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Biomedical subjects

M Youle

Publications and source records attributed to M Youle.

At least 55 records · Page 3Linked to original sources
PubMed1998

Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS.

To assess the effect of intravenous cidofovir on delaying progression of previously treated, relapsing cytomegalovirus (CMV) retinitis, we conducted a randomized, controlled comparison of two maintenance dose levels of cidofovir. One hundred and fifty patients with AIDS and CMV retinitis that had progressed or was persistently active despite treatment with ganciclovir, foscarnet, or both were randomized to receive induction cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with either 5 mg/kg or 3 mg/kg once every other week. Concomitant probenecid and intravenous hydration were administered with each cidofovir dose. Retinitis progression was assessed in the first 100 patients by bilateral, full-field retinal photographs read at a central reading center by an ophthalmologist masked to treatment assignment. Incidence of side effects, changes in visual acuity, and mortality were also assessed. Median time to retinitis progression as assessed by retinal photography was not reached (95% confidence interval [CI], 115 days-upper limit not reached) in the 5-mg/kg group, and was 49 days (95% CI, 35-52 days) in the 3-mg/kg group (p = .0006). Dose-dependent asymptomatic proteinuria (39%) and serum creatinine elevation (24%) were the most common adverse events thought to be related to cidofovir. Reversible probenecid reactions including constitutional symptoms and nausea occurred in 65 of 150 (43%) patients. Cidofovir therapy is effective in delaying progression of CMV retinitis that had previously progressed using other anti-CMV therapies.

AIDS-Related Opportunistic Infections↗
PubMed1998

The incidence of AIDS-defining illnesses in 4883 patients with human immunodeficiency virus infection. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS)-defining illnesses are known to occur at different levels of immunosuppression, and the incidence of diagnoses may also vary according to the CD4 lymphocyte count strata. Information about the incidence of disease at different levels of immunosuppression would help clinicians monitoring patients and would allow prophylaxis to be targeted at the most appropriate population. METHODS: Between 1982 and July 1995, 4883 patients testing positive for the human immunodeficiency virus were seen at either the Royal Free or Chelsea and Westminster Hospitals in London, England. The incidence of each diagnosis, both overall and stratified by CD4 lymphocyte count, was calculated using a person-years analysis. Patients who had no CD4 lymphocyte counts measured during follow-up were excluded from the analysis. RESULTS: During a median follow-up period of 27.6 months, 3875 AIDS-defining illnesses were reported in 1713 patients. The incidence of AIDS-defining illnesses ranged from 6.22 per 100 person-years of follow-up for Pneumocystis carinii pneumonia (95% confidence interval, 5.74-6.70) to 0.37 for extrapulmonary tuberculosis (95% confidence interval, 0.26-0.48). The incidence of each AIDS-defining illness increased as the CD4 lymphocyte count declined; diagnoses such as cytomegalovirus and Mycobacterium avium-intracellulare complex infection had a low incidence at CD4 lymphocyte counts above 0.05x10(9)/L (50/mm3), while Kaposi sarcoma, P carinii pneumonia, and esophageal candidiasis had a high incidence throughout all CD4 lymphocyte count strata. CONCLUSIONS: This study provides important information about the risk of AIDS-defining illnesses at lower CD4 lymphocyte counts, enabling disease-specific prophylaxis to be targeted at the most appropriate population. In the future, as more prophylactic therapies are developed, this study will provide historical data of the incidence of diseases before specific prophylaxis was introduced.

AIDS-Related Opportunistic Infections↗
PubMed1998

Safety, pharmacokinetics, and antiretroviral activity of the potent, specific human immunodeficiency virus protease inhibitor nelfinavir: results of a phase I/II trial and extended follow-up in patients infected with human immunodeficiency virus.

The safety, antiretroviral activity, and pharmacokinetic profile of nelfinavir, a potent and specific inhibitor of human immunodeficiency virus (HIV) protease, were assessed in a small open-label phase I/II dose-ranging study in protease inhibitor-naive HIV-positive men. A total of 22 patients with baseline plasma HIV RNA > or = 20,000 copies/mL and CD4+ counts between 200 and 500 cells/mm3 were enrolled in the study. Of the 22 patients, 20 were evaluated for activity; 10 patients assigned to 771 mg/day base equivalent (300 mg three times daily) and 10 patients assigned to 1,026 mg/day base equivalent (600 mg twice daily) given monotherapy. A capsule formulation of nelfinavir was used. The initial study period was 28 days; patients showing a virologic response of 1 log10 reduction were eligible for enrollment in an extension phase and addition of nucleoside analogues. A maximally tolerated dose of nelfinavir was not established. A dose-response relationship was observed for four (40%) patients in the 771-mg group and six (60%) patients in the 1,026-mg group experiencing a reduction from baseline in plasma HIV RNA of at lest 1 log during the 28-day study. Of these patients, five sustained the reduction in plasma HIV RNA beyond day 28 (2 patients receiving 771 mg/day and 3 patients receiving 1,026 mg/day). Median increases from baseline in CD4+ counts at day 28 were 216 cell/mm3 and 86 cell/mm3 in the 771-mg and 1,026-mg groups, respectively. After oral administration, median nelfinavir plasma concentrations on day 28 reached a maximum at 1 hour (2,966 ng/mL) in the 771-mg group and at 3 hours (3,157 ng/mL) in the 1,026-mg group. Data for 22 patients were included in the safety analysis; 12 patients (55%) reported at least one grade 2 or worse (moderate, severe, or very severe) adverse event. The most common grade 2 or worse adverse event was diarrhea, reported by two patients (20%) receiving 771 mg/day and seven patients (70%) receiving 1,026 mg/day; followed by nausea, flatulence, asthenia, and headache (each reported in 1 patient [10%] in the 771-mg group) and dizziness (reported in 1 patient [10%] receiving 1,026 mg/day). In the small subgroup (n = 6) who continued taking nelfinavir for longer periods (between 8 and 15 months), virologic responses were sustained in the majority of patients with good tolerability. Nelfinavir is an active HIV-protease inhibitor with favorable pharmacokinetics, good tolerability, and sustained antiviral effects. Results of this early phase I/II dose-ranging study provided data for the safety and antiretroviral activity of nelfinavir and led to the selection of higher doses for phase II/III trials to further optimize virologic and immunologic responses.

Adolescent↗
PubMed1998

A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group.

Cytomegalovirus (CMV) disease is a common complication of advanced human immunodeficiency virus (HIV) infection. Administration of oral valaciclovir, a valine ester of acyclovir, achieves sufficient plasma acyclovir levels to inhibit many clinical isolates. Acyclovir has been associated with enhanced survival in AIDS but not with CMV disease prevention. CMV-seropositive patients (1227) with CD4 cell counts <100/mm3 were enrolled in a randomized, double-blind trial. Valaciclovir, 8 g/day, was compared with acyclovir, 3.2 or 0.8 g/day, for CMV prevention; all three arms were compared for survival. The confirmed CMV disease rate was 11.7% among valaciclovir recipients and 17.5% in the pooled acyclovir arms, a 33% reduction in risk. Time to confirmed CMV disease was significantly longer for the valaciclovir group (P = .03). A trend toward earlier mortality for valaciclovir recipients was seen (P = .06). Toxicity and earlier medication discontinuation were more common in this group. Valaciclovir significantly reduces the risk of CMV disease. Further exploration of a better-tolerated dose is warranted.

AIDS-Related Opportunistic Infections↗
PubMed1998

Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection: a randomised, double blind, placebo controlled trial.

BACKGROUND: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but controversy on the efficacy of this treatment persisted. METHODS: We studied 559 adult Ugandan patients with WHO stage 2-4 HIV infection and a Karnofsky performance score of more than 50, who had not received any drugs with antiretroviral activity in the previous 3 months. The patients were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-alpha/day or placebo. The duration of treatment was extended from 28 weeks to 60 weeks 9 months after enrollment had started. At that time 112 subjects had already received 28 weeks of treatment and been discontinued from the study. RESULTS: Both study groups were comparable with respect to all baseline characteristics studied, except that the nHuIFN-alpha group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 x 10(6)/l) than the placebo group (median 85.3 x 10(6)/l) (p = 0.033). Therefore, all analyses were adjusted for CD4+ lymphocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-alpha and placebo had similar mortality, disease progression rates, decline of CD4+ lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms. No patient reverted to HIV-1 seronegative antibody status. Serious adverse events were not seen. Quality control of the study medication documented that the active drug indeed contained IFN-alpha activity. CONCLUSIONS: The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-alpha/day in a population of African patients with symptomatic HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Didanosine once daily: an overview.

The current focus on simplifying treatment regimens for patients with human immunodeficiency virus (HIV) infection has contributed to the interest in once-daily therapy. The triphosphate of didanosine (2',3'-dideoxyinosine or DDI) has a long intracellular half-life, which supports the use of didanosine in a once-daily dosing schedule. Early clinical studies found that changes in surrogate markers were similar whether didanosine was dosed once or twice daily, while toxic effects occurred less frequently with once-daily dosing. Didanosine once-a-day used in combination with other drugs has also been studied, and results of some of these trials are summarized in this paper.

Clinical Trials as Topic↗
PubMed1997

A double-blind placebo-controlled phase II trial of thalidomide in asymptomatic HIV-positive patients: clinical tolerance and effect on activation markers and cytokines.

A randomized double-blind, placebo-controlled study was performed to determine the safety, efficacy, and effect of thalidomide on a variety of immunological and biochemical parameters in asymptomatic human immunodeficiency virus (HIV)-positive patients. Nineteen male patients with elevated markers of immune activation and CD4 cell counts above 400/mm3 were randomized to either placebo or thalidomide at 100 mg/day for 24 weeks. However, only 3 (of 10) patients receiving thalidomide completed all 24 weeks compared to 6 (of 9) patients receiving placebo. This was mainly due to fatigue (somnolence is a recognized side effect), although this was also seen to a lesser extent in the placebo group and so may not be drug attributable. No significant changes in CD4/CD8 count, activation markers, TNF-alpha, or TNFR1 were observed. However, a nonsignificant trend toward inhibition of mitogen-induced TNF-alpha production was observed in the thalidomide arm. The lack of systemic effect and the lower tolerance of thalidomide (at this dose) in asymptomatic patients highlights the need for pharmacokinetic analysis to address possible absorption problems and the need for more potent and less toxic TNF-alpha inhibitors to be developed for use in this type of study.

Adult↗
PubMed1997

Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. A randomized, controlled trial.

BACKGROUND: Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with the acquired immunodeficiency syndrome (AIDS). If left untreated, it may lead to progressive destruction of retinal tissue and blindness. Cidofovir is a nucleotide analogue of cytosine that has potent, prolonged in vitro and in vivo activity against herpesviruses, including many CMV isolates that are resistant to ganciclovir and foscarnet. OBJECTIVE: To determine whether intravenous cidofovir delays progression of previously untreated CMV retinitis. DESIGN: Randomized, controlled trial comparing immediate with deferred cidofovir treatment. Patients in the deferred treatment group were eligible to receive cidofovir after progression of CMV retinitis was documented by retinal photography. SETTING: Eight academic medical centers and an independent center that read retinal photographs. PATIENTS: 48 patients with AIDS and previously untreated peripheral CMV retinitis who were randomly assigned to immediate (n = 25) or deferred treatment (n = 23). INTERVENTION: Intravenous cidofovir, 5 mg/kg of body weight, once weekly for 2 weeks and then once every other week. To minimize nephrotoxicity, oral probenecid and intravenous hydration with normal saline were administered with each cidofovir infusion. MEASUREMENTS: Progression of CMV retinitis was assessed by bilateral, full-field retinal photographs that were read by an ophthalmologist who was masked to treatment assignment. Incidence of side effects, changes in visual acuity, effect on CMV shedding in urine and blood, and mortality were also assessed. RESULTS: The median time to progression of CMV retinitis was 22 days (95% CI, 10 to 27 days) in the deferred treatment group and 120 days (CI, 40 to 134 days) in the immediate treatment group (P < 0.001). Neutropenia (15%) and proteinuria (12%), both asymptomatic, were the most common serious adverse events considered to be possibly related to cidofovir. Cidofovir treatment was discontinued in 10 of 41 patients (24%) because of protocol-defined treatment-limiting nephrotoxicity. Transient reactions to probenecid, including mild to moderate constitutional symptoms or nausea, occurred in 23 of 41 patients (56%) and were dose limiting in 3 (7%). CONCLUSIONS: Cidofovir was efficacious in delaying progression of previously untreated CMV retinitis. Treatment was associated with manageable side effects; strict adherence to monitoring of renal function before cidofovir was administered and concomitant administration of probenecid and saline hydration appeared to minimize drug-related nephrotoxicity.

AIDS-Related Opportunistic Infections↗
PubMed1997

Survival after diagnosis of AIDS: a prospective observational study of 2625 patients. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Ancillary benefits of Mycobacterium avium-intracellulare complex prophylaxis with clarithromycin in HIV-infected patients.

Because of the significant morbidity and mortality associated with opportunistic infections, prophylaxis has become routine practice in the management of immunocompromised patients such as those with AIDS. Clarithromycin, an antimicrobial agent with a broad spectrum of activity against most common respiratory pathogens as well as many protozoa, has proven to be effective for both treatment and prophylaxis of Mycobacterium avium-intracellulare complex (MAC) infection in AIDS patients. Results of a large multinational placebo-controlled study suggest that clarithromycin for MAC prophylaxis provides additional benefits. In this study, clarithromycin statistically significantly reduced the incidence of Pneumocystis carinii pneumonia (5.3% of clarithromycin recipients vs 10.0% of placebo recipients; p = 0.021), community-acquired pneumonia (7.1 vs 13.0%; p = 0.010), Giardia lamblia infection (0.9 vs 2.9%; p = 0.048), and neoplastic diseases (1.8 vs 4.1%; p = 0.010) in AIDS patients with CD4+ counts of < or = 100 cells/microliter.

AIDS-Related Opportunistic Infections↗
PubMed1997

Modelling the cost effectiveness of lamivudine/zidovudine combination therapy in HIV infection.

The use of combination antiretroviral therapy is supported by clinical evidence for its superiority over monotherapy. Lamivudine (3TC) has been studied in combination with zidovudine (ZDV) and is recommended for use specifically in combination therapy. With the associated increase in drug acquisition cost, the economics of combination therapy versus monotherapy warrant study. An economic evaluation was undertaken to compare 3TC/ZDV combination therapy with ZDV monotherapy, taking a UK public finance perspective. The cost effectiveness of each of the 2 treatments was estimated using a Markov model of progression through 3 HIV-positive disease states: (i) CD4 cells > 200 and < 500 cells/mm3; (ii) CD4 < 200 cells/mm3, non-AIDS; and (iii) AIDS to eventual death. Progression probabilities and life expectancy were derived from a cohort treated at Chelsea and Westminster Hospital in London, using data for 1987 to 1995, along with cost data for a ZDV intent-to-treat population for 1994 and 1995. The relative risk of progression for 3TC/ZDV compared with ZDV monotherapy was estimated from meta-analysis of 4 completed comparative trials. To predict the effect of 3TC/ZDV on life expectancy and lifetime costs, progression probabilities were adjusted by the relative risk statistic for the duration of treatment with 3TC/ZDV. On the basis of an estimated relative risk of progression of 0.509 (95% CI 0.365 to 0.710), treatment with 3TC/ZDV is predicted to yield an incremental cost-effectiveness ratio of Pounds 6276 (95% CI Pounds 5337 to Pounds 9075) per life year saved (discounted at 6% per year). Extensive sensitivity analyses were performed to test the effects of varying values of input parameters on the model results. Under reasonable assumptions, the predicted cost effectiveness of 3TC/ZDV combination therapy compares favourably with previously reported economic analyses of various HIV treatments.

Adult↗
PubMed1996

Randomized cross-over comparison of liposomal daunorubicin versus observation for early Kaposi's sarcoma.

OBJECTIVES: To evaluate single-agent liposomal daunorubicin chemotherapy in the management of early HIV-related Kaposi's sarcoma (KS). DESIGN: Randomized cross-over comparison of liposomal daunorubicin versus observation. SETTING: Study conducted at single site in tertiary referral HIV unit. PATIENTS: Twenty-nine HIV-seropositive men with < 20 cutaneous KS, no visceral involvement and CD4 cell counts < 400 x 10(6)/I were randomized. Adequate haematological, hepatic and renal function was required for entry. A left ventricular ejection fraction of > 45% was necessary for eligibility. INTERVENTIONS: Patients were randomized to 12 weeks observation or 12 weeks of liposomal daunorubicin 40 mg/m2 every 2 weeks. After 12 weeks, or at disease progression, patients were crossed over to receive the alternative arm. MAIN OUTCOME MEASURES: Disease evaluation was according to AIDS Clinical Trials Group criteria for response assessment and toxicity was recorded using the World Health Organization standardized grading. RESULTS: Response rate to initial liposomal daunorubicin was six out of 15 (40%) and none experienced a spontaneous response during the observation arm. Six patients (40%) randomized to the initial chemotherapy arm progressed during chemotherapy, while 10(72%) in the observation arm progressed. Neutropenia was the main toxicity associated with liposomal daunorubicin and was documented following 20 out of 139(14%) treatment cycles. CONCLUSIONS: Liposomal daunorubicin is a well tolerated and efficacious treatment for early KS; however, the duration of response is brief.

AIDS-Related Opportunistic Infections↗
PubMed1996

Use of terbinafine in HIV-positive subjects: pilot studies in onychomycosis and oral candidiasis.

Study 1. Eighteen HIV-positive Caucasian homosexual men with initial positive fungal microscopy were recruited into this prospective, dual-centre, open-label study. They received a once-daily oral dose of 250 mg terbinafine for 12 weeks. Eight were subsequently excluded after screening cultures proved negative. The mean CD4 count of the 10 evaluable subjects was 302/mm3. All 10 positive fungal cultures were confirmed as Trichophyton rubrum. Using an intention-to-treat analysis, healthy unaffected nail growth increased from a mean of 1.6 mm at baseline to 5.2 mm after 12 weeks' treatment. Clinical response after treatment was 6.4 mm at 36 weeks and 8.0 mm at 48 weeks. Three of the 10 toenail infections were cured mycologically. This 30% cure rate was maintained over 48 weeks' follow-up, despite three patients discontinuing the study. One withdrew following a terbinafine-induced drug rash. Two others stopped treatment during HIV-related illnesses, but without terbinafine side-effects. Study 2. Ten HIV-positive subjects, nine culture-positive for Candida albicans and one for Candida albicans and Candida glabrata, were recruited into this pilot study. They received 250 mg oral terbinafine daily for 14 days. Their average CD4 count was 131/mm3. All patients remained culture-positive throughout the study. Slight improvements in signs and symptoms were seen in one or two patients but this might well have been attributable to improved oral hygiene. Oral terbinafine at this dosage was therefore not thought an effective treatment for this indication in HIV-positive patients. The drug was well tolerated and no serious treatment-related adverse events were reported.

Antifungal Agents↗
PubMed1996

Anti-herpesvirus treatment and risk of Kaposi's sarcoma in HIV infection. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

OBJECTIVE: With the recent identification of a new herpesvirus in patients with Kaposi's sarcoma (human herpesvirus-8 or Kaposi's sarcoma-associated herpesvirus), there have been several reports on the use of anti-herpesvirus therapy (foscarnet, ganciclovir and aciclovir) and risk of developing Kaposi's sarcoma. We therefore investigated the association between use of anti-herpesvirus drugs and Kaposi's sarcoma in a large unselected group of patients with AIDS. PATIENTS AND METHODS: We studied a group of HIV-positive patients at the Chelsea and Westminster Hospital, for whom details on all AIDS-defining diagnoses made during follow-up, treatment and regular CD4 counts were available. Cox proportional hazards models with time-dependant covariates were used to assess the association between treatment with aciclovir, foscarnet and ganciclovir and risk of Kaposi's sarcoma. RESULTS: A total of 3688 patients have been followed up for a median period of 4.2 years, during which time 598 patients (16.2%) developed Kaposi's sarcoma. After adjustments for sex, exposure category, age, treatment with antiretrovirals or Pneumocystis carinii pneumonia prophylaxis, the development of AIDS-defining conditions (including separate adjustment for the development of cytomegalovirus and herpes simplex virus) and CD4 count, there was a decreased risk of developing Kaposi's sarcoma with foscarnet [relative hazard (RH), 0.38; 95% confidence interval (CI), 0.15-0.95; P = 0.038] and with ganciclovir (RH, 0.39; 95% CI, 0.19-0.84; P = 0.015), but not with aciclovir (RH, 1.10; 95% CI, 0.88-1.38; P = 0.40). CONCLUSIONS: These results suggest that both foscarnet and ganciclovir may have some activity in preventing the occurrence of Kaposi's sarcoma, but that aciclovir has no benefit. Further studies of the effect of these drugs on the risk of Kaposi's sarcoma is warranted.

Acyclovir↗
PubMed1995

Staging system for clinical AIDS patients. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

Although there are wide differences in prognosis between patients with AIDS they are often thought of as a single homogeneous group. We think a simple staging system that accounts for important prognostic factors including type and number of AIDS diseases and the CD4 lymphocyte count is required. We followed 363 AIDS patients at the Royal Free Hospital and reported the occurrence of 680 AIDS-defining diseases (ADDs). We measured CD4 counts at approximately monthly intervals. Severity of AIDS diseases was defined a priori on the basis of survival in the AIDS in Europe study of 6578 AIDS patients: mild-oesophageal candidiasis, Kaposis sarcoma (cutaneous), Pneumocystis carinii pneumonia, extrapulmonary tuberculosis; severe-all other ADDs except lymphoma; very severe-lymphoma. The risk of death increased by 15% (p = 0.08) for each mild condition experienced, by 89% (p < 0.0001) for each new severe condition and by 535% (p < 0.0001) when a lymphoma developed. Estimates from the Cox model were used to derive a score reflecting the risk of death. Patient experience was divided into three categories. Patients in AIDS Grade I had an average death rate of one per 10.1 years, compared with one per 2.8 years in AIDS Grade II and one per 1.1 years in AIDS Grade III. Similar rates were seen in an independent validation study on 1230 AIDS patients at different hospital. Our grading system should be useful for patient management, clinical trial design, surveillance, and resource management.

AIDS-Related Opportunistic Infections↗