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ART Reduces Opportunistic Illnesses in Children and Adults with HIV


A pair of comprehensive reviews supported by the World Health Organization (WHO) have found that prompt initiation of antiretroviral therapy (ART) is associated with a lower risk of developing opportunistic infections and other HIV-related illnesses in children and adults living with HIV. Both reviews were published in the June 15 edition of Clinical Infectious Diseases.

UNAIDS estimates that approximately 37 million people are living with HIV worldwide. Of these, an estimated 2.6 million are children under the age of 15, most of whom live in sub-Saharan Africa. UNAIDS recently reported that 17 million people with HIV were receiving antiretroviral treatment at the end of 2015.

It is well known that effective treatment suppresses HIV replication, allowing the immune system to recover. ART has led to a dramatic reductions in rates of opportunistic infections (OIs) and mortality, but this decline has not been fully quantified, especially in low- and middle-countries.

Studies of Children

For the first report, Marie-Renee B-Lajoie from McGill University and colleagues did a systematic review and meta-analysis to evaluate the incidence (new cases) and prevalence (all existing cases) of 14 OIs and other infections, as well as the impact of ART, among HIV-infected children under age 18 in Africa, Asia, and Latin America.

The researchers searched databases including Medline, Global Health, Embase, Web of Knowledge, and Literatura Latino Americana em Ciências da Saúde for relevant studies published between January 1990 and November 2013 that reported incidence or prevalence of common HIV-related OIs in children. They identified 88 eligible studies, each of which included at least 50 participants, for a combined total population of 55,679 HIV-infected children.

Bacterial pneumonia and pulmonary tuberculosis were the most common incident infections in both ART-naive and ART-exposed children (25% and 22% for pneumonia; 10% and 9% for TB). Among the 60 studies that reported prevalence data, bacterial pneumonia was again most common, followed by oral/esophageal candidiasis (thrush) and sepsis.

Use of ART led to a significant reduction in incidence rates for a majority of OIs, with a smaller impact on bacterial sepsis and pneumonia, and an actual increase for herpes zoster (shingles). ART had the most dramatic effect -- more than an 80% reduction -- on incidence of cryptosporidial diarrhea, toxoplasmosis, and TB.

The study authors calculated that starting ART based on 2010 WHO guidelines -- which did not yet call for universal treatment but were based on CD4 percentage and cell count -- potentially averted more than 161,000 OIs, with a cost savings of around $17 million per year, with most of the savings attributable to reduction of TB.

"There is a decrease in the risk of most OIs with ART use in HIV-infected children in [lower- and middle-income countries], and estimated large potential cost savings in OIs averted with ART use, although there are greater uncertainties in pediatric data compared with that of adults," the authors concluded.

Studies of Adults

As described in the second report, Andrea Low from Columbia University's Mailman School of Public Health and colleagues conducted a systematic review and meta-analysis to evaluate the effect of ART on incidence of key OIs among HIV-positive adults in low- and middle-income countries.

This analysis used multiple databases to identify 126 eligible studies describing cumulative OI incidence and the proportion of patients on ART between 1990 and 2013, with a total of 491,608 adult participants.

Oral candidiasis, TB, herpes zoster, and bacterial pneumonia were the most common OIs in ART-untreated adults. Reductions in OI incidence were greatest during the first 12 months after starting treatment (ranging from 57%-91%), with the exception of TB. Oral candidiasis, Pneumocystis pneumonia, and toxoplasmosis had the largest decreases.

The researchers estimated that starting ART earlier, before an individual's CD4 count fell below 200 cells/mm3, averted more than 857,800 cases of OIs in 2013, with cost savings of nearly $47 million.

"There was a major reduction in risk for most OIs with ART use in [lower- and middle-income countries], with the greatest effect seen in the first year of treatment," the authors concluded. "ART has resulted in substantial cost savings from OIs averted."

"We know that ART has a dramatic effect in reducing death rates as well as new HIV infections. These findings demonstrate that ART has the same effect in reducing the risk of serious HIV-related infections in adults and children,"WHO HIV director Gottfried Hirnschall said in aWHO press release. "This reinforces the need to continually prioritize the expansion of access to ART. The new WHO guidelines recommend starting ART in all HIV-infected persons as soon as possible, regardless of the stage of infection."



MR B-Lajoie, O Drouin, G Bartlett, et al. Incidence and Prevalence of Opportunistic and Other Infections and the Impact of Antiretroviral Therapy Among HIV-infected Children in Low- and Middle-income Countries: A Systematic Review and Meta-analysis. Clinical Infectious Diseases. 62(12):1586-1594. June 15, 2016.

A Low, G Gavriilidis, N Larke, et al. Incidence of Opportunistic Infections and the Impact of Antiretroviral Therapy Among HIV-Infected Adults in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis. Clinical Infectious Diseases 62(12):1595-1603. June 15, 2016.

Other Source

World Health Organization. WHO Confirms Antiretroviral Therapy Reduces the Risk of Life-Threatening HIV-Related Infections. Press release. June 20, 2016.