Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

Cytomegalovirus

Last Updated: November 6, 2013; Last Reviewed: November 6, 2013

Panel's Recommendations for Cytomegalovirus
Panel's Recommendations

Cytomegalovirus (CMV) antibody testing is recommended at age 1 year and then annually for CMV-seronegative, HIV-infected infants and children who are immunosuppressed (i.e., CD4 T-lymphocyte (CD4) cell count <100 cells/mm3 or CD4 percentage <10%) (BII).

HIV-infected children aged <5 years who are CMV-infected and severely immunosuppressed (i.e., CD4 cell count <50 cells/mm3 or CD4 percentage <5%) should have a dilated retinal examination performed by an ophthalmologist every 6 months (AIII).

CMV end-organ disease is best prevented by antiretroviral therapy (ART) to maintain the CD4 cell count >100 cells/mm3 in children aged ≥6 years, or CD4 percentage >10% in children <6 years (BIII). Prophylaxis with valganciclovir can be considered for HIV-infected children aged ≥6 years who are CMV-seropositive and have CD4 cell counts <50 cells/mm3 and for HIV-infected children aged <6 years who are CMV-seropositive and have a CD4 percentage <5% (CIII). Cessation of primary prophylaxis can be considered when the CD4 cell count is >100 cells/mm3 for children ≥6 years of age, or >10% in children <6 years (CIII).

Intravenous (IV) ganciclovir therapy (6 mg/kg/dose administered every 12 hours) for 6 weeks can be considered for HIV-exposed or HIV-infected infants who have symptomatic congenital CMV disease involving the central nervous system (CNS) (BI).

For HIV-infected infants and children, IV ganciclovir is the drug of choice for initial treatment for acquired CMV disease, including retinitis and other end-organ disseminated CMV disease (e.g., colitis, esophagitis, CNS disease) (AI*). Oral valganciclovir has not been evaluated in HIV-infected children with CMV retinitis, but is an option primarily for older children who weigh enough to receive the adult dose and formulation of valganciclovir (CIII). Transition from IV ganciclovir to valganciclovir oral solution can be considered for younger patients who improve on IV therapy (CIII).

Foscarnet is an alternative drug for treating CMV disease or for use in ganciclovir-resistant CMV infections in HIV-infected children (AI*).

Combination therapy with ganciclovir and foscarnet delays progression of retinitis in certain patients in whom monotherapy fails and can be used as initial therapy in children with sight-threatening disease (BIII).

Combination treatment with IV ganciclovir and foscarnet may be preferable as initial therapy to stabilize CMV neurologic disease and maximize response (BII*).

Many experts would initially treat early first relapse of retinitis with reinduction using the same drug, followed by reinstitution of maintenance therapy (AII*). If drug resistance is suspected, change to an alternative drug is reasonable (AIII). Combination IV ganciclovir and foscarnet can be considered.

After induction therapy, secondary prophylaxis (chronic maintenance therapy) is given for most forms of CMV disease until immune reconstitution or, in absence of immune reconstitution, for the remainder of a patient’s life (AI*). Regimens recommended for chronic suppression include IV ganciclovir, oral valganciclovir, IV foscarnet, combined IV ganciclovir and foscarnet, and parenteral cidofovir (AI*)
Chronic maintenance therapy is not routinely recommended for gastrointestinal disease but should be considered if relapses occur (BII*). A role for maintenance therapy for CMV pneumonitis has not been established (CIII).

Discontinuing secondary prophylaxis may be considered for children who are receiving ART and have a sustained (such as >6 months) increase in CD4 cell count, defined as an increase in CD4 percentage to >15% for children aged <6 years, or an increase in CD4 cell count to >100 cells/mm3 for children aged ≥6 years (CIII).

All patients with CMV ophthalmic disease in whom anti-CMV maintenance therapy has been discontinued should continue to undergo regular ophthalmologic monitoring at 3- to 6-month intervals for early detection of CMV relapse and for immune reconstitution uveitis (AII*).

Secondary prophylaxis should be reinstituted in HIV-infected children in whom it was discontinued because of immune reconstitution when the CD4 percentage decreases to <15% in those aged <6 years and when the CD4 cell count decreases to <100 cells/mm3 in those aged ≥6 years (BIII).

Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials in children with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion

Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents

Panel's Recommendations for Cytomegalovirus
Panel's Recommendations

Cytomegalovirus (CMV) antibody testing is recommended at age 1 year and then annually for CMV-seronegative, HIV-infected infants and children who are immunosuppressed (i.e., CD4 T-lymphocyte (CD4) cell count <100 cells/mm3 or CD4 percentage <10%) (BII).

HIV-infected children aged <5 years who are CMV-infected and severely immunosuppressed (i.e., CD4 cell count <50 cells/mm3 or CD4 percentage <5%) should have a dilated retinal examination performed by an ophthalmologist every 6 months (AIII).

CMV end-organ disease is best prevented by antiretroviral therapy (ART) to maintain the CD4 cell count >100 cells/mm3 in children aged ≥6 years, or CD4 percentage >10% in children <6 years (BIII). Prophylaxis with valganciclovir can be considered for HIV-infected children aged ≥6 years who are CMV-seropositive and have CD4 cell counts <50 cells/mm3 and for HIV-infected children aged <6 years who are CMV-seropositive and have a CD4 percentage <5% (CIII). Cessation of primary prophylaxis can be considered when the CD4 cell count is >100 cells/mm3 for children ≥6 years of age, or >10% in children <6 years (CIII).

Intravenous (IV) ganciclovir therapy (6 mg/kg/dose administered every 12 hours) for 6 weeks can be considered for HIV-exposed or HIV-infected infants who have symptomatic congenital CMV disease involving the central nervous system (CNS) (BI).

For HIV-infected infants and children, IV ganciclovir is the drug of choice for initial treatment for acquired CMV disease, including retinitis and other end-organ disseminated CMV disease (e.g., colitis, esophagitis, CNS disease) (AI*). Oral valganciclovir has not been evaluated in HIV-infected children with CMV retinitis, but is an option primarily for older children who weigh enough to receive the adult dose and formulation of valganciclovir (CIII). Transition from IV ganciclovir to valganciclovir oral solution can be considered for younger patients who improve on IV therapy (CIII).

Foscarnet is an alternative drug for treating CMV disease or for use in ganciclovir-resistant CMV infections in HIV-infected children (AI*).

Combination therapy with ganciclovir and foscarnet delays progression of retinitis in certain patients in whom monotherapy fails and can be used as initial therapy in children with sight-threatening disease (BIII).

Combination treatment with IV ganciclovir and foscarnet may be preferable as initial therapy to stabilize CMV neurologic disease and maximize response (BII*).

Many experts would initially treat early first relapse of retinitis with reinduction using the same drug, followed by reinstitution of maintenance therapy (AII*). If drug resistance is suspected, change to an alternative drug is reasonable (AIII). Combination IV ganciclovir and foscarnet can be considered.

After induction therapy, secondary prophylaxis (chronic maintenance therapy) is given for most forms of CMV disease until immune reconstitution or, in absence of immune reconstitution, for the remainder of a patient’s life (AI*). Regimens recommended for chronic suppression include IV ganciclovir, oral valganciclovir, IV foscarnet, combined IV ganciclovir and foscarnet, and parenteral cidofovir (AI*)
Chronic maintenance therapy is not routinely recommended for gastrointestinal disease but should be considered if relapses occur (BII*). A role for maintenance therapy for CMV pneumonitis has not been established (CIII).

Discontinuing secondary prophylaxis may be considered for children who are receiving ART and have a sustained (such as >6 months) increase in CD4 cell count, defined as an increase in CD4 percentage to >15% for children aged <6 years, or an increase in CD4 cell count to >100 cells/mm3 for children aged ≥6 years (CIII).

All patients with CMV ophthalmic disease in whom anti-CMV maintenance therapy has been discontinued should continue to undergo regular ophthalmologic monitoring at 3- to 6-month intervals for early detection of CMV relapse and for immune reconstitution uveitis (AII*).

Secondary prophylaxis should be reinstituted in HIV-infected children in whom it was discontinued because of immune reconstitution when the CD4 percentage decreases to <15% in those aged <6 years and when the CD4 cell count decreases to <100 cells/mm3 in those aged ≥6 years (BIII).

Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials in children with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion

Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents

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