The impact of highly active antiretroviral therapy on the burden of bacterial lower respiratory tract infections in children

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Abstract

BACKGROUND: Respiratory diseases are common and associated with significant morbidity and mortality in children. OBJECTIVE: To evaluate the prevalence and outcome of bacterial lower respiratory tract infections (LRTIs) in HIV-infected and uninfected children at a primary level hospital. METHODS: A cross-sectional descriptive study of children aged 6 months - 18 years was conducted. Recruitment included HIV-positive children who had been on highly active antiretroviral therapy (HAART) for at least 6 months. A comparator group of HIV-negative children admitted with bacterial pneumonia was included. Laboratory data collected included CD4+ T-cell counts, HIV viral load and C-reactive protein (CRP). Data collected in both groups included demographic data, immunisation status, zinc supplementation, previous LRTIs, environmental exposures and treatment. RESULTS: Fifty-nine HIV-infected and 20 uninfected children were enrolled. The HIV-positive children were older, with a mean age of 107.2 (standard deviation 50.0) months v. 12.0 (5.8) months (p<0.005). The HIV-infected group had a mean CD4 percentage of 31.5%, and had had an average of 3.9 visits for bacterial LRTIs. All were treated with amoxicillin with no complications. In the HIV-uninfected group, cough and rapid breathing were the most common presenting symptoms, and the mean CRP level was 463.0 mg/L. The mean hospital stay was 4 days. CONCLUSION: HAART is effective in reducing the burden of LRTIs in HIV-positive children, even when the diagnosis is delayed. Cough and fast breathing are still the most reliable presenting symptoms of pneumonia. The majority of children still respond to amoxicillin as first-line therapy, with low complication rates.

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Community-acquired pneumonia in HIV-infected children: a global perspective.

H Zar, Neil D. Gray (2010)

Pneumonia is a leading cause of morbidity and death in HIV-infected children. The aim of this study was to review recent advances in the epidemiology, cause, management and prevention of pneumonia in HIV-infected children. Pneumonia remains a major cause of death and hospitalization, particularly in sub-Saharan Africa, where the paediatric HIV epidemic is concentrated. HIV-infected children have a higher risk of developing pneumonia and of more severe disease than immunocompetent children. Bacterial pathogens especially Streptococcus pneumoniae, Staphylococcus aureus and Gram-negative bacteria predominate, with rising rates of antimicrobial resistance. Mycobacterium tuberculosis is increasingly reported to cause acute pneumonia. Pneumocystis jirovecii (PCP) remains an important cause of severe pneumonia especially in infants. Viral infections, especially cytomegalovirus-associated pneumonia are common. Polymicrobial infection is increasingly recognized and associated with a worse prognosis. HIV-exposed, negative children have an increased risk of infection with opportunistic pathogens and a poorer outcome than HIV-unexposed children.Increasing access to highly active antiretroviral therapy (HAART) has reduced the incidence of severe pneumonia, eliminated most opportunistic infections and improved outcome. However, pneumonia remains the major cause of morbidity in HIV-infected children taking HAART. Standard case management guidelines are effective at decreasing mortality but require adaptation for high HIV-prevalence areas. Broad-spectrum antibiotics should be used as empiric therapy. Infants or children who are not taking pneumocystis prophylaxis should be treated for PCP.A number of general or specific preventive strategies are effective including early use of HAART at the time of HIV diagnosis, pathogen-specific immunizations, in particular pneumococcal conjugate vaccine, and antibiotic prophylaxis against PCP. Greater access to preventive and treatment strategies, especially PCP prophylaxis, pneumococcal immunization and HAART, are urgently needed in areas of high childhood HIV prevalence.

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Impact of highly active antiretroviral therapy on the morbidity and mortality in Spanish human immunodeficiency virus-infected children.

Jose Sanchez, Pablo Conejo, J R Vivas … (2003)

Highly active antiretroviral therapy (HAART) slows the progression of HIV disease and lowers mortality and morbidity in adults. The impact on the disease course in children has not been still completely elucidated. Furthermore the effect of HAART on organ-specific complications of HIV is unknown. To assess the effect of HAART on the progression of HIV infection, mortality, organ-specific complications, number of infections and hospitalizations in HIV-1-infected children. Records of HIV-1-infected children were reviewed in a large referral pediatric hospital. Patients were divided into three groups: children who did not receive antiretroviral therapy (Group 1); children who received mono- or bitherapy (Group 2); and patients who received HAART (Group 3). Endpoints analyzed were progression to AIDS and mortality among AIDS patients and overall. One hundred seven children have been evaluated. Actuarial survival at 5 years of age was 33% in Groups 1 and 2 compared with 100% in Group 3 (P < 0.01). At 5 years of age, the proportion of children progressing to AIDS was 76% in Groups 1 and 2, compared with 26% in Group 3 (P < 0.01). At 5 years of follow-up, there were 45 cases of organ-specific complications in patients without HAART. No children without organ-specific complications when HAART was started have developed them after 5 years (P < 0.01). In patients without HAART there were 9 cases of lymphoid interstitial pneumonia, and there was none in Group 3 (P < 0.01). The incidence rates of infections and hospitalizations were 2.83 and 0.52 per patient-year, respectively, in children who did not receive HAART and 0.75 and 0.17 when they were managed with HAART (relative risk, 0.26 and 0.32). HAART is associated with a marked decline in the progression to AIDS, improved survival in HIV-1-infected children, reduced incidence of infections and hospitalizations and decreased incidence of some organ-specific complications of HIV.