Correspondence
Infants with CMV and HIV-1
N Engl J Med 1999; 341:1476-1477November 4, 1999
- Article
To the Editor:
The report by Kovacs et al. (July 8 issue)1 on acceleration of human immunodeficiency virus type 1 (HIV-1) disease progression in cytomegalovirus (CMV)–infected children prompts several questions. What were the relative contributions of HIV-1 and CMV to the increased neurologic morbidity in this observational study? It is well established that both viruses may lead to impaired brain growth and progressive motor deficits. In contrast to immunocompetent infants, those who are also infected with HIV-1 may be at an increased risk for CMV encephalitis, even in the case of postnatally acquired infection, as in an infant we have described.2 Thus, it is possible that neurologic symptoms may be attributable to either CMV encephalitis or HIV-1 encephalitis, or to a combination of both.
In addition, given the achievements in antiretroviral treatment and two recent reports of successful treatment of CMV encephalitis in infants with congenital HIV infection,2,3 should highly active antiretroviral therapy plus anti-CMV treatment (ganciclovir, foscarnet, or both) be recommended for all children who are infected with both HIV-1 and CMV? Might such an approach favorably influence the poor outcomes reported by Kovacs et al.?1
Our experience supports such a recommendation. The infant in our case2 had loss of motor function and increasing spasticity, which led to the diagnosis of CMV encephalitis, confirmed by a positive result for CMV on polymerase-chain-reaction analysis of cerebrospinal fluid.2 After six months of triple-drug antiretroviral treatment in combination with intravenous ganciclovir (four weeks of induction therapy followed by maintenance), the infant had complete neurologic recovery, and culture and polymerase-chain-reaction analysis became fully negative for CMV shedding. After 18 months, ganciclovir treatment was discontinued because of normalization of the CD4 cell count and a marked decrease in the viral load (986 RNA copies per milliliter).
However, CMV shedding reappeared after only two weeks. Intravenous ganciclovir was immediately reintroduced, given the experience in a previously reported case, in which noncompliance was followed by immediate relapse and persisting spasticity.3 After reintroduction of ganciclovir in our patient, CMV shedding disappeared and the infant remained clinically asymptomatic.
Experience in the management of CMV infections in HIV-1–infected children is limited, and recommendations for treatment are lacking. Given the poor outcomes,1 treatment regimens with highly active antiretroviral therapy in combination with anti-CMV drugs should be evaluated in infants infected with both HIV-1 and CMV.
3 ReferencesTilman R. Rohrer, M.D.
Gabriele Engelcke, M.D.
Christoph Rudin, M.D.
University Children's Hospital, 4005 Basel, Switzerland1
Kovacs A ,Schluchter M ,Easley K , et al. Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. N Engl J Med 1999;341:77-84
Full Text | Web of Science | Medline2
Rohrer T ,Rinaldi D ,Bubl R ,Engelcke G ,Di Gallo A ,Rudin C . Combined treatment with zidovudine, lamivudine, nelfinavir and ganciclovir in an infant with human immunodeficiency virus type 1 infection and cytomegalovirus encephalitis: case report and review of the literature. Pediatr Infect Dis J 1999;18:382-386
CrossRef | Web of Science | Medline3
Zaknun D ,Zangerle R ,Kapelari K ,Fischer H ,Sailer M ,McIntosh K . Concurrent ganciclovir and foscarnet treatment for cytomegalovirus encephalitis and retinitis in an infant with acquired immunodeficiency syndrome: case report and review. Pediatr Infect Dis J 1997;16:807-811
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: The case of an infant with CMV encephalitis that Rohrer et al. reported1 lends support to the findings in our study, in which HIV-1–infected infants with early CMV infection were more likely to have central nervous system disease than infants infected only with HIV-1 (35.6 percent vs. 8.7 percent, P=0.005).
Although the successful treatment of this infant with potent antiretroviral therapy and ganciclovir is encouraging, it is premature to suggest that all coinfected children be treated with potent antiviral agents that target both CMV and HIV-1. Although our data strongly support the careful evaluation of HIV-1–infected infants for CMV infection and disease, particularly disease of the central nervous system, our study was conducted before potent combination antiretroviral therapy became available and before early treatment of all HIV-1–infected infants was recommended.2,3 Aggressive treatment of HIV-1 may improve the outlook for coinfected infants and may obviate the necessity of double treatment. In our study we did not examine the blood or central nervous system for CMV DNA to document CMV encephalitis definitively, nor did we test for CMV-specific immunity. Recent information from studies of adults treated with potent antiretroviral agents indicates that immune reconstitution may result in a decrease in CMV viremia and improvement of CMV-specific immunity and CMV disease.4,5 Although these patients may differ from infants with congenital or perinatal CMV infection, additional information from clinical trials or natural-history studies would be useful in making general recommendations.
Thus, we suggest that treatment with antiviral agents that target both viruses be instituted in selected HIV-1–infected patients with clear evidence of CMV viremia or CMV DNA in the cerebrospinal fluid or with characteristics highly suggestive of CMV disease and encephalopathy. In addition, we should consider protocols to examine the value of prophylactic therapy with anti-CMV drugs along with potent antiretroviral therapy in these cases.
5 ReferencesAndrea Kovacs, M.D.
University of Southern California School of Medicine, Los Angeles, CA 90033Gail Demmler, M.D.
Baylor College of Medicine, Houston, TX 77030Kenneth McIntosh, M.D.
Children's Hospital, Boston, MA 021151
Rohrer T ,Rinaldi D ,Bubl R ,Engelcke G ,Di Gallo A ,Rudin C . Combined treatment with zidovudine, lamivudine, nelfinavir and ganciclovir in an infant with human immunodeficiency virus type 1 infection and cytomegalovirus encephalitis: case report and review of the literature. Pediatr Infect Dis J 1999;18:382-386
CrossRef | Web of Science | Medline2
Antiretroviral therapy and medical management of pediatric HIV infectionPediatrics 1998;102:Suppl:1005-1062
Web of Science3
Members of the USPHS/IDSA Prevention of Opportunistic Infections Working Group 4
Macdonald JC ,Torriani FJ ,Morse LS ,Karavellas MP ,Reed JB ,Freeman WR . Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy. J Infect Dis 1998;177:1182-1187
CrossRef | Web of Science | Medline5
Tural C ,Romeu J , Sirera, et al. Long-lasting remission of cytomegalovirus retinitis without maintenance therapy in human immunodeficiency virus-infected patients. J Infect Dis 1998;177:1080-1083
CrossRef | Web of Science | Medline
