Highly Active Antiretroviral Therapy In HIV-infected Children Research Articles

The effect of nutritional status on the response to highly active antiretroviral therapy in human immunodeficiency virus-infected children at regional antiretroviral therapy centre in Northern India

Background: Effect of highly active antiretroviral therapy (HAART) on growth in children is well established but influence of prior nutritional status on the response to HAART is not well known. Objective: To determine the influence of prior nutritional status on the response to HAART in terms of growth and CD4 counts. Methods: It was a retrospective record review based study conducted at a regional ART centre at a tertiary care, teaching hospital in Northern India. Human immunodeficiency virus (HIV) positive children who were naïve to antiretroviral therapy and were initiated on treatment from January 2006 to December 2007 were included in this study. Age, weight, height and CD4 cell counts were recorded at the initiation of HAART and after 24 months of therapy. Data was analyzed using paired t-tests within the groups, Chi-square tests, and one-way analysis of variance. Results: Seventy-nine HIV positive children were included in the study. At baseline, 29% of children were normal weight, 27% moderately underweight and 44% severely underweight with mean CD4 counts 243.30±178.50, 282.95±173.69 and 215.11±85.71 respectively. After 24 months of HAART, mean CD4 cell counts as well as weight for age z scores increased significantly in all 3 groups with mean CD4 counts being 913.61±401.46, 931.24±363.54 and 775.31±424.43 respectively in the groups. There were no significant differences in CD4 counts in the groups both pre and post ART. Conclusion: Underlying malnutrition does not adversely affect growth and immunologic response (increase in CD4 count) to HAART in HIV-infected children.

Cardiac Effects of Highly Active Antiretroviral Therapy in Perinatally HIV-Infected Children: The CHAART-2 Study

BackgroundBefore the introduction of highly active antiretroviral therapy (HAART), cardiac mortality and morbidity were common in HIV-infected children. ObjectivesThis study sought to identify long-term cardiovascular effects of HAART in HIV-infected children. MethodsThe CHAART-2 (HAART-Associated Cardiotoxicity in HIV-Infected Children) study prospectively compared 148 echocardiograms from 74 HAART-exposed children to 860 echocardiograms from 140 HAART-unexposed but HIV-infected children from the Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) study. Both studies used similar protocol, centralized echocardiographic interpretation, and measures expressed as z-scores referenced to healthy controls. Associations between HAART exposure and echocardiographic measures were evaluated using generalized estimating equations. ResultsComparing the HAART-exposed and HAART-unexposed groups, any HAART exposure was positively associated with left ventricular (LV) fractional shortening (z-score for difference = 1.07; p = 0.02) and HAART exposure duration (z-score difference per year = 0.17; p = 0.003. LV mass was negatively associated with any HAART exposure (z-score difference = −0.64; p = 0.01) as was septal thickness (z-score difference = −0.93; p = 0.001). Duration of HAART exposure was negatively associated with LV end-systolic dimension and heart rate (z-score difference per year= −0.11; p = 0.05; and z-score difference per year = −0.10; p = 0.002, respectively). During 11 years of follow-up, in the HAART-exposed group, LV mass and LV end-diastolic septal thickness were lower whereas LV contractility and LV fractional shortening were higher when compared to the HAART-unexposed group. ConclusionsCardiac structure and function were better in perinatally HIV-infected children exposed to HAART than in those of similar children from the pre-HAART era but did decline over time. Evidence-based strategies for cardiovascular monitoring are needed to inform treatment decisions to improve long-term cardiovascular health.

DYNAMICS OF CLINICAL LABORATORY PARAMETER IN HIV-INFECTED CHILDREN UNDERGOING DIFFERENT PATTERNS OF INITIAL HIGHLY ACTIVE ANTIRETROVIRAL THERAPY: RANDOMIZED CONTROLLED TRIAL

Background: Adverse course of HIV infection, rapid development of immunosuppression, severe opportunistic infections and malignant tumors and high mortality substantiate the importance of timely prescription of highly active antiretroviral therapy (HAART). The initial therapy pattern must remain efficient and safe in the long term. Objective: Our aim was to study effectiveness and safety of different patterns of initial HAART in HIV-infected children. Methods: The randomized controlled trial involved HIV-infected children aged 1–3 years. Clinical, immunological and virological examinations were conducted before and 12 months after HAART. The initial therapy pattern included 2 nucleoside HIV reverse transcriptase inhibitors — zidovudine and lamivudine. Children were randomized to the groups differing in the third therapy component: lopinavir/ritonavir or nevirapine. Results: 25 patients were randomized to the lopinavir/ritonavir group, 23 children — to the nevirapine group. After 12 months of treatment, HIV replication suppression (blood viral load < 50 copies/ml) was achieved in 25 (100%) lopinavir/ritonavir group patients and in 16 (70%) nevirapine group patients (p = 0.003). HIV infection did not progress clinically regardless of the pattern. The median number of CD4+CD3+ lymphocytes in the lopinavir/ritonavir group increased from 20.5% (12; 23) to 30% (27; 34) (p < 0,001), in the nevirapine group — from 21.5% (17; 23) to 29% (27; 38) (p < 0.001). Adverse events developed in 13 (27%) children. 3 and 2 children in the lopinavir/ritonavir group suffered from nausea and emesis, respectively. 1 and 1 patient in the nevirapine group suffered from allergic rash and drug-induced hepatitis, respectively. Conclusion: High effectiveness and safety of lopinavir/ritonavir allow recommending this drug as the third component of the initial HAART pattern for HIV-infected children.

Outcome of highly active antiretroviral therapy in HIV-infected Indian children.

BackgroundWith the advent of highly active antiretroviral therapy (HAART), HIV infection has become a chronic condition in children with improved survival and quality of life. Reports on long term effectiveness of non-nucleoside reverse transcriptase inhibitor based HAART in HIV-infected children in developing countries are limited.MethodsA chart review was conducted and children who received at least six months of HAART between 2004–2011 at All India Institute of Medical Sciences (AIIMS), Delhi were included. The clinical, immunological and virological responses to HAART were documented. Factors predicting non-adherence and non-response to treatment were described.ResultsOne seventy five children (boys: 74.9%) were included in the study, with a median follow up of 43 (IQR:17, 68) months. The median age at diagnosis was 119 (IQR: 75, 156) months. The median CD4 count at start of HAART was 340 cells/μL (IQR: 185,704), which increased to 924 cells/μL (IQR:591,1278) at 48 months after HAART and plateaued at 749 (IQR: 542,1056) cells/ μL after 90 months of therapy. The weight for age (WAZ) and height for age (HAZ) z score both showed improvement with time after HAART initiation [baseline: WAZ −2.8 (IQR:-4,-1.6), HAZ −2.1 (IQR:-3.4,-0.69); at 42 months of therapy: WAZ −1.2 (IQR:-2.1, 0.01), HAZ −0.75(IQR:-1.6,-0.37)]. Adverse events were reported in 21 (12%) children. Non-adherence to therapy, treatment failure and death were noted in 35 (20%), 9 (5.1%) and 6 (3.4%) children respectively.ConclusionsOur experience shows that HAART in HIV-infected children is effective, safe and is associated with good immunological and virological response as well as improvement in growth parameters.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0701-2) contains supplementary material, which is available to authorized users.

Opportunistic and Other Infections in HIV-Infected Children in Latin America Compared to a Similar Cohort in the United States

Opportunistic and other infections have declined since the introduction of highly active antiretroviral therapy (HAART) in developed countries but few studies have addressed the impact of HAART in HIV-infected children from developing countries. This study examines the prevalence and incidence of opportunistic and other infections in Latin America during the HAART era. Vertically HIV-infected children enrolled in a cohort study between 2002 and 2007 were followed for the occurrence of 29 targeted infections. Cross-sectional and longitudinal analyses were performed to calculate the prevalence of infections before enrollment and the incidence rates of opportunistic and other infections after enrollment. Comparisons were made with data from a U.S. cohort (PACTG 219C). Of the 731 vertically HIV-infected children 568 (78%) had at least one opportunistic or other infection prior to enrollment. The most prevalent infections were bacterial pneumonia, oral candidiasis, varicella, tuberculosis, herpes zoster, and Pneumocystis jiroveci pneumonia. After enrollment, the overall incidence was 23.5 per 100 person-years; the most common infections (per 100 person-years) were bacterial pneumonia (7.8), varicella (3.0), dermatophyte infections (2.9), herpes simplex (2.5), and herpes zoster (1.8). All of these incidence rates were higher than those reported in PACTG 219C. The types and relative distribution of infections among HIV-infected children in Latin America in this study are similar to those seen in the United States but the incidence rates are higher. Further research is necessary to determine the reasons for these higher rates.

Article Commentary: Treating an HIV-Infected Paediatric Patient: An Easy Task?

HIV-infected children represent an incredibly diverse group of patients, ranging from neonates to young adults. With the change in age and maturity, paediatric highly active antiretroviral therapy (HAART) evolves from the meticulous twice-daily dosing of ml of liquid preparations to a choice of once-daily dosing of a single fixed-dose coformulated tablet. The use of simplified paediatric regimens could enhance the ability to achieve successful implementation of HAART in HIV-infected children. Pharmacokinetics and pharmacodynamic studies of antiretroviral drugs and their combinations need to be conducted in infants, children and adolescents to develop appropriate dosing in each of these specific groups.

Safety, Tolerability and Effectiveness of Generic HAART in HIV-Infected Children in South India

HIV-infected children in resource-limited settings are increasingly gaining greater access to highly active antiretroviral therapy (HAART) but documented longitudinal data remains limited. We aimed to study the clinical and immunological outcomes among 67 South Indian HIV-infected children with >18 months of follow-up on HAART at a tertiary HIV care program. The median CD4 cell count at enrolment was 290 cells microl(-1) and at treatment initiation was 225 cells microl(-1). Patients demonstrated a significant rise in their CD4 cell counts between treatment initiation and after 6 months (701 cells microll(-1); p = 0.007), 12 months (741 cells microl(-1); p = 0.037), and 18 months of therapy (718 cells microl(-1); p = 0.005). The most common adverse events to therapy were nausea (20.9%) and rash (25.4%). Over one-fifth of patients (25.4%) substituted therapy due to toxicities and 19.4% of patients switched to second-line protease inhibitor-containing regimens. In this South Indian pediatric cohort, generic HAART was safe, effective and relatively well tolerated.

Impact on Weight and Height With the Use of HAART in HIV-Infected Children

There are few data on long-term effects of highly active antiretroviral therapy (HAART) on weight and height in HIV-infected children. Our objective was to assess the effect of HAART on the weight and height of HIV-infected children over time in the Madrid cohort, and analyze possible factors associated with the effect. This was a retrospective study of HIV-infected children starting HAART in 1997 or later. Serial measurements of weight, height and body mass index (BMI) were performed and converted to z-scores using the Spanish revised reference data. Changes from baseline in weight, height and BMI at 12, 24, 36, 48 and 60 months were determined. Associations of z-scores at the last visit with immunologic (CD4% above 25%) and virologic responses (more than 50% of samples below 400 copies/mL), CDC (Centers for Disease Control) clinical category, and the presence and type of lipodystrophy (lipoatrophy or lipohypertrophy) were evaluated. Twelve hundred and twelve children, 97% of them vertically-infected, received HAART starting in 1997 for a median of 71 months (4-102 months). Median age at initiation of HAART was 6 years (1 month-18 years). Thirty-nine percentage were antiretroviral naive and 61% had received NRTI therapy previously. Thirty-two percentage and 53% had CDC class C and immunologic class 3, respectively. At the final evaluation, 24% of children remained on their first combination therapy, 39% on the second and 37% had received at least 3 different HAART regimens. Fifty-one percentage were classified as virologic responders. Thirty-nine percentage of children in this study were diagnosed with lipodystrophy. At baseline, median z-score for weight, height and BMI were -0.45, -0.60 and -0.33, respectively. HAART was associated with significant increases in z-scores of weight and height but not BMI at the different time-points analyzed. Virologic nonresponders had significantly lower z-scores for weight and height but not for BMI. CDC class C was associated with lower z-scores for height. No differences in final measurements were observed for baseline CD4, immunologic response or lipoatrophy. Children with lipohypertophy had a significantly higher BMI at the last visit. HIV-infected children experienced a continued catch-up in weight and height 5 years after starting HAART. Virologic control is related to sustained growth.

Coercive Treatment of HIV-Positive Children Is Not Justified: In Reply

ARTICLEIn Reply.— It is our responsibility as pediatric health care providers to promote the health and well-being of the children who present to us for care. We respectfully disagree with Crowe et al that, “[t]here is simply no firm evidence that children will live longer when medicated earlier with AIDS drugs.” On the contrary, there is ample evidence that highly active antiretroviral therapy (HAART) has had tremendous effects on improving morbidity profiles, reducing mortality rates, and delaying death among HIV-infected children.1,2 Regarding infants in particular, analyses from a large prospective study of 360 HIV-infected US children (Perinatal AIDS Collaborative Transmission Study) showed that infants who received early treatment with HAART were significantly less likely to progress to AIDS or death compared with those who received no therapy, adjusting for year of birth and maternal disease factors.3 The increased potency of regimens containing protease inhibitor (PI) drugs has resulted in enhanced survival of HIV-infected children and a reduction in opportunistic infections and other complications of HIV infection as demonstrated in a prospective longitudinal cohort study (Perinatal AIDS Collaborative Transmission Group, PACTG 219),4 which started enrollment before the availability of PI therapy. The increased use of PI-containing therapy (from 0% before 1996 to >70% by 1998) was accompanied by a substantial decrease in mortality: mortality decreased from 5% in 1995/1996 to only 1% in 1997/1998. Similar reductions in mortality with introduction of HAART in HIV-infected children in Europe have also been reported.2,5,6 Crowe et al suggest that because children face a greater number of years on therapy than adults, a rational approach is to delay the initiation of therapy as long as possible. We agree with this approach as long as the child's clinical, immunologic, or HIV RNA status does not …

HIV-infected children with moderate/severe immune-suppression: changes in the immune system after highly active antiretroviral therapy.

The objective of this study was to monitor the changes in the immune system of HIV-infected children with moderate or severe immunodeficiency after highly active antiretroviral therapy (HAART), comprising a follow-up study in 14 HIV-infected children on HAART at two time points separated approximately by 11.8 +/- 0.4 (9.9; 15.4) months. HIV-infected children had significantly lower TREC levels than the control group, but 1 year after HAART the levels increased significantly (P < 0.05). In contrast, viral load (VL) did not change significantly. A positive correlation between T cell receptor excision circle (TREC) levels and both CD4(+) T cell absolute counts (r = 0.558; P = 0.05) and percentages (r = 0.625; P = 0.030) was found. During follow-up on HAART, the percentages and absolute counts of naive CD4(+) and CD8(+) T cell subsets were increased significantly (P < 0.05). CD4(+) CD45RA(hi+) CD62L(+), CD4(+) CD45RA(+) and CD4(+) CD38(+) percentages, and the CD8(+) CD45RA(hi+) CD62L(+) counts reached similar values to the control group. Also, CD8(+) CD45RO(+) CD38(+) and CD8(+) CD45RO(+) percentages, and CD8(+) CD45RO(+) CD38(+) absolute counts (P < 0.05) decreased with respect to the baseline. Lymphoproliferative responses to pokeweed mitogen (PWM) before HAART were lower in HIV-infected children than the control group, but they recovered to normal levels after a year on HAART. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma production by PHA-activated peripheral blood mononuclear cells (PBMC) was lower before HAART (P < 0.001), but reached similar levels to the control group 1 year after HAART. In HIV-infected children IgG, IgG(1) and IgG(3) plasma levels decreased significantly after HAART. The immune system reconstitution induced by HAART in HIV-infected children seems to be the consequence of decreased immune system activation and naive T cell reconstitution, mainly of thymic origin.

Highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children: analysis of cellular immune responses.

The present study analyzes the effect of highly active antiretroviral therapy (HAART) on restoration of cellular immunity in human immunodeficiency virus (HIV)-infected children over a 24-week period following initiation of HAART with ritonavir, nevirapine, and stavudine. The immunological parameters evaluated at four time points (at enrollment and at 4, 12, and 24 weeks of therapy) included cytokine production by monocytes as well as T-cell proliferation in response to mitogen, alloantigen, and recall antigens including HIV type 1 envelope peptides. Circulating levels of interleukin-16 (IL-16) were measured, in addition to CD4+ T-cell counts, plasma HIV RNA levels, and the delayed-type hypersensitivity (DTH) response. At enrollment the children exhibited defects in several immune parameters measured. Therapy increased CD4+ T-cell counts and decreased viral loads significantly. By contrast, the only immunological parameter that was significantly increased was IL-12 p70 production by monocytes; the DTH response to Candida albicans also showed a strong increase in patients becoming positive. In conclusion, these results demonstrate that HAART in HIV-infected children affects the dynamics of HIV replication and the CD4+ T-cell count over 24 weeks, similar to the pattern seen in HIV-infected adults. Furthermore, these data indicate improvement in antigen-presenting cell immunological function in HIV-infected children induced by HAART.

Gastrostomy tube insertion for improvement of adherence to highly active antiretroviral therapy in pediatric patients with human immunodeficiency virus.

Newer combination antiretroviral therapies used to treat human immunodeficiency virus (HIV)-infected individuals have resulted in dramatic delays in HIV progression, with reduction in mortality and morbidity. However, adherence to highly active antiretroviral therapy (HAART) may be problematic, particularly in HIV-infected children. Reasons for nonadherence include refusal, drug tolerability, and adverse reactions. We assess: 1) the potential benefits of gastrostomy tube (GT) for the improvement of adherence to HAART in HIV-infected children, and 2) the factors that may result in improved viral suppression after GT placement. The medical records of 17 pediatric HIV-infected patients, in whom GT was used to improve HAART adherence, were retrospectively reviewed for clinical and laboratory parameters. Each record was reviewed for the period of 1 year before and after GT insertion. The main outcome parameters were virologic (plasma HIV RNA polymerase chain reaction quantification) and immunologic (CD4 cell counts). Documentation of adherence to medications in medical records was also assessed during the study. Parental questionnaires were used to determine GT satisfaction and medication administration times. The Wilcoxon rank sum test was used to assess change in viral load (VL) and CD4 cell percentages. GT was well-tolerated with minor complications, such as local site tenderness, reported by 4 patients (23%). Before GT insertion, only 6 patients (35%) were documented as being adherent, compared with all patients after GT insertion. Ten patients (58%) had >/=2 log(10) VL decline after GT insertion (median: 3.2 log(10)), compared with 7 patients (42%) who had </=2 log(10) VL decline (median: 1.27 log(10)). Both groups of patients (responders and nonresponders) did not differ significantly in baseline parameters, such as VL, CD4 cell percentages, or previous drug therapy. However, in all 10 patients with >/=2 log(10) VL decline, therapy was changed at the time of or soon after GT insertion (median:.8 months; range: 0-6 months), compared with 7 patients with <2 log(10) VL decline who had therapy changed before GT insertion (median: 3.2 months; range: 1-8 months). Parental questionnaires reported significantly shorter medication administration times after GT insertion, with 70% of patients taking >5 minutes before GT, compared with 0% after GT. Questionnaires indicated satisfaction with GT, with perceived benefits being reduced medication administration time and improved behavior surrounding taking medications. GT is well-tolerated in pediatric HIV-infected patients and should be considered for selected patients to overcome difficulties with medication administration and to improve adherence. For maximal virologic response, combination therapy should be changed at the time of GT insertion.