the diagnosis of HIV infection. Conversely, low CD4+ cell counts and hyperimmunoglobulinaemia showed low sensitivity (52%) and high specificity (100%) rates. In conclusion, the detection of similar findings in HIV- and HIV+ infants underscores the need of early confirmatory laboratory testing.     

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected children and infants in northern Tanzania

Objective To describe the contribution of paediatric HIV and of HIV co‐infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods. Methods During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV‐1 RNA PCR was performed on those aged <18 months. HIV‐infected patients also received serum cryptococcal antigen testing and had their CD4‐positive T‐lymphocyte count and percent determined. Results A total of 467 patients were enrolled whose median age was 2 years (range 2 months–13 years); Of those patients, 57.2% were female and 12.2% were HIV‐infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV‐uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively. Conclusion Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over‐diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co‐infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.     

Vertical transmission of human immunodeficiency virus is correlated with the absence of high-affinity/avidity maternal antibodies to the gp120 principal neutralizing domain.

Many, but not all, infants born to mothers infected with the human immunodeficiency virus (HIV) are infected in utero. We have now shown that mothers who have high-affinity/avidity antibodies directed toward the principal neutralizing domain (PND) of gp120 are less likely to transmit HIV to their children. An ELISA that preferentially measures the level of the biologically functioning, high-affinity/avidity antibodies against PND is described. In a retrospective study of 15 maternal/neonatal serum samples, the assay correctly identified the 4 uninfected and the 11 HIV-infected infants. Other clinical and laboratory parameters such as p24 antigen, phytohemagglutinin mitogenic index, and absolute surface antigen T4+ cell counts did not accurately predict HIV fetal transmission. In addition to introducing a promising diagnostic tool, this study provides the in vivo evidence that protective antibodies may prevent infection by HIV.     

Growth response to antiretroviral treatment in HIV‐infected children: a cohort study from Lilongwe,Malawi

Objective Malnutrition is common in HIV‐infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public‐sector clinic in Malawi. Methods All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex‐ and age‐standardized z‐scores were calculated for weight‐for‐age (WAZ) and height‐for‐age (HAZ). Predictors of growth were identified in multivariable mixed‐effect models. Results A total of 497 children started ART and were followed for 972 person‐years. Median age (interquartile range; IQR) was 8 years (4–11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART, median (IQR) WAZ and HAZ increased from ?2.1 (?2.7 to ?1.3) and ?2.6 (?3.6 to ?1.8) to ?1.4 (?2.1 to ?0.8) and ?1.8 (?2.4 to ?1.1) at 24 months, respectively (P < 0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Conclusions Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response.     

The reference range of CD4+ and CD8+ T-lymphocytes in healthy non-infected infants born to HIV-1 seropositive mothers; a preliminary study at Siriraj Hospital.

The results of CD4+, CD8+ T-lymphocyte values as percentage, number, and ratio were studied in infants aged 1 to 29 months. The 283 subsequent blood samples from 89 infants born to HIV-1 seropositive mothers were investigated. From 208 sequential samples of 70 healthy non-infected infants, the reference values of CD4+ and CD8+ T-lymphocytes have been established and compared to Caucasian reference values. The results were analysed in 4 difference age groups (1-5, 6-11, 12-17 and > or = 18 months). At age 12 months, CD4 number and percentage declined significantly while CD8 percent increased. At age 6 months CD4/CD8 ratio decreased. Of 19 infected infants CD4+ percentage and number as well as CD4/CD8 ratio declined at age 6 months and showed significant differences from uninfected infants. A significantly elevated CD8 percentage was demonstrated in infected infants at age of 12 months. In 9 infants who showed symptoms at age 6-18 months, the CD4 and CD8 values were different from the reference range and 6 of 9 patients showed lower CD4 percentage, CD4 number and reversed CD4/CD8 ratio before the symptoms appeared. In 10 infants who were asymptomatic at age 18 months, there was no evidence of immunosuppression at age 6 months or before. After age 6 months, lymphocyte subset values of some asymptomatic infected children were beyond the reference range. These preliminary findings should be very useful for monitoring children born to HIV infected mothers. The results of CD4+ and CD8+ T-lymphocytes in uninfected infants could be used as reference values for the Thai and other Southeast Asian pediatric populations.     

Retention of HIV‐infected and HIV‐exposed children in a comprehensive HIV clinical care programme in Western Kenya

Background To describe incidence rates (IR) and risk factors for loss‐to‐follow‐up (LTFU) among HIV‐infected and HIV‐exposed children in a large HIV treatment programme in Western Kenya. Methods The USAID‐AMPATH Partnership has enrolled >100 000 patients (20% children) at 23 clinic sites throughout western Kenya. LTFU is defined as being absent from the clinic for >3 months if on combination antiretroviral treatment (cART) and >6 months if not. Included in this analysis were children aged <14 years, HIV exposed or infected at enrolment, and enrolled between April 2002 and March 2009. The IR for LTFU are presented per 100 child‐years (CY) of follow‐up. Proportional hazards models with time‐independent and time‐dependent covariates were used to model factors associated with LTFU. Weight for height Z‐scores were calculated using EpiInfo, with severe malnutrition being defined as a Z‐score ≤?3.0. Immune suppression was defined as per WHO age‐specific categories. Results There were 13 510 children eligible for analysis, comprising 3106 children who at enrolment were HIV infected and 10 404 children who were HIV exposed. The overall IR of LTFU was 18.4 (17.8–18.9) per 100 CY. Among HIV‐infected children, 15.2 (13.8–16.7) and 14.1 (13.1–15.8) per 100 CY became LTFU, pre‐ and post‐cART initiation, respectively. The only independent risk factor for becoming LTFU among the HIV‐infected children was severe immune suppression (AHR: 2.17, 95% CI: 1.51–3.12). Among the HIV‐exposed children, 20.1 per 100 (19.4–20.7) became LTFU. Independent risk factors for LTFU among them were being severely low weight for height (AHR: 1.69, 95% CI: 1.25–2.28), being orphaned at enrolment (AHR: 1.57, 95% CI: 1.23–1.64), being CDC Class B or C (AHR: 1.41, 95% CI: 1.14–1.74), and having received cART (AHR: 1.56, 95% CI: 1.23–1.99). Protective against becoming LTFU among the HIV exposed were testing HIV positive (AHR: 0.26, 95% CI: 0.21–0.32), older age (AHR: 0.90, 95% CI: 0.85–0.96), enrolling in later time periods, and receiving food supplementation (AHR: 0.58, 95% CI: 0.32–1.04). Conclusions There is a high rate of LTFU among these highly vulnerable children, particularly among the HIV exposed. These data suggest that HIV‐infected and HIV‐exposed children are at especially high risk for LTFU if they are sick or malnourished.     

Stimulation of lung growth in fetuses with lung hypoplasia leads to altered postnatal lung structure in sheep

Our objective was to describe the respiratory complications, clinical findings, and chest radiographic changes in the first year of life in infected and uninfected children born to HIV-1-infected women. We prospectively followed a cohort of 600 infants born to HIV-1-infected women from birth to 12 months in a multicenter study. Of these, 93 infants (15.5%) were HIV-1-infected, 463 were uninfected, and 44 were of unknown status prior to death or loss to follow-up. The cumulative incidence ( +/- SE) of an initial pneumonia episode at 12 months was 24.1 +/- 4.7% in HIV-1-infected children compared to 1.4 +/- 0.6% in HIV-1-uninfected children (P < 0.001). The rate of Pneumocystis carinii pneumonia (PCP) was 9.5 per 100 child-years. The HIV-1 RNA load was not higher in the group that developed pneumonia in the first year vs. those who did not. Children who developed lower respiratory tract infections or PCP had increased rates of decline of CD4 cell counts during the first 6 months of life. Lower maternal CD4 cell counts were associated with higher rates of pneumonia, and upper and lower respiratory tract infections. The rates of upper respiratory tract infection and bronchiolitis/reactive airway disease in infected children were not significantly different than in uninfected children. At 12 months, significantly more HIV-1-infected than uninfected children had tachypnea and chest radiographs with nodular and reticular densities. There was no relationship between cytomegalovirus infection in the first year of life and radiographic changes or occurrences of pneumonia. In conclusion, despite a low incidence of PCP, rates of pneumonia remain high in HIV-infected children in the first year of life. The incidence of pneumonia in uninfected infants born to HIV-1-infected mothers is low. Chest X-ray abnormalities and tachypnea suggest that subacute disease is present in infected infants. Further follow-up is warranted to determine its nature.