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Objectives:\ud To investigate whether there is evidence that an increasing proportion of HIV infected patients is starting to experience increases in viral load and decreases in CD4 cell count that are consistent with exhaustion of available treatment options.\ud \ud Design:\ud Multicentre cohort study.\ud \ud Setting:\ud Six large HIV treatment centres in southeast England.\ud \ud Participants:\ud All individuals seen for care between 1 January 1996 and 31 December 2002.\ud \ud Main outcome measures:\ud Exposure to individual antiretroviral drugs and drug classes, CD4 count, plasma HIV RNA burden.\ud \ud Results:\ud Information is available on 16 593 individuals (13 378 (80.6%) male patients, 10 340 (62.3%) infected via homosexual or bisexual sex, 4426 (26.7%) infected via heterosexual sex, median age 34 years). Overall, 10 207 of the 16 593 patients (61.5%) have been exposed to any antiretroviral therapy. This proportion increased from 41.2% of patients under follow up at the end of 1996 to 71.3% of those under follow up in 2002. The median CD4 count and HIV RNA burden of patients under follow up in each year changed from 270 cells/mm3 and 4.34 log10 copies/ml in 1996 to 408 cells/mm3 and 1.89 log10 copies/ml, respectively, in 2002. By 2002, 3060 (38%) of patients who had ever been treated with antiretroviral therapy had experienced all three main classes. Of these, around one quarter had evidence of “viral load failure” with all these three classes. Patients with three class failure were more likely to have an HIV RNA burden > 2.7 log10 copies/ml and a CD4 count < 200 cells/mm3.\ud \ud Conclusions:\ud The proportion of individuals with HIV infection in the United Kingdom who have been treated has increased gradually over time. A substantial proportion of these patients seem to be in danger of exhausting their options for antiretroviral treatment. New drugs with low toxicity, which are not associated with cross resistance to existing drugs, are urgently needed for such patients.

Editor,—Patients with previous cytomegalovirus retinitis (CMVR) have been observed to get vitritis, cystoid macular oedema (CMO), and epiretinal membranes after commencing HAART (highly active antiretroviral therapy).1-3 It is postulated that this is due to the improved CD4+ function that occurs with HAART.4 We present a patient with previously treated CMVR and immune recovery vitritis who developed further severe intraocular inflammation 6 weeks after changing HAART. ### CASE REPORT A 43 year old man, diagnosed as HIV positive in 1984, was treated in January 1996 for bilateral CMVR that responded to systemic ganciclovir. In April 1996 he started saquinavir, stavudine, and lamivudine. A viral load was 18 000 copies ×106/l and CD4+ count 40 cells ×106/l. In December 1996 ritonavir was added. In February 1997 he developed immune recovery vitritis in both eyes. Best corrected visual acuities (BCVA) were 6/6, N5 right; 6/6, N8 left. A viral …

OBJECTIVE: To estimate median survival and changes in survival in patients diagnosed as having AIDS. DESIGN: Prospective observational study. SETTING: Clinics in two large London hospitals. SUBJECTS: 2625 patients with AIDS seen between 1982 and July 1995. MAIN OUTCOME MEASURES: Survival, estimated using lifetable analyses, and factors associated with survival, identified from Cox proportional hazards models. RESULTS: Median survival (20 months) was longer than previous estimates. The CD4 lymphocyte count at or before initial AIDS defining illness decreased significantly over time from 90 x 10(6)/1 during 1987 or earlier to 40 x 10(6)/1 during 1994 and 1995 (P < 0.0001). In the first three months after diagnosis, patients in whom AIDS was diagnosed after 1987 had a much lower risk of death (relative risk 0.44, 95% confidence interval 0.22 to 0.86; P = 0.017) than patients diagnosed before 1987. When the diagnosis was based on oesophageal candidiasis or Kaposi's sarcoma, patients had a lower risk of death than when the diagnosis was based on Pneumocystis carinii pneumonia (0.21 (0.07 to 0.59). P = 0.0030 and 0.37 (0.16 to 0.83), P = 0.016). Three months after AIDS diagnosis, the risk of death was similar in patients whose diagnosis was made after and before 1987 (1.02 (0.79 to 1.31), P = 0.91). There were no differences in survival between patients diagnosed during 1988-90, 1991-3, or 1994-5. CONCLUSIONS: In later years, patients were much more likely to survive their initial illness, but long term survival has remained poor. The decrease in CD4 lymphocyte count at AIDS diagnosis indicates that patients are being diagnosed as having AIDS at ever more advanced stages of immunodeficiency.