Infection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case report

doi:10.1016/S0140-6736(05)71139-9

The Lancet

Volume 365, Issue 9464, 19–25 March 2005, Pages 1031-1038

https://doi.org/10.1016/S0140-6736(05)71139-9 Get rights and content

Summary

Background

Rapid progression to AIDS after acute HIV-1 infection, though uncommon, has been noted, as has the transmission of multidrug resistant viruses. Here, we describe a patient in whom these two factors arose concomitantly and assess the effects.

Methods

We did a case study of a patient with HIV-1 seroconversion. We genotyped the virus and host genetic markers by PCR and nucleotide sequencing. To ascertain the drug susceptibility of our patient's HIV-1 we did phenotypic studies with the PhenoSense assay. We assessed viral coreceptor use via syncytium formation in vitro and with a modified PhenoSense assay.

Findings

Our patient seems to have been recently infected by a viral variant of HIV-1 resistant to multiple classes of antiretroviral drugs. Furthermore, his virus population is dual tropic for cells that express CCR5 or CXCR4 coreceptor. The infection has resulted in progression to symptomatic AIDS in 4–20 months.

Interpretation

The intersection of multidrug resistance and rapid development of AIDS in this patient is of concern, especially in view of his case history, which includes high-risk sexual contacts and use of metamfetamine. The public health ramifications of such a case are great.

Introduction

Combination antiretroviral therapy has reduced the rates of death and progression to AIDS in people with HIV-1.1, 2 Today, HIV-1 infection can be managed with simple regimens in most infected individuals in developed countries. Along with this therapeutic success, however, has come the emergence of drug resistant HIV-1 in chronically treated patients³ and in some recently infected people.4, 5, 6, 7, 8

HIV-1 is classified as either non-syncytium inducing or syncytium inducing,⁹ and the identification of the chemokine receptors CCR5 and CXCR4 as a necessary entry cofactor has provided a mechanistic explanation for the differences between these virus types;10, 11 CCR5-tropic viruses are non-syncytium inducing in phenotype and they dominate in early infection,¹² whereas HIV-1 strains that use CXCR4 as a coreceptor are generally syncytium inducing in phenotype and emerge in about half of patients who progress to AIDS.9, 13, 14 CXCR4-tropic or dual-tropic variants are uncommon in newly infected individuals, but their existence is well documented.¹⁵ In fact, transmission of CXCR4-tropic viruses has been reported in individuals who are homozygous for a non-functional CCR5 gene.16, 17, 18

The natural history of HIV-1 infection varies widely between hosts, and can be affected by both viral¹⁹ and host²⁰ factors. On average, development of AIDS and eventual death arise after years of infection.²¹ However, cases of rapid progression to immunodeficiency have been reported.15, 16, 17, 18, 21, 22 In some of these patients, CXCR4-tropic or dual-tropic viruses were identified at the outset of infection, suggesting that such viral strains might result in a faster clinical course. It is noteworthy, however, that genetic markers were not adequately analysed in all these cases and cannot therefore be excluded as contributory factors.

Here, we report and analyse a case of infection with a multidrug resistant, dual-tropic HIV-1 virus that resulted in progression to symptomatic AIDS in 4–20 months.

Section snippets

Methods

Between December, 2004, and February, 2005, we assessed one patient (panel 1)²³ with documented HIV-1 seroconversion. The patient provided signed informed consent to do all studies described.

To assess the susceptibility of our patient's HIV-1 to antiretroviral drugs, we sequenced the viral pol gene and the gp41 envelope open reading frame (Trugene, Bayer Diagnostics, Tarrytown, NY, USA) in a plasma sample from mid-January, 2005. We also did phenotyping studies with the PhenoSense assay

Results

The results of genotyping studies to ascertain the drug susceptibility of our patient's HIV-1 are summarised in panel 2 and reveal broad resistance to nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitors. The genotype was confirmed by further testing done at ViroLogic with one notable difference: the detection of a mixture of M184V/I in reverse transcriptase (RT). We interpret the collection of mutations to confer

Discussion

Rapid progression to AIDS after acute HIV-1 infection has been described previously,15, 16, 17, 18, 21, 22 as has the transmission of multidrug resistant viruses.4, 5, 6, 7, 8, 38, 39, 40, 41, 42 The unique feature in this case is the convergence of two uncommon factors: the transmission of a multidrug resistant HIV-1 variant and the extremely rapid clinical course to AIDS. The duration of infection in this case cannot have been longer than 20 months, since the patient had five negative HIV-1

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Actualizar las recomendaciones sobre el tratamiento antirretroviral (TAR) para adultos infectados por el virus de la inmunodeficiencia humana tipo 1 (VIH-1).
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Fast track — ArticlesInfection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case report

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

Lancet

Cell

Lancet

Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection

N Engl J Med

The prevalence of antiretroviral drug resistance in the United States

AIDS

Sexual transmission of an HIV-1 variant resistant to multiple reverse-transcriptase and protease inhibitors

N Engl J Med

Antiretroviral-drug resistance among patients recently infected with HIV

N Engl J Med

HIV-1 drug resistance in newly infected individuals

JAMA

Evolving patterns of HIV-1 resistance to antiretroviral agents in newly infected individuals

AIDS

Time trends in primary HIV-1 drug resistance among recently infected persons

JAMA

Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS

Ann Intern Med

HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5

Nature

HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor

Science

Genotypic and phenotypic characterization of HIV-1 patients with primary infection

Science

The impact of the syncytium-inducing phenotype of human immunodeficiency virus on disease progression

J Infect Dis

Conversion rate towards a syncytium-inducing (SI) phenotype during different stages of human immunodeficiency virus type 1 infection and prognostic value of SI phenotype for survival after AIDS diagnosis

J Infect Dis

Infection with dual-tropic human immunodeficiency virus type 1 variants associated with rapid total T cell decline and disease progression in injection drug users

J Infect Dis

HIV-1 infection in individuals with the CCR5-Delta32/Delta32 genotype: acquisition of syncytium-inducing virus at seroconversion

J Acquir Immune Defic Syndr

Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient

AIDS

Exclusive and persistent use of the entry coreceptor CXCR4 by human immunodeficiency virus type 1 from a subject homozygous for CCR5 delta32

J Virol

Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1: a report from the Sydney Blood Bank Cohort

N Engl J Med

Host determinants in HIV infection and disease, part 2: genetic factors and implications for antiretroviral therapeutics

Ann Intern Med

Acquired immunodeficiency syndrome (AIDS)-free time after human immunodeficiency virus type 1 (HIV-1) seroconversion in homosexual men

Am J Epidemiol

Fast track — Articles
Infection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case report