Cohort Of HIV-infected Children Research Articles

Subclinical Atherosclerosis and Markers of Immune Activation in HIV-Infected Children and Adolescents

HIV-infected adults display increased cardiovascular disease, probably driven by inflammation and immune activation. These relationships have not been addressed in vertically HIV-infected children and adolescents, a population at very high risk for long-term non-AIDS complications. Carotid intima media thickness (IMT) was measured in a cohort of HIV-infected children and adolescents and healthy controls. C-reactive protein and markers of immune activation (CD38⁺HLA-DR⁺) and immune senescence (CD28⁻CD57⁺) were determined. One hundred fifty HIV-infected patients and 150 controls were included, 64.8% female. IMT was thicker in HIV-infected patients (0.434 mm ± 0.025 vs. 0.424 mm ± 0.018, P < 0.001). After adjustment by age, sex, body mass index, and smoking status, HIV infection was independently associated with thicker IMT (odds ratio, 2.28; 95% confidence interval: 1.25 to 4.13; P = 0.007). Among HIV-related variables, a low CD4 nadir was related to an increased IMT. Although HIV-infected subjects presented higher frequencies of activated CD4⁺ and CD8⁺ T cells (P = 0.002 and P = 0.087, respectively), no relation was found between IMT and inflammation, immune activation, or senescence. Structural changes of the vasculature present early in vertically HIV-infected subjects as well as immune activation and senescence. These patients should be carefully monitored for the prompt detection and early treatment of cardiovascular disease.

Long-term Effectiveness of Combination Antiretroviral Therapy and Prevalence of HIV Drug Resistance in HIV-1–infected Children and Adolescents in Rwanda

To determine the long-term outcomes of treatment and prevalence of genotypic drug resistance in children and adolescents on combination antiretroviral therapy. A cross-sectional study (September 2009 to October 2010) in which clinical, immunologic and virologic outcomes were assessed at a single-study visit and through patient records in a cohort of HIV-infected children and adolescents. Risk factors for clinical and immunologic responses and virologic outcome were evaluated using logistic regression, and the accuracy of clinical and immunologic criteria in identifying virologic failure was assessed. Four hundred twenty-four patients were enrolled with a median age of 10.8 years (range: 1.7-18.8) and a median duration on combination antiretroviral therapy of 3.4 years (range: 1.0-8.1). Thirty-three percent were stunted and 17% underweight. Eighty-four percent (95% confidence interval: 79-87) of children >5 years had CD4 ≥350 cells/mm and in 74% (95% confidence interval: 62-84) of younger children CD4% was ≥25. CD4 values and age at combination antiretroviral therapy initiation were independently associated with CD4 outcomes; 124 (29%) had HIV-1 RNA ≥1000 copies/mL, with no significant predictors. Sensitivity for weight-for-age and height-for-age and CD4 cells (<350/mm) remained under 50% (15-42%); CD4 cells showed the best specificity, ranging from 91% to 97%. Of 52 samples tested, ≥1 mutations were observed in 91% (nucleoside reverse transcriptase inhibitors) and 95% (non-nucleoside reverse transcriptase inhibitors); 1 to 2 thymidine analogue-associated mutations were detected in 16 (31%) and ≥3 thymidine analogue-associated mutations in 7 (13%). Nearly 1 in 3 children showed virologic failure, and >10% of the subgroup of children with treatment failure in whom genotyping was performed demonstrated multiple HIV drug resistance mutations. Neither clinical condition nor CD4 cells were good indicators for treatment failure.

Impact of expanded antiretroviral use on incidence and prevalence of tuberculosis in children with HIV in Kenya

Antiretroviral therapy (ART) reduces pulmonary tuberculosis (PTB) in human immunodeficiency virus (HIV) infected children. Recent ART recommendations have increased the number of children on ART. To determine the prevalence and incidence of TB in HIV-infected children after the implementation of expanded ART guidelines. A prospective cohort study including HIV-infected children aged 6 weeks to 14 years was conducted in Kenya. The primary outcome measure was clinically diagnosed TB. Study participants were screened for prevalent TB at enrollment using Kenya's national guidelines and followed at monthly intervals to detect incident TB. Predictors of TB were assessed using logistic regression and Cox proportional hazards regression. Of 689 participants (median age 6.4 years), 509 (73.9%) were on ART at baseline. There were 51 cases of prevalent TB (7.4%) and 10 incident cases, with over 720.3 child-years of observation (incidence 1.4 per 100 child-years). Months on ART (adjusted hazard ratio [aHR] 0.91, P = 0.003; aOR 0.91, P< 0.001) and months in care before ART (aHR 0.87, P= 0.001; aOR 0.92, P < 0.001) were protective against incident and prevalent TB. ART was protective against TB in this cohort of HIV-infected children with high levels of ART use. Optimal TB prevention strategies should emphasize early ART in children.

Seroprevalence of hepatitis B in a cohort of HIV-infected children and adults in Swaziland

Hepatitis B virus (HBV) is an important co-morbidity in the HIV epidemic. A retrospective chart review was performed of HIV-infected patients with no previous antiretroviral history enrolled in a Swaziland clinic from January 2009 to May 2011. The seroprevalence of HBV surface antigen (HBsAg) was calculated and the data were analyzed using Mann-Whitney U and Fisher's exact tests. A total of 1282 patients were included in analysis. Five hundred were children aged <15 years. Overall HBsAg seroprevalence was 3.7% (1.4% of children and 5.1% of adults). Prevalence in under-5s was low (0.4%). Among adult women and men, prevalence was 4.2% and 9.8%, respectively (P = 0.022). Median alanine aminotransferase level was 19 U/L in the HBsAg-negative adults and 25 U/L in the HBsAg-positive adults (P = 0.005). Given the number of patients found to be HBsAg-positive, especially among adults, it is important for antiretroviral programmes to consider universal screening and strategically utilize medications that have been found effective in treating both HBV and HIV.

Adherence and Viral Suppression Among Infants and Young Children Initiating Protease Inhibitor-based Antiretroviral Therapy

High levels of adherence to antiretroviral therapy are considered necessary to achieve viral suppression. We analyzed data from a cohort of HIV-infected children who were <2 years of age receiving protease inhibitor-based antiretroviral therapy to investigate associations between viral suppression and adherence ascertained using different methods. Data were from the prerandomization phase of a clinical trial in South Africa of HIV-infected children initiating either ritonavir-boosted lopinavir (LPV/r) or ritonavir-based antiretroviral therapy. At scheduled visits during the first 24 weeks of enrollment, study pharmacists measured quantities of medications returned to the clinic. Caregivers answered questionnaires on missed doses and adherence barriers. Associations between adherence and viral suppression (HIV-1 RNA <400 copies/mL) were investigated by regimen. By 24 weeks, 197 of the 269 (73%) children achieved viral suppression. There was no association between viral suppression and caregiver reported missed doses or adherence barriers. For children receiving the LPV/r-based regimen, medication return adherence to each of the 3 drugs in the regimen (LPV/r, lamivudine or stavudine) individually or together was associated with viral suppression at different adherence thresholds. For example, <85% adherence to any of the 3 medications significantly increased odds of lack of viral suppression (odds ratio: 2.30, 95% confidence interval: 1.30-4.07, P = 0.004). In contrast, for children receiving the ritonavir-based regimen, there was no consistent pattern of association between medication return and viral suppression. Caregiver reports of missed doses did not predict virologic response to treatment. Pharmacist medication reconciliation correlated strongly with virologic response for children taking a LPV/r-based regimen and appears to be a valid method for measuring pediatric adherence.

Neurocognitive function in HIV-positive children in a developing country

We aimed to characterize neurological outcomes and determine the prevalence of HIV encephalopathy in a cohort of HIV-infected children in Jamaica. Data for 287 HIV-infected children presenting between 2002 and 2008 were reviewed and neurological outcomes characterized. A nested case-control study was conducted between July and September 2009 used 15 randomly selected encephalopathic HIV-infected children aged 7-10 years and 15 matched controls (non-encephalopathic HIV-infected). Their neurocognitive functions were evaluated using clinical assessment and standardized tests for intelligence, short term memory (visuo-spatial and auditory), selective attention, and fine motor and coordination functions. Outcomes were compared using Fisher's exact test and the Mann-Whitney U-test. Sixty-seven (23.3%) children were encephalopathic. The median age at diagnosis of HIV encephalopathy was 1.6 years (interquartile range (IQR) 1.1-3.4 years). Predominant abnormalities were delayed milestones (59, 88.1%), hyperreflexia (59, 86.5%), spasticity (50, 74.6%), microcephaly (42, 61.7%), and quadriparesis (21, 31.3%). The median age of tested children was 8.7 years (IQR 7.6-10.8 years) in the encephalopathic group and 9 years (IQR 7.4-10.7 years) in the non-encephalopathic group. Encephalopathic children performed worse in all domains of neurocognitive function (p<0.05). A high prevalence of HIV encephalopathy was noted, and significant neurocognitive dysfunction identified in encephalopathic children. Optimized management through the early identification of neurological impairment and implementation of appropriate interventions is recommended to improve quality of life.

Resource utilization and direct costs of pediatric HIV in Italy

This multicenter, prospective, observational study assessed the global economic impact of HIV care in a large cohort of HIV-infected children and adolescents in Italy. Three pediatric departments of reference participated on a voluntary basis. Centers were asked to enroll all their children during the period April 2010–March 2011. At enrollment, a pediatrician completed a questionnaire for each patient, including the type of service at access (outpatient consultation or day hospital), laboratory tests, instrumental examinations, specialists' consultations, antiretroviral therapy and opportunistic illness prophylaxis. Eligible patients had a confirmed diagnosis of HIV infection caused by direct vertical maternal-fetal transmission, their age ranging from 0 to 24 years. Since patients routinely have quarterly check-ups in all three centers, we adopted a three-month time horizon. Health-care services were priced using outpatient and inpatient tariffs. Drug costs were calculated by multiplying the daily dose by the public price for each active ingredient. A total of 142 patients were enrolled. More than half the patients were female and the mean age was 14 years, with no significant differences by center. There were substantial differences in health-care management among the three centers, particularly as regards the type of access. One center enrolled the majority of its patients in day-hospital and prescribed a large number of clinical tests, while children accessed another center almost exclusively through outpatient consultation. Drug therapy was the main cost component and was very similar in all three centers. The day-hospital was the second highest cost component, much higher than outpatient consultation (including examinations), leading to significant differences between total costs per center. These findings suggest that a recommendation to the Italian National Health Service would be to use more outpatient consultation for patients' access in order to increase their efficiency in treating pediatric HIV infection.

Efficacy and safety of a dual boosted protease inhibitor-based regimen, atazanavir and fosamprenavir/ritonavir, against HIV: experience in a pediatric population

BackgroundAlthough dual-boosted protease inhibitors regimen is not recommended in children with HIV infection, such a strategy could be useful in subjects with a complex resistance profile. This study was aimed at assessing the long term efficacy and safety of a double-boosted protease inhibitor combination, fosamprenavir (fAVP) and atazanavir/ritonavir (ATV/r) in a cohort of HIV-infected children and adolescents who had failed with nucleoside reverse transcriptase inhibitors.MethodsSeven vertically infected children and adolescents who had previously failed highly active antiretroviral therapy and were resistant to nucleoside reverse transcriptase inhibitors, received a dual protease inhibitor (PI) regimen including fAVP plus ATV/r for 42 months. The patients were assessed at baseline, every month for the first 24 weeks of therapy and every 3 months until month 32. Physical examination, CD4+ cell count, HIV-RNA viral load, lipid profile and hepatic function were assessed throughout the follow up.ResultsDuring the study no serious adverse events were reported. CD4 absolute number increased over-time in all subjects. At baseline the median HIV-RNA was 6562 cp/mL (ranging 1048 -102772 cp/mL) and rapidly decreased below the limit of detection (50 cp/mL) after 2 months of the new treatment and remained undetectable in all cases through the entire study period. At the beginning of the study all cases showed a normal lipid profile. During the study period, 4/7 subjects showed total cholesterol, low density lipoprotein and triglyceride levels >97th cent.le for the males and 94th cent.le for the females. HDL cholesterol showed protective values. Hepatic enzymes remained stable during the entire observation, whereas total bilirubin showed toxicity II/III grade in 6/7 subjects. No change in fat redistribution and insulin resistance was observed.ConclusionDual-boosted protease inhibitor therapy was virologically and immunologically effective and it could be considered as a possible alternative to a rescue regimen in children and adolescents. However, hypercholesterolemia and hypertriglyceridemia need close follow-up and may limit the use of this therapeutic option.

Renal function in HIV-infected children and adolescents treated with tenofovir disoproxil fumarate and protease inhibitors

BackgroundKidney disease is an important complication in HIV infected people, and this may be related to infection or antiretroviral therapy (ART). Our aim is to assess renal function in HIV infected paediatric patients, who may be particularly affected and are likely to take ART for longer than adults, and investigate the long term role of Tenofovir Disoproxil Fumarate (TDF) alone or co-administered with Ritonavir-boosted Protease Inhibitors (PI).MethodsSerum creatinine, phosphate and potassium levels, with estimated Glomerular Filtration Rate (eGFR), had been prospectively evaluated for 2 years in a cohort of HIV infected children and adolescents (age 9-18) on ART, and data analyzed according to the exposure to TDF or simultaneous TDF and PI.ResultsForty-nine patients were studied (57% female, mean age 14). Sixty-three percent were treated with ART containing TDF (Group A), and 37% without TDF (Group B); 47% with concomitant use of TDF and PI (Group C) and 53% without this combination (Group D). The groups didn't differ for age, gender or ethnicity. The median creatinine increased in the entire cohort and in all the groups analyzed; eGFR decreased from 143.6 mL/min/1.73 m2 at baseline to 128.9 after 2 years (p = 0.006) in the entire cohort. Three patients presented a mild eGFR reduction, all were on TDF+PI. Phosphatemia decreased significantly in the entire cohort (p = 0.0003) and in TDF+PI group (p = 0.0128) after 2 years. Five patients (10%) developed hypophosphatemia (Division of Acquired Immune Deficiency AE grade 1 or 2), and four of them were on TDF+PI.ConclusionsRenal function decrease and hypophosphatemia occur over time in HIV infected children and adolescents on ART. The association with co-administration of TDF and PI appears weak, and further studies are warranted.

Identifying missed opportunities for early intervention among HIV-infected paediatric admissions at Chris Hani Baragwanath hospital, Soweto, South Africa

Background and design. HIV is a major contributor to childhood morbidity and mortality in South Africa. We describe HIV prevalence, disease profile, outcome and missed opportunities for early intervention in a cohort of HIV-infected children admitted to Chris Hani Baragwanath Hospital’s general paediatric wards between 1 October and 31 December 2007. &#x0D; &#x0D; Results. Of 1 510 admissions, 446 (29.5%) were HIV-infected. Many children (238, 54.1%) were newly diagnosed in hospital and most had advanced HIV disease (405, 92%). The principal admission diagnoses were pneumonia (165, 37.5%), gastro-enteritis (97, 22%), sepsis (86, 19.5%) and tuberculosis (92, 21%). Of children identified as HIV infected before admission, 128/202 (63.4%) were not accessing antiretroviral treatment (ART), although 121/128 (94.5%) met ART eligibility criteria. Of 364 ART-naïve eligible children, only 15 (4.1%) were commenced on ART as inpatients. Problems with PMTCT implementation in infants under 6 months (N=166) included lack of maternal antenatal HIV testing (51, 30.7%); poor uptake of maternal/infant nevirapine prophylaxis (60, 36.2%); limited use of co-trimoxazole (CTX) prophylaxis (44/147, 29.9%); and delayed infant HIV polymerase chain reaction testing (98/147, 87.5%). Of infants known to be HIV infected prior to hospitalisation, 37/51 (73%) had not initiated ART. The in-hospital case fatality rate (CFR) among HIV-infected children was triple that of the combined HIV-uninfected, exposed and unknown group (12% v. 3.6%). Infants

Evaluation of long-term immunological and virological response to highly active antiretroviral therapy in a cohort of HIV infected children

Background CD4 T cells and HIV-1 RNA count are important markers of HIV progression and help clinical decision-making on how to conduct antiretroviral therapy. Methods We studied the long-term outcomes of viral and immune response of naïve children starting HAART from 1998 to 2006. Immune response was defined by CD4% > 25% and viral response as undetectable viral load on week 24. Regression models investigated predictors of response on week 24 and 144. Results 196 children were evaluated. CD4 > 25% was achieved by 54.7% of patients and undetectable viral load by 44.7% on week 24. Children with baseline CD4 15–24% had a 4 times higher chance to reach CD4 > 25% when compared to those with baseline CD4 < 15% ( P < 0.001). Female patients also experienced higher CD4% on week 24 ( P: 012) and on week 144 ( P: 0.014). Viral response on week 24 and 144 was not associated to any baseline characteristic. Improvements on CD4% was achieved mainly by patients with viral suppression. Growth parameters were similar between patients in viral failure/immune success and viral success/immune success groups ( P < 0.001). Conclusions HAART resulted in substantial increases in CD4% but viral response rates in children are highly variable. A significant proportion of treated individuals who fail to suppress virus experience CD4 T cell reconstitution. The initiation of HAART in children before severe immunessupression occurs should be considered to approach normal values of CD4 by week 24. Patients with immune response despite viral rebound have clinical disease progression rates that are similar than those with viral suppression.

Impact of HAART on growth and hospitalization rates among HIV-infected children

To evaluate HAART-associated changes in growth and hospitalization rates over time in a cohort of HIV-infected children. Children starting HAART were assessed during the first 3 years of therapy. Clinical response was assessed every 24 weeks by z scores of weight-for-age and height-for-age. Linear regression models were used to detect predictors of clinical response. Pertinent information on hospitalizations was obtained retrospectively through review of medical records. A total of 196 children were assessed. Mean weight z score increased from -1.62 (±1.32) at baseline to -1.14 (±1.12) by week 24. Mean height z score increased from -1.88 (±1.45) at baseline to -1.66 (±1.18). Better z scores at baseline were associated with greater increases in weight z scores over time. Lower viral load and higher height z scores at baseline were also associated with improved height catch-up. Eighty-five children (43.3%) were hospitalized. Most hospitalizations were prompted by infectious disease, with only two due to opportunistic infections. HAART was associated with significant increases in weight and height z scores. Younger age, the use of protease inhibitors and advanced clinical disease were associated with better outcomes. The present study demonstrated the effectiveness of HAART in significantly reducing hospitalization, death, and incidence of opportunistic infections among HIV-infected children.

Incidence of and risk factors for community acquired pneumonia in US HIV-infected children, 2000–2005

The incidence of and risk factors for community-acquired pneumonia (CAP) are described from 2000 to 2005 in a multicenter US cohort of HIV-infected children. In 736 patients, 87 episodes of CAP (33.2 events/1000 person-years) had a mean CD4% of 23% (controls: 30%) and mean CD4 cell count of 668 cells/μl (controls: 870 cells/μl). CAP incidence decreased 44% from 2000-2001 to 2002-2005. On multivariate analysis, viral load at least 100 000 copies/ml (odds ratio 3.98; confidence interval 1.05-15.13) was associated with CAP. Herd immunity through pneumococcal immunization may have diluted the effect of individual immunization in this cohort.

High Rates of Colonization with Drug Resistant Hemophilus Influenzae Type B and Streptococccus Pneumoniae in Unvaccinated HIV Infected Children from West Bengal

To determine nasopharyngeal colonization rates of two vaccine preventable bacterial pathogens Hemophilus influenzae type b (Hib), and Streptococcus pneumoniae (Pneumococcus), antibiotic susceptibility of isolates, factors associated with their colonization, and immunization history in a cohort of HIV infected children. The authors conducted a cross-sectional nasopharyngeal swab survey of 151 children affected with HIV presenting for routine outpatient care in West Bengal, India. 151 HIV affected children were enrolled. The median age was 6, 148/151 children were HIV positive, 65% had moderate to severe malnutrition, 53% were moderately to severely immunosuppressed, 17% were on antiretroviral therapy (ART), 90% were on cotrimoxazole prophylaxis (TMP/SMX). None had received the pneumococcal or Hib conjugate vaccines. Hib prevalence was 13% and pneumococcal prevalence was 28%. Children with normal or moderate immune suppression had high rates of colonization compared to those with severe immunosuppression (71% Hib, 61% pneumococcus). Hib and pneumococcal isolates had high rates of resistance to tested antibiotics including TMP/SMX and third generation cephalosporins. Neither ART nor TMP/SMX prevented colonization. Children colonized with multidrug resistant isolates had high rates of exposure to TMP/SMX. HIV infection, late access to ART, high rates of colonization to resistant organisms and lack of access to vaccines makes this population vulnerable to invasive disease from Hib and pneumococcus.

Safety and Immunogenicity of a Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) Vaccine in HIV-Infected Children 7 to 12 Years Old

Quadrivalent human papillomavirus vaccine (QHPV) is > 95% effective in preventing infection with vaccine-type human papillomavirus. The safety and immunogenicity of QHPV are unknown in HIV-infected children. HIV-infected children (N = 126)-age > 7 to < 12 years, with a CD4% ≥ 15-and on stable antiretroviral therapy if CD4% was < 25-were blindly assigned to receive a dose of QHPV or placebo (3:1 ratio) at 0, 8, and 24 weeks. Adverse events were evaluated after each dose. Serum antibody against QHPV antigens was measured by a competitive Luminex immunoassay 1 month after the third QHPV dose. The safety profile of QHPV was similar in the 2 study arms and to that previously reported for QHPV recipients. QHPV did not alter the CD4% or plasma HIV RNA. Seroconversion to all 4 antigens occurred in > 96% of QHPV recipients and in no placebo recipients. Geometric mean titer was > 27 to 262 times greater than the seropositivity cutoff value, depending on the antigen, but was 30%-50% lower against types 6 and 18 than those of age-similar historical controls. QHPV was safe and immunogenic in this cohort of HIV-infected children. Efficacy trials are warranted.

Dyslipidemia in a Cohort of HIV-infected Latin American Children Receiving Highly Active Antiretroviral Therapy

In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3-5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9-6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART.

Growth, immune and viral responses in HIV infected African children receiving highly active antiretroviral therapy: a prospective cohort study

BackgroundScale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes.MethodsA prospective cohort of HIV infected children were initiated on HAART and followed for 48 weeks. Body mass index for age z scores(BAZ), weight and height-for-age z scores (WAZ & HAZ) were calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12 weeks. Treatment outcomes were classified according to; both virological and immunological success (VS/IS), virological failure and immunological success (VF/IS). virological success and immunological failure (VS/IF) and both virological and immunological failure (VF/IF).ResultsFrom March 2004 until May 2006, 124 HIV infected children were initiated on HAART. The median age (IQR) was 5.0 years (2.1 - 7.0) and 49% (61/124) were female. The median [95% confidence interval (CI)] BAZ, WAZ and HAZ at baseline were 0.29 (-2.9, -1.2), -1.2 (-2.1, -0.5) and -2.06 (-2.9, -1.2) respectively. Baseline median CD4 cell % and log10 HIV-1 RNA were; 11.8% (7.5-18.0) and 5.6 (5.2-5.8) copies/ml. By 48 weeks, mean WAZ and HAZ in the VF/IS group, which was younger, increased from - 0.98 (SD 1.7) to + 1.22 (SD 1.2) and from -1.99 (1.7) to + 0.76 (2.4) respectively. Mean increase in WAZ and HAZ in the VS/IF group, an older group was modest, from -1.84 (1.3) to - 0.41 (1.2) and -2.25 (1.2) to -1.16 (1.3) respectively. Baseline CD4 cell % [OR 6.97 95% CI (2.6 -18.6)], age [OR 4.6 95% CI (1.14 -19.1)] and WHO clinical stage [OR 3.5 95%CI (1.05 -12.7)] were associated with successful treatment outcome.ConclusionsHIV infected Ugandan children demonstrated a robust increase in height and weight z scores during the first 48 weeks of HAART, including those who failed to completely suppress virus. Older children initiating HAART with severe immune suppression were less likely to achieve a successful treatment outcome. These data emphasize the importance of initiating HAART early to ensure adequate immune and growth responses.

HIV is associated with thrombophilia and high D-dimer in children and adolescents

Atherosclerosis and other cardiovascular diseases associated with thrombosis appear more relevant and anticipated in HIV-infected patients after combination antiretroviral therapy (cART) has reduced AIDS-related diseases and has improved survival. The association between viral replication and coagulation abnormalities in a cohort of HIV-infected children and adolescents was investigated here. Protein S, protein C anticoagulant and antithrombin activity, together with fibrinogen, D-dimer, high-sensitive C-reactive protein and homocysteine were assayed in a cross-sectional study among a cohort of HIV-infected children and adolescents. Results in patients with high viral load (HVL, HIV-RNA > 1000 copies/ml) were compared with those in patients with a lower replication (LVL), adjusting for other demographic, clinical and therapeutic covariates. Eighty-eight patients (mean age 13.5 years, CD4 30%, 72% with LVL) were enrolled. A prevalence of protein S and protein C deficiency of 51 and 8% was, respectively, found. HVL group compared to LVL showed a significant reduction of protein S, protein C and antithrombin activities, and an increase of D-dimer levels. The independent association of HVL with decreased protein S activity (-11.2%, P = 0.04) and increased D-dimer levels (+0.13 microg/ml, P = 0.004) was confirmed in the multivariate model. HIV-infected children and adolescents present high prevalence of thrombophilic abnormalities. The multivariate model confirmed that high viral replication is independently associated with decrease of protein S and increase of D-dimer, suggesting the advantage of suppressive therapy on coagulation homeostasis and the opportunity of an active control of cardiovascular risk factors starting at a younger age.

Influenza surveillance in a cohort of HIV-infected children and adolescents immunized against seasonal influenza

During the 2006–2007 season, 19 HIV-uninfected and 33 HIV-infected children and adolescents with full immunovirologic response to HAART were immunized against influenza and subsequently followed up. One month post-immunization all subjects had protective antibodies titres which persisted for the whole influenza season. Seven vaccinees (four HIV-infected and three HIV-uninfected) were found to be infected by influenza viruses during the epidemic, but disease was lab-confirmed only in two HIV-infected subjects. Both presented a benign clinical course and were infected by an A/Brisbane/10/07-H3N2-like virus. These data indicate that HIV-infected subjects benefit from routine seasonal influenza vaccination.

The changing pattern of adherence to antiretroviral therapy assessed at two time points, 12 months apart, in a cohort of HIV-infected children

Objective: In a previous multicentre study including 129 HIV-infected children, non-adherence to antiretroviral therapy was detected in 16% of patients and was mainly related to psychosocial rather than clinical or demographic features. The aim of this study was to explore the evolving pattern of adherence and its determinants in the same population of children. Methods: An observational, cross-sectional multicentre study was done through a structured interview to the caregivers of HIV-infected children. Adherence was quantitatively evaluated through a 4-day recall adherence instrument. Results: One hundred and twelve children were included. Nineteen (17%) omitted more than 5% of doses in the preceding 4 days and were considered non-adherent. Of these, 10 had been found non-adherent and nine adherent in the previous study. In parallel, nine of the originally non-adherent children had become adherent. Adherence rates were higher in children receiving therapy from foster parents than in children receiving therapy from biological parents. Dose number significantly correlated with adherence. Conclusions: Adherence to antiretroviral therapy is a dynamic phenomenon that changes with time. The evolving pattern shows a fairly constant distribution of adherence because a similar number of patients gain and lose adherence. Psychosocial rather than clinical features are major determinants of adherence.