Case of multi-drug resistant (MDR) rapid progressor
18 April 2005. Related: Conference reports, Basic science and immunology, CROI 12 (Retrovirus) 2005.
Simon Collins, HIV I-Base
One individual case study, partly presented before the conference, generated a lot of activity at the meeting for several reasons.
Part of the controversy related to this case having been presented in a New York City Department of Health press conference two weeks prior to this strictly embargoed meeting, dominating media attention. It was then admitted as a late poster [1] and allotted an additional four-speaker oral symposium that was added to the programme for Thursday evening and which has been added to the webcast presentations. [2]
This was a man from New York in his late 40’s who had been infected within the last 4-20 months (previous antibody test was negative in May 2003, clinical history suggested infection within last 6 months). He was symptomatic with weight loss, fatigue and had a sustained CD4 count of 80 cells/mm3.
This patient had a approximate 60%/40% mixture of R5 and R5/X4 dual tropic virus, associated with later stage disease. Additionally, he had Multi-Drug Resistance at baseline* including resistance to RTIs, PIs and nevirapine. The replicative capacity of this MDR resistant virus had similar in vitro fitness to wild-type HIV.
The context of the original press conference also focused on the co-factors of recreational use of crystal methamphetamine and history of multiple sex partners over the previous year. Many advocates saw as this as generating unhelpful media attention that targeted gay men in an alarmist way, with little supporting data, and without mentioning the context of reduced funding for public health programmes.
Cases of transmission of MDR virus have been reported for many years, without evidence of a widespread ‘superbug’ that the press reports then focused on. Although generally transmitted virus doesn’t have reduced fitness when this is a patients reference strain, this was not made clear in the original presentations.
It seems more likely that this individual is one of the unlucky rapid progressors. MACS and WIHS cohort data show approximately 1% people progress to CD4 < 200 cells/mm3 within 1 year and modeled that 0.1% progress within 6 months. In the US Military Cohort 15/2700 seroconvertors progressed to AIDS at one year.
Prevention issues are certainly important, though this was barely addressed in the presentations. There are around 40,000 new diagnoses in the US annually, and a separate poster estimated that there are over 120-150,000 HIV-positive individuals live in New York. [3]
This scale of treatment access in the US was also highlighted in an oral presentation from showing that less than 50% of people in the US who could clinically benefit form treatment actually receive it. [4]
This case study was published just after the conference, together with and editorial in the 19 March issue of The Lancet. [5]
* Mutations shown by genotyping: NRTI: M41L/A, D67D/N, V118I, M184V/I, L210L/G/M/R/V/W, T215C/Y, K219E; NNRTI: K101E, Y181I; Protease: L10I, L33F, E34Q, M46I, I54M, L63P, A71V, G73S, V77I, I84V, L89V, L90M.
References:
- 1. Markowitz M, Mohri H, Ho D et al – A case of recent infection with a multi-drug-resistant and dual-tropic HIV-1 in association with rapid progression to AIDS. 12th CROI, Boston, 2005, Poster 973b. (Abstract not online).
- 2. Special Symposium: Transmitted HIV-1 Drug Resistance and Rapid Disease Progression. Webcast Thursday 24 February. 12th CROI, Boston, 2005,
- 3. Torian LV, Bennani Y, Frieden T – What is the True Prevalence of HIV in New York City?: Estimating the Number of Undiagnosed and Unreported Persons Living with HIV and AIDS in 2002. 12th CROI, Boston, 2005,
Poster 970. - 4. Teshale E, Kamimoto L, Harris N et al. Estimated Number of HIV-infected Persons Eligible for and Receiving HIV Antiretroviral Therapy, 2003—United States. 12th CROI, Boston 2005.
Abstract 167. - 5. Fast-track article and editorial in The Lancet, 19 March 2005; 365: 1031-38