C Thorne

Response to combination antiretroviral therapy: variation by age.

Objective:To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. Design and setting:Multicohort collaboration of 33 European cohorts. Subjects:Forty-nine thousand nine hundred and twenty-one antiretroviral-naive individuals starting combination antiretroviral therapy from 1998 to 2006. Outcome measures:Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/μl (immunological response) and new AIDS/death were analysed using survival methods. Ten age strata were chosen: less than 2, 2–5, 6–12, 13–17, 18–29, 30–39 (reference group), 40–49, 50–54, 55–59 and 60 years or older; those aged 6 years or more were included in multivariable analyses. Results:The four youngest age groups had 223, 184, 219 and 201 individuals and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2–54.1%) and 59.2% (58.7–59.6%) had experienced a virological and immunological response. The probability of virological response was lower in those aged 6–12 (adjusted hazard ratio: 0.87) and 13–17 (0.78) years, but was higher in those aged 50–54 (1.24), 55–59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults and reduced in those 60 years or older. Those aged 55–59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. Conclusion:Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy CD4 cell counts, may place this group at increased clinical risk. The poorer virological responses in children may increase the likelihood of emergence of resistance.

Earlier initiation of ART and further decline in mother-to-child HIV transmission rates, 2000-2011

Objectives:To analyze mother-to-child HIV transmission (MTCT) rates over time in light of changes in management, demographic, and pregnancy characteristics. Design:Population-based surveillance data on diagnosed HIV-positive women and their infants are routinely collected in the UK and Ireland. Methods:A total of 12u200a486 singleton pregnancies delivered in 2000–2011 were analyzed. HIV infection status was available for 11u200a515 infants (92.2%). Results:The rate of MTCT declined from 2.1% (17/816) in 2000–2001 to 0.46% (nine of 1975, 95% confidence interval: 0.21–0.86%) in 2010–2011 (trend, Pu200a=u200a0.01), because of a combination of factors including earlier initiation of antenatal combination antiretroviral therapy (cART). Excluding 63 infants who were breastfed or acquired HIV postnatally, MTCT risk was significantly higher for all modes of delivery in women with viral load of 50–399u200acopies/ml (1.0%, 14/1349), compared with viral load of less than 50u200acopies/ml (0.09%, six of 6347, Pu200a<0.001). Among the former (viral load 50–399u200acopies/ml), the risk of MTCT was 0.26% (two of 777) following elective cesarean section and 1.1% (two of 188) following planned vaginal delivery (Pu200a=u200a0.17), excluding in-utero transmissions. MTCT probability declined rapidly with each additional week of treatment initially, followed by a slower decline up to about 15 weeks of cART, with substantial differences by baseline viral load. Conclusion:MTCT rates in the UK and Ireland have continued to decline since 2006, reaching an all-time low of 5 per 1000 in 2010–2011. This was primarily because of a reduction in transmissions associated with late initiation or nonreceipt of antenatal cART, and an increase in the proportion of women on cART at conception.

Antiretroviral therapy and preterm delivery—a pooled analysis of data from the United States and Europe

Please cite this paper as: Townsend C, Schulte J, Thorne C, Dominguez K, Tookey P, Cortina‐Borja M, Peckham C, Bohannon B, Newell M, for the Pediatric Spectrum of HIV Disease Consortium, the European Collaborative Study and the National Study of HIV in Pregnancy and Childhood. Antiretroviral therapy and preterm delivery—a pooled analysis of data from the United States and Europe. BJOG 2010;117:1399–1410.

Central Asia: hotspot in the worldwide HIV epidemic

The HIV epidemic in central Asia (Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan) has accelerated since 2000. This expansion in the epidemic is largely attributable to escalating injection drug use, reflecting central Asias geographic position along major drug trafficking routes. Although up to 75% of cumulative HIV cases have been among injection drug users (IDUs) so far, HIV infections are increasing in other population groups, including female sex workers and their clients, prisoners, and migrants. Among IDUs, risky injecting practices are highly prevalent, and the intersecting epidemic of sexually transmitted infections, particularly syphilis, highlights the potential for sexual transmission of HIV to bridging populations. Few HIV cases in children have been reported so far, with most resulting from nosocomial outbreaks in hospital settings. Some recent progress has been made towards scaling-up prevention, treatment, and care services, including harm reduction for IDUs, although key challenges remain.

CD4 cell response to antiretroviral therapy in children with vertically acquired HIV infection: is it associated with age at initiation?

BACKGROUNDnConsiderable uncertainty remains as to whether early initiation of antiretroviral therapy (ART) in children with vertically acquired human immunodeficiency virus (HIV) infection increases the benefit in terms of immunological response.nnnMETHODSnThe association between immunological outcome and early initiation of and/or more-potent ART was investigated, using age-standardized z scores for CD4 cell counts (hereafter, CD4 z scores), in 131 HIV-infected children enrolled in the European Collaborative Study, a birth cohort study.nnnRESULTSnMedian age at initiation of the most-potent ART was 4 years (range, 0.1-15.5 years). Initiation of treatment after 5 months of age resulted in nonsignificantly lower CD4 z scores 6 months after initiation. Time to a 20% increase in CD4 z score was associated with age at initiation of the most-potent ART (adjusted hazard ratios [AHRs], 0.37 [P<.01] and 0.43 [P = .05] for 5 months-5 years of age and >5 years of age, respectively, compared with <5 months of age), ethnicity (AHR, 0.48 [P = .01], for black vs. white), and highly active ART (HAART) with or without prior ART (AHRs, 3.16 [P<.01] and 3.95 [P<.001], vs. mono or dual ART, respectively). The risk of subsequent deterioration of CD4 z score was similar for children who initiated ART in different age groups ( chi2 = 0.824; P = .82).nnnCONCLUSIONSnWe confirm the effectiveness of HAART with respect to the recovery of CD4 cell count and suggest a benefit of initiating ART before the age of 5 months. Age at initiation of the most-potent ART was not associated with the likelihood of sustaining the recovery of CD4 cell count.

Level and pattern of HIV-1-RNA viral load over age: Differences between girls and boys?

Objective To estimate RNA viral load patterns over age in vertically infected children that account for between- and within-individual variation, treatment and assay cut-off detection level. To investigate possible sex-based differences. Design A total of 118 infected children with 894 RNA viral load measurements enrolled in the European Collaborative Study were prospectively followed from birth for up to 15 years. Methods Fractional polynomial and mixed effects models with censored data to assess the non-linear pattern of viral load over age, allowing for repeated measures. Results The RNA viral load peaked at approximately 3 months of age, and gradually declined thereafter. The sex by age interaction was significant (χ2 = 19.7, P < 0.001); viral load peaked higher for girls than boys, but after 4 years the RNA load was consistently 0.25–0.5 log10 lower for girls than boys. The effects of sex and treatment on viral load vary over age (χ2 = 6.31, P = 0.043). Sex differences in RNA viral load relating to measurement without treatment were more pronounced than those under treatment. Disease progression was more rapid for girls than for boys up to the age of 4 years, and less rapid thereafter; the overall difference was not statistically significant. Conclusion Differences in RNA viral load over age between untreated boys and girls may have implications for policies for the initiation of antiretroviral therapy, but do not seem to translate into differences in progression to serious disease. The findings would suggest underlying biological explanations, which need further investigation.

Hepatitis B or hepatitis C coinfection in HIV-infected pregnant women in Europe

The aim of the study was to investigate the prevalence of and risk factors for hepatitis C or B virus (HCV or HBV) coinfection among HIV‐infected pregnant women, and to investigate their immunological and virological characteristics and antiretroviral therapy use.

Are there gender and race differences in cellular immunity patterns over age in infected and uninfected children born to HIV-infected women?

This study investigated whether age-related patterns of immunologic markers in 1488 uninfected (9789 measurements) and 186 infected (3414 measurements) children differed by gender and race. CD4+, CD8+, and absolute lymphocytes by HIV infection status, gender, and race were assessed using linear mixed-effects natural cubic spline models, allowing for prematurity and maternal CD4+ cell count. In uninfected children, levels of all 3 markers peaked twice in the first few months of life, declining to adult levels by around 8 years of age; uninfected boys and uninfected black children had significantly reduced CD4+ and absolute lymphocyte counts; the gender difference was especially pronounced in black children. Infected children had substantially lower levels and distinctly different patterns; with, e.g., by age 6 months CD4+ cell counts nearly 1200 per mm3 lower than in uninfected infants. Levels also significantly differed by gender and race for infected children, although for gender in the opposite direction. The gender and race differences in CD4+ levels were not explained by a general lymphocytosis nor were they confounded by treatment. These substantial differences in immunologic markers may reflect underlying genetic influence on the cellular immune system and may have implications for clinical decisions about therapeutic management.

Increasing likelihood of further live births in HIV-infected women in recent years.

Objectiveu2003 To examine how the subsequent childbearing of HIV‐infected mothers enrolled in the European Collaborative Study (ECS) has changed over time and identify factors predictive of further childbearing.

Social care of children born to HIV-infected mothers in Europe

Children of HIV-infected women are likely to be profoundly affected by their mothers infection, regardless of their own infection status and their number will increase with the spread of infection among women in Europe. This article describes the family circumstances and social care of 1,123 children born to HIV-infected women enrolled in the European Collaborative Study and followed prospectively from birth. Most mothers were white, married or cohabiting, asymptomatic and had a history of drug use, with 45% currently using injecting drugs at the time of enrollment. Seventy percent of children were cared for by their mothers and/or fathers consistently in their first four years of life, but by age eight an estimated 60% will have lived away from their parents (i.e. with foster or adoptive parents, other relatives or in an institution). Whether or not a child was infected did not influence the likelihood of living in alternative care. Maternal injecting drug use, single parenthood and health status were the major reasons necessitating alternative care. The type of alternative care varied according to maternal characteristics, childs age and geographic location. The mothers of 98 children had died and average age at maternal death was four years.