Disease Progression in Patients with residual HIV infection on First-line Anti-retroviral Therapy in the UK 1996-2000: treatment and cost implications.

Mandalia S¹, Baily G², Brettle R², Fisher M², Gompels M², Kinghorn G², McCarron B², Ong E², Pozniak A², Tang A², Youle M¹ Gazzard B¹ and Beck EJ¹ on behalf of the NPMS-HHC Steering Group. ¹NPMS-HHC Coordinating Analytic Centre, Chelsea & Westminster Hospital, London; ²NPMS-HHC Sites (UK).

Background: The aim of the National Prospective Monitoring System- HIV Health-economics Collaboration ( NPMS-HHC) is to monitor prospectively on a multi-centre basis, the use, cost and outcome of HIV service provision in the UK. The scheme has been in operation since 1996 and now covers 21 sites. Material and Methods: The study period was between the 1^st January 1996-31^st December 2000. Data were collected from 10 NPMS-HHC sites. The aim is to describe treatment and cost implications of residual HIV infection in patients managed with a combination of 2NA+1NNRTI compared with 2NA+1PI (including PI boosted) as first line triple anti-retroviral therapy. Results: 106 people with CDC Group A started on either 2NA+1NNRTI or 2NA+1PI. Of these, 16 (15.1%) progressed either to CDC Group B, C and one died. 148 with CDC Group B commenced triple HAART, of whom 12 (10.8%) progressed to AIDS and 4 died. Of those 223 AIDS patients who started first line triple therapy, 17 (7.6%) died by the end of the study period. There were no significant differences in rates of progression for people who were started with a NNRTI or PI containing HAART regimen, for asymptomatic patients (CDC Group A; Log-Rank c²=4.57, p=0.207), people with symptomatic non-AIDS (CDC Group B; Log-Rank c²=1.25, p=0.536) and people with AIDS (CDC Group C; Log-Rank c²=1.43, p=0.490). CD4 count at start of HAART for the different stages of HIV infection did not show significant differences in the rate of HIV disease progression.  Average annual cost of treating patients with 2NA+1NNRTI amounted to £8000 compared with an average of £10,000 for treating HIV infected patients with 2NA+PI.  Additional direct hospital costs amounted to £2,800 per annum for asymptomatic patients (CDC Group A),  £5,000 for patients with symptomatic non-AIDS (CDC Group B) and £13,700 per annum for AIDS patients (CDC Group C). Conclusion: This cost-minimization study reinforces the limited effectiveness of contemporary HAART regimens given that HIV infected people continue to progress while undergoing treatment with both regimens. While, other causes of death could have included drug toxicities, malignancies, pre-existing HIV related co-morbidity in patients who had HIV diagnosed late or other non HIV-related causes of death, the major reason for disease progression is likely to be due to the limited effectiveness of contemporary anti-retroviral drugs  which result in the persistence of HIV and residual viral replication. This is most likely to occur in those body compartments where contemporary antiretroviral drugs can poorly penetrate. The cost of ART also influences the type of drugs that are used in health care provision of industrialised countries, indicating a strong need for drugs which are more effective in eliminating residual virus and viral replication and which are also cost-effective. This is even more pertinent for resource poor settings in which the scale-up of anti-retroviral therapy is currently being implemented.