Correspondence

Case 11-2009: A Man with Fever, Headache, Rash, and Vomiting

N Engl J Med 2009; 361:312-314July 16, 2009

Article

To the Editor:

In the Case Record of a man with fever and rash (April 9 issue),1 acute infection with the human immunodeficiency virus (HIV) was the definitive diagnosis. The rash in acute HIV infection is commonly described as maculopapular or morbilliform.2 The authors note that the rash in this patient was nonvesicular, which is why they excluded infection with varicella–zoster virus (VZV). On the other hand, acute HIV infection cannot be ruled out in the presence of a vesicular rash. We evaluated a 28-year-old man presenting with fever and a diffuse vesicular eruption associated with some pustular and crusted lesions (Figure 1Figure 1Diffuse Vesicular Rash.). The clinical diagnosis of varicella was made, but serologic analysis did not confirm primary VZV infection, and the rash resolved without antiviral therapy. Acute HIV infection was suspected and diagnosed on the basis of quantitative HIV RNA analysis (5 million copies per milliliter) with negative anti-HIV serologic tests.

Acute HIV infection can have protean clinical presentations, and a high rate of misdiagnosis is reported.3 This syndrome should be included in the differential diagnosis of a varicella-like rash.

Cosmo Del Borgo, M.D., Ph.D.
Fabrizio Soscia, M.D.
S.M. Goretti Hospital, 04100 Latina, Italy
cosmodel@tiscalinet.it

Claudio M. Mastroianni, M.D., Ph.D.
La Sapienza University, 04100 Latina, Italy

3 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 11-2009). N Engl J Med 2009;360:1540-1548
   Full Text | Web of Science | Medline

2. 2

   Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med 1998;339:33-39
   Full Text | Web of Science | Medline

3. 3

   Weintrob AC, Giner J, Menezes P, et al. Infrequent diagnosis of primary human immunodeficiency virus infection: missed opportunities in acute care settings. Arch Intern Med 2003;163:2097-2100
   CrossRef | Web of Science | Medline

To the Editor:

In the Case Record of a patient with acute HIV infection, the decision to initiate antiretroviral therapy was inappropriate. His physician should have ordered and awaited the results of an assay for drug resistance before selecting components of a medication regimen. Although this monogamous patient was most likely infected by a partner who had not received previous treatment, that partner (who had reportedly been HIV-positive for 4 years) might have been infected with a drug-resistant strain. Mutations conferring drug resistance have been found to persist for many years, despite the absence of selective pressure.1 Two of the three medications in this patient's regimen, efavirenz and emtricitabine, have low genetic barriers to resistance. If even one mutation were present, the viral population would rapidly acquire resistance to the entire treatment combination. Given that chronic HIV infection is so manageable, clinicians should avoid a rush to treat acute primary infection. Treatment guidelines strongly recommend obtaining baseline drug-resistance testing.2

Steven Leiner, N.P.
Mission Neighborhood Health Center, San Francisco, CA 94110
stevenleiner@hotmail.com

2 References

1. 1

   Shulman NS, Zolopa AR. Resistance. In: AAHIVM fundamentals of HIV medicine. Washington, DC: American Academy of HIV Medicine, 2007:781-808.
   

2. 2

   Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Washington, DC: Department of Health and Human Services, November 3, 2008. (Accessed June 25, 2009, at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.)
   

Author/Editor Response

Acute HIV infection can manifest with many presenting symptoms. The most common rash is a maculopapular eruption,1 as described in our case. However, other presentations are possible, particularly if the patient has a coexisting secondary infection, such as syphilis or VZV infection. Reactivation of a latent, chronic viral infection would not be surprising, given the transient immunosuppression associated with a decline in the number of CD4+ T cells that is typical of acute HIV infection. In the interesting case described by Del Borgo et al., it remains uncertain whether the patient had acute HIV alone or a concurrent VZV eruption, which the skin findings suggest. The greatest diagnostic yield would have been derived from viral culture or direct fluorescent antibody from an active skin lesion, regardless of the results of VZV serologic analysis. The lesions might have healed without specific antiviral therapy in either case.

Leiner questions whether we should have waited until the results of drug-resistance testing were available before initiating antiretroviral therapy. We ordered drug-resistance testing for our patient, as recommended by the treatment guidelines.2 However, we decided to initiate therapy while awaiting the results for the following reasons. First, we knew that his likely source partner had drug-sensitive virus, which informed our decision to choose an efavirenz-based regimen. Had we not known the drug sensitivity of the source partner, we would have considered a protease inhibitor–based regimen (which has a higher genetic barrier to resistance) while awaiting genotypic results, as recommended by treatment guidelines. Second, we typically receive genotypic results within 2 to 3 weeks. Therapy in this patient was started with the expectation that we would have this information back shortly, allowing us to adjust the regimen rapidly if needed. Third, the patient had severe and ongoing signs and symptoms of meningitis, which we felt that early therapy would ameliorate. Some guidelines suggest routine consideration of acute HIV treatment in patients with neurologic involvement.3 Finally, a delay in the initiation of therapy might have resulted in the impairment of important CD4+ T cells, which are rapidly depleted within a few weeks after infection.4,5

Sigall K. Bell, M.D.
Beth Israel Deaconess Medical Center, Boston, MA 02115
sbell1@bidmc.harvard.edu

Rajesh T. Gandhi, M.D.
Massachusetts General Hospital, Boston, MA 02114

5 References

1. 1

   Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med 1998;339:33-39
   Full Text | Web of Science | Medline

2. 2

   Hammer SM, Eron JJ Jr, Reiss P, et al. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 2008;300:555-570
   CrossRef | Web of Science | Medline

3. 3

   Gazzard BG. British HIV Association guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008. HIV Med 2008;9:563-608
   CrossRef | Web of Science | Medline

4. 4

   Brenchley JM, Schacker TW, Ruff LE, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004;200:749-759
   CrossRef | Web of Science | Medline

5. 5

   Rosenberg ES, Billingsley JM, Caliendo AM, et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 1997;278:1447-1450
   CrossRef | Web of Science | Medline