Decreased needs for hospital care and antibiotics in children with advanced HIV-1 disease after protease inhibitor-containing combination therapy

Abstract

Protease inhibitor-containing antiretroviral combination therapy is being increasingly used for treating children with symptomatic HIV infection [^1,2]. It is expected to modify the natural history of the disease and to have a major impact on the needs for health care. There is also increasing concern regarding the financial needs related to HIV infection because of the high costs of combination therapy.

The need for medical care increases with the progressive severity of the disease [³]. However, it is possible that the costs of combination therapy may be balanced by the reduced needs for medical care as a consequence of combination therapy itself.

A pilot study was started to investigate the impact of combination therapy on the rate of hospitalization and the duration of antibiotic administration in children with HIV infection shifted to protease inhibitor-containing combination therapy. In December 1997, 10 patients (five boys, average age 7.6 years, range 5-14 years) seen at our tertiary care centre for paediatric HIV infection, were started on triple therapy with two reverse transcriptase inhibitors (five, stavudine plus lamivudine; three, zidovudine plus lamivudine; two, stavudine plus didanosine) plus the protease inhibitor ritonavir. All children were in immunological class 3 (severely immunosuppressed); six were in clinical class C (severely symptomatic) and four were in class B (moderately symptomatic) of the Centers for Disease Control and Prevention 1994 classification system [⁴]. All children had previously received reverse transcriptase inhibitors either alone or in combination, and were naive for treatment with protease inhibitors.

A sustained decrease of HIV-1 plasma RNA copy number, which fell below the level of detection in six children (median decrease 3.49 log10, range -2.5 to -3.6 log10; P = 0.001), associated with a marked increase in CD4 cell counts (median increase 778 cells/mm3, range 478-840 cells/mm3; P = 0.001) was observed in all patients. Combination therapy was well tolerated, with no major adverse effects. While on combination therapy, no further AIDS-defining clinical events or opportunistic infections were observed in the six children already classified as C. None of the four children who were included in class B at enrolment showed evidence of progression of HIV infection. In comparison, in the 12 months before the start of combination therapy, a total of five AIDS-defining events had been recorded in the same 10 children, including two episodes of oesophageal candidiasis, one disseminated atypical mycobacteriosis, one pulmonary tuberculosis, and one non-Hodgkin‚s lymphoma, respectively. In addition, several episodes of HIV-associated diseases, mainly bacterial pneumonia, had required hospital admissions.

The rate of hospital admissions was dramatically reduced after the start of combination therapy (Table 1). Overall, clinical improvement allowed a significant reduction in day hospital admissions (Table 1). The clinical records of the 10 children were examined to obtain the total number of days on which each child had received antibiotic treatment in the 12 months before and the 12 months after the start of combination therapy. The prophylactic use of antibiotics was not taken into account. After the start of combination therapy the time of antibiotic treatment was reduced by two-thirds (Table 1).

Table 1: Need for hospitalizations and antibiotic therapy in HIV-infected children in the year before and after ritonavir combination therapy

The results of this pilot study, even though obtained in a limited sample size, strongly support the concept that combination therapy with protease and reverse transcriptase inhibitors is highly active against HIV, and capable of modifying the natural history of the disease in children. The dramatic reduction in the hospitalization rate observed in the same children after ritonavir combination therapy is compelling proof of the beneficial impact of this treatment on both the quality of life and on the costs of healthcare for children with advanced HIV disease. The even more impressive reduction in antibiotic administration supports the efficacy of this treatment and gives an idea of its economic impact, similar to that observed in adults [⁵]. In the current scenario of the HIV epidemic, a best approach towards the treatment of HIV-infected children is called for.