The effect of an abuse-deterrent opioid formulation (OxyContin) on opioid abuse-related outcomes in the postmarketing setting.

An extended-release opioid analgesic (OxyContin, OC) was reformulated with abuse-deterrent properties to deter abuse. This report examines changes in abuse through oral and nonoral routes, doctor-shopping, and fatalities in 10 studies 3.5 years after reformulation. Changes in OC abuse from 1 year before to 3 years after OC reformulation were calculated, adjusted for prescription changes. Abuse of OC decreased 48% in national poison center surveillance systems, decreased 32% in a national drug treatment system, and decreased 27% among individuals prescribed OC in claims databases. Doctor-shopping for OC decreased 50%. Overdose fatalities reported to the manufacturer decreased 65%. Abuse of other opioids without abuse-deterrent properties decreased 2 years later than OC and with less magnitude, suggesting OC decreases were not due to broader opioid interventions. Consistent with the formulation, decreases were larger for nonoral than oral abuse. Abuse-deterrent opioids may mitigate abuse and overdose risks among chronic pain patients.

Indinavir did not increase the short-term risk of adverse cardiovascular events relative to nucleoside reverse transcriptase inhibitor therapy in four phase III clinical trials.

A retrospective person-time analysis of the randomized and non-randomized extension phases of four phase III trials was performed to assess the incidence of adverse cardiovascular events in 2680 HIV-infected patients receiving indinavir or nucleoside reverse transcriptase inhibitor therapy, or both. The observed rate of cardiovascular events was not increased in patients receiving indinavir-based regimens compared with therapy without a protease inhibitor. Extrapolation of these findings is limited by the brief length of therapy and the small number of cases.

Modeling the long-term outcomes and costs of HIV antiretroviral therapy using HIV RNA levels: application to a clinical trial.

A model was developed to gain insight into the potential clinical and economic impact of antiretroviral therapy for HIV-infected patients. Observed HIV RNA levels and CD4 cell counts are used in the model to estimate the probability that an individual progresses from asymptomatic infection to the first AIDS-defining illness and death and to estimate the total net cost of care and long-term cost-effectiveness of antiretroviral therapy. The model was applied to patients in a clinical trial (Merck protocol 035) that compared the surrogate marker response to triple therapy with indinavir (IDV; 800 mg every 8 hr) plus zidovudine (ZDV; 200 mg every 8 hr) plus lamivudine (3TC; 150 mg twice a day) to double therapy with ZDV+3TC. The model projected that for an individual without AIDS who received triple therapy the progression to AIDS and death would be delayed more than for a patient who received double therapy with ZDV+3TC if no other treatment options were offered. Because of this delay in disease progression, the total discounted cost over the initial 5-year period was projected to be $5100 lower for patients who received triple therapy compared with double therapy if suppression with triple therapy lasts up to 3 years. If suppression with triple therapy lasts up to 5 years, costs were projected to be higher with the triple combination, but 81% of the cost is offset by lower disease costs as a result of fewer patients progressing to AIDS. Over 20 years, total discounted cost was projected to be higher for the triple-therapy regimen primarily because of a longer estimated survival time. At 20 years, the incremental cost per life-year gained by adding IDV to a ZDV+3TC regimen was estimated at $13,229, which is well within the range of other widely accepted medical interventions.

Incidence and hospitalization rates of varicella and herpes zoster before varicella vaccine introduction: a baseline assessment of the shifting epidemiology of varicella disease.

BACKGROUND: A 15-year postmarketing evaluation of the impact of varicella vaccine on the age distribution of varicella disease is being conducted at Kaiser Permanente Medical Care Program, Northern California (KPMCP). We report on a baseline assessment of the age-specific incidence and hospitalization rates of varicella and herpes zoster that was conducted before vaccine introduction. METHODS: To assess the annual incidence of varicella, a telephone survey was conducted in a random sample of approximately 8,000 youths 5 to 19 years of age. The annual incidence of hospitalizations for varicella and herpes zoster in 1994 was assessed with the use of the computerized database at KPMCP. RESULTS: Varicella annual incidence was 10.3% in 5- to 9-year-olds, 1.9% in 10- to 14-year-olds and 1.2% in the 15- to 19-year age groups, respectively. Hospitalization rates among the entire KPMCP membership were 2.6 and 2.1 per 100,000 person years for varicella and zoster, respectively. Varicella incidence in the 15- to 19-year age group was higher among African-Americans than among Caucasians. CONCLUSIONS: Varicella rates were similar in the 5- to 9- and 10- to 14-year age groups to rates from other published studies conducted in 1972 to 1978, 1980 to 1988 and 1990 to 1992; however, the rate in 15- to 19-year-olds was 2 to 4 times higher than published rates in the same age category.

Postlicensure study of varicella vaccine effectiveness in a day-care setting.

BACKGROUND: Varicella vaccine has been licensed for use in the United States since the spring of 1995. The acceptance of the vaccine and its effect on varicella incidence in children is important. AIM: To document the effectiveness of the varicella vaccine in children attending day care in 11 centers in North Carolina. METHODS: A dynamic cohort study design was used in 11 day-care centers in North Carolina. Multiple cross-sectional evaluations were performed and children were noted to be vaccinated or not and diseased or not. Vaccine effectiveness was estimated by comparing the varicella attack rate in the vaccinated with the varicella attack rate in the unvaccinated. Person time was used as the denominator for all calculations. RESULTS: During the study period February 1, 1996, to September 1, 1997, 134 cases of varicella occurred in the unvaccinated and 11 cases occurred in the vaccinated children. The attack rates in the vaccinated and unvaccinated were 2.49 and 14.66, respectively, for an overall vaccine effectiveness of 83% for mild/moderate disease. CONCLUSIONS: In the day-care setting varicella vaccine demonstrated benefit in preventing and modifying wild-type varicella disease.

Postmarketing evaluation of the safety and effectiveness of varicella vaccine.

BACKGROUND: The Oka strain of live attenuated varicella virus was licensed for use in healthy children in the United States in March, 1995. We report a postmarketing evaluation of the short term safety of this vaccine within Kaiser Permanente. METHODS: After licensure varicella vaccination was introduced into the preventive care program of the Northern California Kaiser Permanente Medical Care Program. Potential adverse events after vaccination with varicella vaccine were identified from automated clinical databases of hospitalizations, emergency room visits and clinic visits. Deaths were identified from automated clinical databases at Kaiser as well as from the State death records for California. To evaluate safety, rates of diagnosis-specific events in the risk periods were compared with the rates of such diagnosis-specific events in two self control and one historical control period. RESULTS: During the study period of April 1, 1995, to December 31, 1996, a total of 89753 adults and children received varicella vaccine. A total of 3200 relative risks were calculated, and of these 5 hospital diagnostic categories, 9 emergency visit diagnostic categories and 30 outpatient diagnostic categories demonstrated at least 1 relative risk with a P value of <0.05 in 1 or more age groups and in comparisons with 1 control period or more. The p value for these tests was not adjusted for multiple comparisons. Of these categories 14 demonstrated an increased risk either in more than 1 age group or against more than 1 comparison group. These categories included elective procedures, febrile seizure, febrile illness, well child, acute gastroenteritis, varicella, congenital anomaly, "rule out sepsis," trauma, viral syndrome, apnea, back pain, congenital valvular heart disease and vision evaluation for glasses. Of these the outcomes of elective procedure, congenital anomaly, congenital valvular heart disease, well child and vision evaluation for glasses were judged not to have a biologically plausible association with vaccination. A second diagnostic grouping included febrile illness, viral illness, febrile seizure and "rule out sepsis." In an analysis of these events which adjusted for the concomitant administration of M-M-R(II) vaccine, none of the associations was statistically associated with receipt of varicella vaccine. The diagnostic category of "rule out sepsis" still had a relative risk of 1.95 with P = 0.02. None of the children in the "rule out sepsis" category had positive bacteriologic cultures from any other normally sterile site. Because of the large number of gastroenteritis cases, we reviewed a random sample of 100 exposed and 100 unexposed cases. From this review no consistent time association or clustering of any of these events was seen in the exposed follow-up time interval. Only gastroenteritis and negative evaluations for sepsis were thought to be possibly associated with receipt of varicella vaccine. Although there was a statistically significant increased risk over the entire 30 day-period, there was no clustering of these events within the 30-day window. CONCLUSION: In this study population of 89753 children and adults, the varicella vaccine (Oka strain, Merck) appeared to have a favorable safety profile. In addition rates of varicella-like rash and of breakthrough cases were both low and consistent with the rates observed in prelicensure studies.

Partial uptake of varicella vaccine and the epidemiological effect on varicella disease in 11 day-care centers in North Carolina.

BACKGROUND: The increasing use of varicella vaccine in children attending day care has rapidly decreased the incidence of wild-type varicella disease. The herd immunity noted is significant and will have an effect on the epidemiology of natural varicella. OBJECTIVE: To monitor the change in varicella incidence in day-care attendees after the licensure of varicella vaccine. DESIGN: A prospective observational cohort study design. SETTING: Eleven private day-care centers and preschools in North Carolina participated in the study from January 1, 1995, through December 31, 1999. PARTICIPANTS: All children in the 11 centers were eligible for participation. Some participated more actively, supplying information on a regular basis. Others participated passively. Day-care personnel provided information about all cases of varicella. INTERVENTIONS: None. MAIN OUTCOME VARIABLES: The change in the incidence of varicella disease was documented as the use of varicella vaccine increased. RESULTS: Varicella vaccine coverage increased substantially from 4.4% in 1995 to 63.1% in December 1999. The vaccination rate accelerated dramatically in 1996 and 1997, leveled off in 1998, and rose again in 1999. Cumulative varicella incidence decreased from 16.74 cases per 1000 person-months in July 1996 to 1.53 cases per 1000 person-months in December 1999 in unvaccinated children. CONCLUSIONS: The varicella vaccination rate continued to increase slowly in the day-care population after an initial rapid uptake. The decrease in varicella disease is greater than the increase in varicella vaccination. This herd effect is welcome and even apparent in the unvaccinated children younger than 1 year.

Oscillations in cell morphology and redox state.

Fluctuations in the intensity of light scattered and absorbed by cells in suspension have been analysed by smoothing, periodogram and power spectrum methods to reveal oscillations attributed to changes in cell morphology and the redox state of NADH and FAD (periods 10 s to 30 min). The rhythms are themselves periodically modulated in amplitude at a similar frequency and exhibit burst characteristics. The low frequency scatter dynamics are provisionally attributed to oscillations in gross morphology and the high frequency variation to changes at the cell surface. Agents, such as insulin and transferrin, affect the dynamics. The scatter results suggest that rhythmic changes in cell morphology associated with locomotion are largely inherent in the cell and not due to periodic attachment and detachment from a surface.

Development and evaluation of a standardized questionnaire for identifying adverse events in vaccine clinical trials.

In vaccine trials, diary questionnaires or vaccination report cards (VRCs) are used extensively to collect complaints reported by subjects or guardians following vaccination. These have not been evaluated for accuracy or standardized to facilitate tolerability comparisons among vaccines.Objectives -(1) Develop standardized, age-specific VRCs for collecting self-reported adverse events (AEs) in trials; (2) Evaluate whether complaints elicited by nurse examinations or telephone interviews were missed by VRCs.Methods -Vaccine-trial databases, focus groups, experts and experienced nurses were used to develop paediatric and adolescent/adult VRCs. VRCs were evaluated at four sites. The primary outcome was subjects with AEs missed on the VRC and reported in nurse examinations (for injection-site reactions) or telephone interviews (for systemic complaints).Results -Of 855 subjects, 96.5% completed VRCs. For systemic complaints, 1.5% (12/812) reported both no complaint on VRCs and at least one complaint in telephone interviews. For injection-site reactions, 5.1% (53/1030) of injection sites had both no reaction reported on VRCs and had reactions noted by nurse examination. No missed AEs were rated as severe.Conclusion -The data suggest VRCs provide a practical and reasonably complete method of eliciting complaints following vaccination. Copyright (c) 2000 John Wiley & Sons, Ltd.

The effect of additional shots on the vaccine administration process: results of a time-motion study in 2 settings.

CONTEXT: The introduction of combination vaccines to the pediatric regimen offers the possibility of reducing the number of injections required to reach full vaccination status. Fewer injections benefit the patient/child and the parent/caregiver, and the healthcare provider may benefit from savings in personnel time associated with vaccine administration. To date, however, these savings have not been quantified. OBJECTIVE: To study the vaccine administration process in a managed care environment. STUDY DESIGN: We studied 2 settings in which vaccinations were administered: (1) a devoted injection room and (2) the examination room as part of the well-child examination. For each setting, we documented the vaccine administration process, identified vaccine-related activities, and quantified the time savings in each activity by reductions in the number of shots. PATIENTS AND METHODS: For vaccine recipients younger than 2 years, time-motion data on vaccine-related activities in 2 managed care settings were collected by a professional industrial engineering consultant. Activity time data by the number of shots administered were analyzed using linear regression adjusting for patient age. RESULTS: We observed 276 vaccination visits (137 in an examination room, and 139 in an injection room). Total nurse time associated with vaccine administration decreased by 2.4 and 1.7 minutes per shot eliminated in the examination room setting (P = .006) and in the injection room setting (P < .001), respectively. Significant time savings were realized for activities associated with vaccine preparation, vaccine injection, and administrative duties. In addition, infant crying time decreased by 1.0 and 0.4 minutes per shot eliminated in the examination room and injection room settings, respectively (P < or = .001 for both). CONCLUSIONS: Significant reductions in vaccine administration time could be achieved by eliminating injections during a well-child regimen.

Epidemiology of bacterial meningitis among children in Brazil, 1997-1998.

OBJECTIVE: To document the incidence and the descriptive epidemiology of bacterial meningitis among individuals under age 20 in a geographically defined region in Brazil during the two-year period immediately preceding the introduction of Haemophilus influenzae type b (Hib) vaccines into the national immunization program of Brazil. METHODS: Population-based epidemiological study of all cases of bacterial meningitis reported among residents of Campinas, Brazil, under age 20 (n=316,570) during the period of 1997-98, using comprehensive surveillance records compiled by the Campinas Health Department from cases reported among hospital inpatients, outpatients, emergency room visits, death certificates, and autopsy reports. RESULTS: The incidence of bacterial meningitis (n=274) was 334.9, 115 and 43.5 cases/10(5) person-years (pys) for residents of Campinas under age 1, 5 and 20, respectively. All cases were hospitalized, with an average length of stay of 12 days. Documented prior antibiotic use was 4.0%. The case-fatality rate of bacterial meningitis in individuals under age 20 was 9% (24/274) with 75% of deaths occurring in children under the age of five. The incidence of Hib meningitis (n=26) was 62.8 and 17 cases/10(5) pys in children age <1 and <5, respectively. CONCLUSIONS: The incidence of Hib meningitis in children under the age of 5 in Campinas during 1997-98 was similar to that reported in the US, Western Europe, and Israel prior to widespread Hib vaccine use in those regions. This study provides a baseline for later studies to evaluate changes in the etiology and incidence of bacterial meningitis in children after introduction of routine Hib vaccination in Brazil.

Application of the BRAT framework to case studies: observations and insights.

The BRAT Framework is a set of flexible processes and tools that provides a structured approach to pharmaceutical benefit-risk decision making in drug development and post approval settings. A work in progress, it consists of six steps that produce representations of key tradeoffs, with appropriate documentation of the rationale for decisions and the assumptions made in their development. This article describes insights, gained from case studies, into the Framework's performance in a variety of constructed benefit-risk scenarios, focusing on a hypothetical example of a triptan for migraine. The scenarios described illustrate the challenges inherent in arriving at many of the regulatory decisions, including obtaining data for matching populations for all outcomes, finding data of consistent quality, addressing correlated outcomes (e.g., elevated liver function tests and hepatitis rates), dealing with rare but serious adverse events (AEs), and understanding and making decisions based on information for many outcomes simultaneously. The Framework provides a structure for organizing, interpreting, and communicating relevant information, including heterogeneity in results and the quality and level of uncertainty of data, in order to facilitate benefit-risk decisions.

Safety and availability of dapivirine (TMC120) delivered from an intravaginal ring.

Vaginal delivery of 200 mg or 25 mg dapivirine from intravaginal rings (IVRs) was evaluated over a 7-day period in two phase 1 safety trials (IPM001 and IPM008, respectively) in a total of 25 healthy women 19 to 46 years of age. The IVR was generally safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Across both studies, dapivirine concentrations in vaginal fluids measured at the introitus, cervix, and ring area were within the mean range of 0.7-7.1 microg/ml. Mean dapivirine concentrations in vaginal and cervical tissues on day 7 were 0.3-0.7 microg/g in IPM001 and 1.5-3.5 microg/g in IPM008. Mean plasma concentrations of dapivirine were <50 pg/ml. Dapivirine from both IVRs was successfully distributed throughout the lower genital tract at concentrations >1000x the EC(50) against wild-type HIV-1 (LAI) in MT4 cells suggesting that IVR delivery of microbicides is a viable option meriting further study.

The selective toxicity of medications used in the treatment of AIDS on the CEM human leukemic CD4+ T-cell line.

Eleven medications used in the treatment of the human immunodeficiency virus or subsequent opportunistic infections were tested to determine their toxicity to the growth of the CEM line of transformed CD4+ T-cells. A selectivity ratio (IC50/EC50) for each agent against its target pathogen was calculated as an in vitro indication of the therapeutic value of that agent. Among the anti-HIV agents tested in this study, 2',3'-dideoxyinosine (ddI) had the highest in vitro selectivity ratio, 2.5 times higher than that of 3'-azido-3'-deoxythymidine (AZT). Dapsone had the highest selectivity ratio of the four agents used in the treatment of Pneumocystis carinii pneumonia that were tested. Ketoconazole had a very low selectivity ratio for Candida spp. due to its very high toxicity to CD4+T-cells.

Risk factors of HIV-1 infection among female prostitutes in Khon Kaen, Northeast Thailand.

HIV infection has increased to epidemic proportions in Thailand since 1987. There have been separate epidemics among population groups at high risk of infection and significant increases in different localities. The northeast region of Thailand has been affected by the epidemic since early 1989. The purpose of this study was to identify factors associated with HIV transmission among prostitutes during an early phase of the epidemic in the regional center of Khon Kaen. Three hundred and fifty-six prostitutes known to work in the urban area of Khon Kaen (Ampur Muang) in November 1990 were included in the study. Prostitutes were divided into two groups according to the type of place where they worked: direct prostitutes (in brothels, n = 217) and indirect prostitutes (in massage parlors, n = 139). The prevalence of HIV infection was found to be 12% among direct prostitutes and 2% among indirect prostitutes. Four variables were significantly associated with HIV infection after adjusting for confounders by logistic regression analysis: previous work in an area of high HIV prevalence, working in Khon Kaen less than one month, a low price charged for sex and using injectable contraceptives. Follow-up investigations are currently being carried out to explore in detail the association between the use of injectable contraceptives and HIV infection.

PIP: HIV infection has increased to epidemic proportions in Thailand since 1987. There have been separate epidemics among population groups at high risk of infection and significant increases in different localities. The northeast region of Thailand has been affected by the epidemic since early 1989. The purpose of this study was to identify factors associated with HIV transmission among prostitutes during an early phase of the epidemic in the regional center of Khon Kaen. 356 prostitutes known to work in the urban area of Khon Kaen (Ampur Muang) in November 1990 were included in the study. Prostitutes were divided into two groups according to the type of place where they worked: direct prostitutes (in brothels, n = 217) and indirect prostitutes (in massage parlors, n = 139). The prevalence of HIV infection was found to be 12% among direct prostitutes and 2% among indirect prostitutes. Four variables were significantly associated with HIV infection after adjusting for confounders by logistic regression analysis: previous work in an area of high HIV prevalence; working in Khon Kaen less than one month; a low price charged for sex; and using injectable contraceptives. Follow-up investigations are currently being carried out to explore in detail the association between the use of injectable contraceptives and HIV infection. (author's)

Human immunodeficiency virus infection in Mexico City. Rectal bleeding and anal warts as risk factors among men reporting sex with men.

The objectives of this study were to evaluate the frequency and determinants of rectal bleeding and the association between rectal bleeding and risk of human immunodeficiency virus (HIV) infection among homosexual/ bisexual men in Mexico City. Men who requested anonymous HIV testing at a public clinic in Mexico City and who reported engaging in any homosexual behavior were eligible to participate in this study. Trained staff collected information on demographic factors, sexual behavior, psychological states, and HIV serostatus from all consenting, eligible clients. Logistic regression modeling was used to investigate the independent effect of risk factors among 2,758 men who were tested between June 1991 and December 1992. Bleeding during anal intercourse was a common occurrence: More than one third of the men in the study reported some bleeding, and 8% reported bleeding in half or more of their intercourse episodes. The prevalence of HIV infection among bleeders was 42% as compared with 28% in nonbleeders (p < 0.0001), and the adjusted odds ratio was 1.8 (95% confidence interval (CI) 1.1-2.8) for men who bled in more than half of their anal intercourse episodes relative to nonbleeders. There was a trend of increasing HIV seroprevalence with increasing frequency of rectal bleeding (p = 0.001). Nine percent of all HIV infections and 42% of infections among frequent bleeders were attributable to rectal bleeding. Men who reported both rectal bleeding and anal warts were 3.5 (95% CI 2.1-5.8) times more likely to be HIV-infected in multivariate analysis than men reporting neither rectal bleeding nor anal warts. Determinants of rectal bleeding included older age, more education, more receptive anal intercourse than insertive intercourse, receptive digital-anal contact, anal warts, and genital ulcers. Among men reporting sex with men in Mexico City, rectal bleeding is common. It is an independent risk factor for HIV infection, and warrants attention in acquired immunodeficiency syndrome prevention efforts. Rectal bleeding that results from rupture of anal warts may be an especially effective portal of HIV transmission.

PIP: During June 1991 to December 1992, 68.8% of all men who gave informed consent for HIV testing at a public health clinic in Mexico City and for participation in this study had ever had sexual intercourse with men. The final sample size was 2758 men. The study examined the reported frequency of rectal bleeding, the determinants of rectal bleeding, and the interactions between rectal bleeding and other risk factors with HIV infection among homosexual/bisexual men. It also aimed to determine whether rectal bleeding is an independent risk factor for HIV transmission. 32.8% had HIV infection. 39% reported some rectal bleeding during anal intercourse. 8% experienced rectal bleeding during at least 50% of intercourse episodes. Overall, bleeders were more likely to be HIV infected than nonbleeders (42% vs. 28%; p 0.0001; adjusted odds ratio [AOR] = 1.8 for men who bled in more than 50% of anal intercourse episodes; AOR = 1.3 for men who sometimes bled). The odds ratios increased as the frequency of reported rectal bleeding increased (p = 0.001). Condom use during receptive anal intercourse did not affect the association between rectal bleeding and HIV infection. 9% of all HIV infections were attributable to rectal bleeding. 42% of HIV infections among bleeders were attributable to rectal bleeding. In the multivariate analysis, men with both rectal bleeding and anal warts were more likely to have HIV infection than men who had neither (67.9% vs. 27.2%; AOR = 3.5). Significant predictors of rectal bleeding were older age (i.e., =or 30) (AOR = 1.5), more education (AOR = 1.4-1.5), more receptive anal intercourse than insertive intercourse (AOR = 5.3-16.1), receptive digital-anal contact (AOR = 1.6), anal warts (AOR = 1.9), and genital ulcers (AOR = 2). These findings show that rectal bleeding is an independent risk factor for HIV infection. Rupture of anal warts is an especially effective portal of HIV transmission.

The effectiveness of Haemophilus influenzae type b conjugate vaccines in a high risk population measured using immunization register data.

The Northern Territory of Australia has had historically very high incidence rates of invasive Haemophilus influenzae type b disease in children less than 5 years of age, with the burden of disease greatest among Aboriginal infants less than 12 months. This study documents the impact of conjugate Hib vaccines introduced in 1993. Immunization rates were monitored using an existing immunization register, and case finding was done retrospectively using hospital and laboratory records. Following the vaccine introduction, the incidence fell abruptly to a seventh of its pre-vaccination level, in both Aboriginal and non-Aboriginal children. The effectiveness of PRP-OMPC (PedvaxHIB) was 97.5% and the overall effectiveness of the vaccination programme was 86.3%. The study shows Hib immunization as an effective intervention while discussing continuing needs for Hib control in high risk populations. It also illustrates the benefit of immunization registers in the evaluation of immunization programmes and assessment of vaccine effectiveness.

Fat redistribution in indinavir-treated patients with HIV infection: A review of postmarketing cases.

CONTEXT: Fat redistribution (FR) occurring alone or in association with hyperlipidemia has been associated with protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTIs); however, the relationship between FR features, relationship of FR to hyperlipidemia, and pathogenesis of FR is unknown. OBJECTIVE: To characterize the spectrum of FR, assess relationships among FR features, determine trends in occurrence of FR, and determine relationship of FR to hyperlipidemia. DESIGN: Review of postmarketing indinavir reports of FR in Merck & Co. Inc.'s database. SETTING AND PARTICIPANTS: 282 reports of FR among HIV-positive patients taking indinavir submitted through the passive postmarketing system to Merck through February 23, 1998. RESULTS: 282 FR reports were compared across 3 groups: fat accumulation (FA) only, FA with peripheral wasting (FA with PW), and peripheral wasting only (PWO). Of 282 reports, 56% (159 of 282) had FA only, 22% (63 of 282) had FA with PW, and 21% (60 of 282) had PWO. The proportions of reports of PWO was higher in men, whereas the proportion of reports of FA was higher in women. Blood lipids were provided in 93 of 282 reports; were elevated in 69 of 93, and were normal in 24 of 93 reports. Proportions of hyperlipidemia and hypertriglyceridemia reports were significantly higher in the PWO group versus FA only group (p =.024 and.003, respectively) and versus FA with/without PW groups (p =.038 and.005, respectively). Weight gain was more frequently reported in those with FA (100%) or FA with PW (68%), whereas weight loss was usually reported in those with PWO (83%). In all, 98% of patients reporting FR on indinavir for whom a concomitant drug history was available were also taking lamivudine, stavudine, or both. A higher proportion of patients reporting PWO (34 of 60; 56.7%) versus FA (42 of 159; 26.4%) only took both lamivudine and stavudine. CONCLUSIONS: Differences observed from analysis of cases in clinical features, gender, weight change, concomitant medications, and presence of hyperlipidemia among the three groups of FR cases reported to Merck suggests that PWO may be a distinct entity from other features of FR. The data suggest that certain antiretroviral combinations predispose HIV persons to development of FR.