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Clinical features of acute HIV-1 infection: zidovudine-resistant isolates compared with zidovudine-sensitive isolates

Vanhems, Philippea; Gaudet, Rollandb; Hirschel, Bernardc; Imrie, Allisond*; Conway, Briane; Rouleau, Daniellef; Vizzard, Jeanetted; Perrin, Lucc; Cooper, David A.d; Yerly, Sabinec

Correspondence

aLaboratoire d'Epidémiologie et de Santé Publique-INSERM U-271, Université Claude Bernard, Lyon, France; bDepartment of Social and Preventive Medicine, Université de Montréal, Montréal, Canada; cLaboratory of Virology, University Hospital, Geneva, Switzerland; dNational Center in HIV Epidemiology and Clinical Research, Sydney, Australia; eDepartment of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada; and fUniversité de Montréal, Montréal, Canada.

Sponsorship: This study has been financed in part by GlaxoWellcome Canada. The Swiss HIV Cohort Study has been financed by the Swiss Federal Office of Public Health. The National Centre in HIV Epidemiology and Clinical Research is supported by the Australian National Council on AIDS through the Comonwealth AIDS Research Grants Committee. This study was presented in part at the 12th World AIDS Conference, Geneva, 28 June–3 July 1998, Poster no. 12184.

*Allison Imrie, PhD, is currently at the University of Hawaii, at Manoa.

Received: 7 January 2000; accepted: 19 January 2000.

The transmission of isolates resistant to zidovudine (ZDV) was initially reported in 1992 [1]. The prevalence of primary ZDV resistance is as high as 10% in some countries [2]. Case reports suggested that acute HIV infection with ZDV resistance is exceptionally severe [1,3]. We compared the clinical features of patients recently infected with ZDV-resistant strains to those infected with ZDV-sensitive strains.

These subjects were taken from patients participating in a clinical trial [4], or from cohorts established by the Division of Infectious Diseases at the University Hospital of Geneva, Switzerland [5], the National Center for HIV Epidemiology and Clinical Research of Sydney, Australia [6] and the University of British Columbia, Vancouver, Canada [7]. Among this cohort extensively described [8], the presence of ZDV resistance was determined by means of a selective polymerase chain reaction assay designed to detect the T215Y or F mutation [9]. Each patient with the 215 mutation (resistant group, n = 13) was matched with three, or four when available, patients with susceptible isolates (non-resistant group, n = 44). The matching was based on the same time delay (within 2 days) from the onset of acute HIV infection to the virus analysis. Patients were recruited between 1988–1991 (n = 13), 1992–1993 (n = 30) and 1994–1995 (n = 14).

The diagnosis of acute/early HIV infection was based on the following criteria: negative or weakly positive HIV antibody enzyme immunoassay test with positive p24 antigenemia (n = 47); negative or weakly positive HIV antibody enzyme immunoassay test with indeterminate Western blot confirmatory test (n = 7); documented HIV seroconversion within the previous year (n = 3). In subsequent follow-up, all patients were shown to be positive for HIV antibodies by Western blot. The comparisons of proportions were carried out using the Chi squared or Fisher's exact test, as appropriate. The Mann–Whitney U-test was used for comparisons of distributions of continuous variables.

The median time between the onset of acute HIV-1 infection and the evaluation of ZDV resistance was 25 days. The proportion of men was 84 and 90% in the resistant and sensitive groups, respectively (P  = 0.61). The routes of infection were homosexual or bisexual intercourse for 10 (77%) individuals in the resistant group and for 25 individuals (57%) in the sensitive group (P  = 0.32). As shown in Table 1, there was no difference in clinical characteristics between the two groups, except for the slightly longer duration of oral ulcers (P  = 0.04) and a trend towards more prevalent cervical adenopathy (P  = 0.09) in the sensitive group. In view of the number of comparisons made, these differences may be due to chance. A total of eight out of 13 (61%) patients with resistant isolates received ZDV, compared with 15 out of 44 (34%) drug-sensitive individuals (P  = 0.11).

Table 1

Table 1

Infection with mutant strains thus does not appear to lead to more severe symptoms at the time of infection, as reported by others in the absence of a control group [1,3]. On the other hand, a hypothetical decrease of viral fitness related to the genotype mutation did not seem to facilitate the emergence of more severe symptoms in the sensitive group [10].

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Acknowledgements

The authors are indebted to F. Lemay, C. Perron, R. Read (Montreal), and M.A. Trabaud (Lyon).

Philippe Vanhemsa

Rolland Gaudetb

Bernard Hirschelc

Allison Imried*

Brian Conwaye

Danielle Rouleauf

Jeanette Vizzardd

Luc Perrinc

David A. Cooperd

Sabine Yerlyc

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