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Clinical sciences poster session 3: HIV
P3-S3.09 New drugs targeting toxicities have highest hope of impacting patient prognosis
  1. M Smit1,
  2. C Smit2,
  3. I Cremin1,
  4. T Hallett1,
  5. F de Wolf2,
  6. G Garnett1
  1. 1Imperial College, London, UK
  2. 2HIV Monitoring Foundation, Amsterdam, Netherlands


Background As more HIV drugs enter the market there is a need to evaluate the effect of various antiretroviral therapies (ART) on patient outcomes. We aim to quantify the impact of different first- and second-line ART strategies on patient outcome including TMC278, an investigative non-nucleoside reverse-transcriptase inhibitors, thought to have low toxicity rates.

Methods A deterministic model was developed representing a cohort of 100 000 HIV-infected individuals. The model was parameterised using data from Athena; a cohort encompassing all patients infected with HIV-1 followed longitudinally since 1996 at 25 HIV treatment centres in the Netherlands. Clinical, biological and immunological data for HIV-infected patients are collected upon entry and at each follow-up visit. The model allows comparison of different ART strategies and of the impact of adverse outcomes: (I) toxicity; (II) general failure and (III) resistance on time on ART and life-years saved per person treated.

Results One of the main reasons for switching treatment is toxicity; therefore, new drugs aimed at reducing toxicity will be valuable. The model shows that if TMC278 can reduce incidence of toxicity leading to discontinuation of first-line ART from 74 to 49 per 1000 patients per year (34%) compared with current treatment then this would equate to one additional life-year saved per patient (Abstract P3-S3.09 figure 1). In comparison, a reduction in general failure from 38 to 25 incidences per 1000 patients per year (34%) adds 6 months and a reduction in resistance from 13 to 1 incidence per 1000 patients per year (92%) adds only 5 months (Abstract P3-S3.09 figure 1). For second-line, reducing incidence of toxicity from 143 to 53 per 1000 patients per year (63%) will add one life-year to per patient. This compares favourably with empirical estimates of toxicity for TMC278 in clinical trials (70% reduction in toxicity leading to discontinuation of first-line ART compared with efavirenz). The model also shows that by reducing rates of toxicity for first-line ART, consequently improving patient prognosis, patients on average spend more time on first-line ART before switching. Decreasing toxicity by 34% equates to an additional 18 months on first-line ART and a 61% decrease in toxicity equates to about five additional years on first-line ART.

Abstract P3-S3.09 Figure 1

Increase in life-expectancy per person treated with reduced annual incidence of adverse outcomes per 1000 patients for first-line ART. The red markers indicate empirical data; the blue markers indicate simulated estimates.

Conclusions New drugs which target a reduction in toxicities have the highest impact on patient prognosis, and such drugs are within reach of current candidate products.

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