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Date: Fri 24 Feb 2005

From: ProMED-mail <promed@promedmail.org>

Source: Eurosurveillance Weekly 2005; 10(8): 24 Feb [edited]

<http://www.eurosurveillance.org/ew/2005/050224.asp>

New York: multidrug-resistant HIV and rapid progression of disease reported

A single case of infection with a highly drug-resistant strain of human immunodeficiency virus (HIV) that progressed rapidly has been diagnosed in a New York City resident who had not previously undergone antiviral drug treatment (1). The individual was infected within the previous 20 months, suggesting that the resistant virus had been transmitted relatively recently. The virus strain has reduced susceptibility to drugs in 3 of the 4 available classes currently available. In addition, there appears to have been a very short time interval between HIV infection and the onset of AIDS. No other cases of this particular strain of transmitted virus have been documented in New York. There is, however, very limited surveillance of this type currently undertaken in New York City.

This case is noteworthy for 2 reasons (2). Firstly, transmission of HIV-1 resistant to drugs within 3 of the 4 available classes of anti-retroviral drugs occurred recently, and secondly, disease progression was rapid. Although each of these occurrences is rare, they are both previously documented in the literature, and may be independent of each other.

The prevalence of transmitted HIV-1 drug resistance in the United Kingdom (UK) and the rest of Europe is assessed by surveillance of resistance in drug-naive individuals, and also in those individuals with recent infection, which is more comparable to the case described above. The UK HIV Resistance Database recorded a prevalence of any form of transmitted resistance of 18 per cent within 2410 drug-naive individuals studied between 1996 and 2003, with 3 per cent infected with 3-class resistant virus in 2002 (3). A similar data set from the Europe-wide CATCH study reported 10 per cent (of a population of 1633) with any form of resistance between 1998 and 2002 (4).

The largest data set from individuals with recent infection (thus allowing more accurate estimation of time trends for transmitted resistance) comes from the Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE), a large collaboration of seroconverter cohort data. Of 453 such individuals known to have been infected from 1987 to 2003, 12 per cent had any form of resistance at diagnosis, with a peak of 19 per cent in 1999. Only 0.5 per cent were infected with 3-class resistant HIV (5). Since such cohorts allow follow-up of recruited individuals with a known time of infection, it is possible to explore the impact of transmitted resistance in the absence of therapy on CD4 decline, as a surrogate for disease progression. Such analysis of the UK Register of HIV Seroconverters over a 5 year follow-up period showed no difference in disease progression between those infected with resistant virus and those without (6). This suggests that the rapid progression in the recent New York case was not necessarily due to the resistance pattern of the infecting virus strain.

Taken together, these data sets show that transmission of drug resistance is evident in the United Kingdom (UK) and Europe as a whole. Although infection with such strains will compromise response to first line anti-retroviral therapy, there is little evidence to date, that such transmission is itself associated with increased pathogenicity or faster disease progression. Nevertheless, there exists a myriad of forms of HIV resistance. The possibility that particular resistant variants, currently at low frequency in the population, are more transmissible than others, or are more damaging cannot be excluded. In view of the ongoing transmission of HIV within Europe, such a possibility must be considered (7).

It is important to maintain large-scale population-based surveillance of transmitted resistant viruses. In particular, linking such data to clinical cohort follow-up will be essential for the early detection of viruses that respond poorly to anti-retroviral therapy and/or cause rapid disease progression.

(This article was adapted from reference 2 below.)

References

1. New York City Department of Health and Mental Hygiene. New York City resident diagnosed with rare strain of multi-drug resistant HIV that rapidly progresses to AIDS (press release). New York, United States: New York City Department of Health and Mental Hygiene, 11 Feb 2005 [cited 21 Feb 2005] (<http://www.nyc.gov/html/doh/html/public/press05/pr016-05.html>)

2. Health Protection Agency. Multidrug resistant HIV and rapid progression of disease: a single case in New York. Commun Dis Rep Wkly (Online) 2005; 15(8): news. (<http://www.hpa.org.uk/cdr/index.html>)

3. Health Protection Agency. An update on HIV drug resistance in the United Kingdom. Commun Dis Rep Wkly [serial online] 25 Nov 2004 [cited 21 Feb 2005]; 14 (48): HIV/STIs. (<http://www.hpa.org.uk/cdr/PDFfiles/2004/cdr4804.pdf>).

4. Wensing AMJ, et al. The CATCH Study: Combined analysis of resistance transmission over time of chronically and acutely infected patients in Europe. The 2nd IAS Conference on HIV Pathogenesis and Treatment, 13-17 Jul 2003; Paris, France. Abstract LB01. (<http://www.iasociety.org/abstract/show.asp?abstract_id=11112>)

5. B Masquelier, et al. Changes in Prevalence and Characteristics of Transmitted Resistance over Time among European Seroconverter Cohort. Program and abstracts of the 11th Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8-11; San Francisco, California, USA. Abstract 683.

6. Bhaskaran K, Pillay D, Walker AS, Fisher M, Hawkins D, Gilson R, et al. Do patients who are infected with drug-resistant HIV have a different CD4 cell decline after seroconversion? An exploratory analysis in the UK Register of HIV Seroconverters. AIDS 2004; 18: 1471-3.

7. Murphy G, Charlett A, Jordan LF, Osner N, Gill ON, Parry JV. HIV incidence appears constant in men who have sex with men despite widespread use of effective anti-retroviral therapy. AIDS 2004; 18: 265-72.

[Reported by: Deenan Pillay 1,2 (<d.pillay@ucl.ac.uk>) and John Parry 2 1=Centre for Virology, University College London, United Kingdom 2=Sexually Transmitted & Bloodborne Virus Laboratory (SBVL), Health Protection Agency Centre for Infections, London, United Kingdom]

ProMED-mail <promed@promedmail.org)

[The discussion in this report casts further doubt on the uniqueness of the New York City case of an HIV-1 patient exhibiting triple anti-retroviral drug resistance, and the untested assumption that triple-drug resistance and rapid progression to AIDS in the New York patient are necessarily associated. - Mod.CP]

[see also:

HIV, multi-drug resistant - USA (New York City) (03) 20050222.0568

HIV, multi-drug resistant - USA (New York City)(02) 20050216.0522

HIV, multi-drug resistant - USA (New York City) 20050212.0476

2004

HIV/AIDS, global epidemic escalates 20040706.1814

2003

HIV-1: origin & history 20030614.1463

HIV-2: origin and history 20030514.1201

2002

HIV/AIDS, origin and evolution 20020119.3310

HIV recombinants, global spread 20020520.4283

2001

HIV, multi-drug resistant - Canada (British Columbia) 20010810.1892]
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