SELECTED POSTER PRESENTATIONS

POSTER PRESENTATIONS SELECTED POSTER PRESENTATIONS The following summaries are based on posters presented at the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment, held July 13-16, 2003, in Paris, France LONG-TERM SAFETY AND EFFICACY OF TWO ANTIRETROVIRAL THERAPIES: LAMIVUDINE/ZIDOVUDINE PLUS ABACAVIR VS LAMIVUDINE/ZIDOVUDINE PLUS NELFINAVIR-ECUREUIL 2 (CNAF 3021) Based on a poster presented by Matheron S,* Livrozet JM, Boue F, Praindhui D, Goetschel A, Bougon N, on behalf of the CNAF 3021/Ecureuil 2 Study Group *Hôpital Bichat, Paris; Hôpital E. Herriot, Lyon; Hôpital Beclère, Clamart; GlaxoSmithKline, France Utilizing a single long-term visit to evaluate biologic and clinical data and HIV-1 RNA plasma viral load in patients who had completed 48 weeks of therapy in the CNAF 3007 study, the CNAF 3021 study reported here found that therapy with a lamivudine/zidovudine plus abacavir regimen was more feasible in terms of efficacy, stability, and tolerability than a regimen of lamivudine/zidovudine plus nelfinavir after a median follow-up of 3 years. The 92 subjects enrolled in CNAF 3021 between January and April 2002 were recruited from among the 155 HIV-1 infected adults who had completed 48 weeks of the CNAF 3007 study. That study, which compared the efficacy and safety of lamivudine/zidovudine plus abacavir and lamivudine/ zidovudine plus nelfinavir as first-line treatment in patients with HIV-1 who were naive to antiretroviral therapy (ART) and with plasma HIV-1 RNA below 100 000 copies/ml in 94% of cases, found that both regimens were comparable in antiviral activity at 48 weeks and that lamivudine/zidovudine plus abacavir was well tolerated. Of the 92 patients in CNAF 3021, 47 had been randomized initially to lamivudine/zidovudine plus abacavir and 45 to lamivudine/zidovudine plus nelfinavir in CNAF 3007. The remaining 63 patients who had completed 48 weeks in CNAF 3007 did not enroll in CNAF 3021 because they or the centers where they were treated refused to participate or because they were lost to follow-up. The primary objective of CNAF 3021 was to evaluate the proportion of patients achieving plasma HIV-1 RNA below 50 copies/ml after at least 2 years of treatment. The secondary objectives were to describe clinical, biologic, and hematologic data, to assess the changes since the last follow-up visit of the CNAF 3007 trial at week 48, and to determine genotypic and phenotypic protease and reverse transcriptase resistance profiles in patients with plasma HIV-1 RNA above 1000 copies/ml. In the lamivudine/zidovudine plus abacavir group, 33 of 47 patients (70%) remained on randomized treatment at week 48, and 14 of 47 patients (30%) had switched or discontinued therapy 5 because of an adverse event or biologic abnormality, 6 because of virologic failure, and 3 for other reasons. By comparison, 15 of 45 patients (33%) in the lamivudine/zidovudine plus nelfinavir group remained on randomized treatment at week 48 while 30 of 45 (67%) had switched or discontinued therapy 11 because of an adverse event or biologic abnormality, 1 because of virologic failure, 2 because of poor compliance with therapy, and 16 for other reasons. Of the patients in this group who had discontinued lamivudine/zidovudine plus nelfinavir therapy, 11 switched to lamivudine/zidovudine plus abacavir. In addition, the duration of exposure to the initial treatment was longer in the lamivudine/ S924 Vol. 3 (9B) October 2003

zidovudine plus abacavir group (149 weeks) than in the lamivudine/zidovudine plus nelfinavir group (103 weeks). The proportion of patients with HIV-1 plasma RNA below 50 copies/ml in the intent-to-treat analysis with switch included, the intent-to-treat analysis with the switch equalizing failure, and the as-treated analysis (ie, receiving randomized therapy) in both treatment groups is shown in the Table. Genotypic and phenotypic protease and reverse transcriptase resistance was seen in 11 patients with viral loads above 1000 copies/ml, with 4 patients showing reverse transcriptase mutations associated with resistance, 3 patients showing protease mutations, and 4 patients showing mutations for both. Seven patients with reverse transcriptase or protease resistance were taking randomized therapy with lamivudine/zidovudine plus nelfinavir, and 4 were taking lamivudine/zidovudine plus abacavir. At the CNAF 3021 visit, randomized treatment was continued in 2 patients taking lamivudine/zidovudine plus nelfinavir and in 1 patient taking lamivudine/zidovudine plus abacavir, and was discontinued in the remaining 8. Cholesterol, triglycerides, glucose, and signs of lipodystrophy were also evaluated at the CNAF 3021 visit. There was a slight decrease in cholesterol in the lamivudine/zidovudine plus abacavir group and a slight increase in cholesterol in the lamivudine/zidovudine plus nelfinavir group. No difference was noted between the groups in the median change in triglyceride and glucose levels, and no major difference was seen in the proportion of patients with signs or symptoms of lipodystrophy, although there was a trend toward less lipoatrophy Table. Proportion of Patients with HIV-1 Plasma RNA <50 copies/ml Lamivudine/Zidovudine Analysis + Abacavir + Nelfinavir Intent to treat (switch included) 76% 71% Intent to treat (switch = failure) 55% 24% As-treated (receiving randomized treatment) 79% 69% in the lower limbs in patients receiving lamivudine/zidovudine plus abacavir. The study investigators concluded that in the population studied (ie, HIV-1 infected adults with plasma HIV-1 RNA <100 000 copies/ml in most cases achieving plasma HIV-1 RNA <50 copies/ml after at least 2 years of treatment) and over a median follow-up of 3 years, the efficacy, stability, and tolerability of longterm treatment are more feasible with the triple-nucleoside regimen of lamivudine/zidovudine plus abacavir than with the double nucleoside/protease inhibitor regimen of lamivudine/zidovudine plus nelfinavir. HIV RISK FACTORS AND DEPRESSION IN PATIENTS WITH HIV ALONE OR IN COMBINATION WITH ALCOHOLISM Based on a poster presented by Buss JC,* Kemper CA,* Sassoon SA, Rosenbloom MJ, Deresinski S,* Sullivan EV, Pfefferbaum A *Santa Clara Valley Medical Center, San Jose, California; Neuroscience Program, SRI International, Menlo Park, California; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California As the results of this study indicate, persons with HIV infection and high alcohol use are more likely to use or abuse stimulants and intravenous drugs, have a lifetime major depression, have hepatitis C coinfection, and have significantly lower psychosocial functioning scores compared with persons with either high alcohol use or HIV alone. Accordingly, the study investigators recommend that patients with HIV be aggressively screened for alcohol use/dependence, drug use, depression, and other mental health problems, as well as hepatitis C coinfection to maximize the success of medical treatment. The ongoing longitudinal study, supported by a grant from the National Institute on Alcoholism and Alcohol Abuse, is recruiting subjects with and without HIV-1 and/or alcoholism from outpatient clinics and treatment centers in the San Francisco Bay Area. A substantial proportion of the subjects recruited thus far were from underserved and high-minority neighbor- Advanced Studies in Medicine S925

hoods. Those with schizophrenia, bipolar disorder, neurologic disease not related to alcohol use or HIV, drug abuse or dependence within the previous 3 months, and a Karnofsky score below 70 were excluded, as were those who were unable to undergo magnetic resonance imaging (MRI) scanning. Although the ongoing study includes MRI scans and neuropsychological assessment, only the clinical and behavioral characteristics of 74 subjects at baseline are reported here. Of the 74 subjects, 22 were HIV-positive with high alcohol use, 20 were HIV-positive with low alcohol use, 17 were HIV-negative with high alcohol use, and 15 were HIV-negative with low alcohol use (controls). Clinical assessments included the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Disorders (ie, Axis I psychiatric diagnosis, alcohol dependence/abuse, drug dependence/ abuse, Global Assessment of Functioning [GAF] score to assess social, psychological, and occupational level of functioning); Beck Depression Inventory score; demographic characteristics, such as years of education, HIV risk behaviors, history of drug use, and family history of alcohol use; and various laboratory studies. Subjects with HIV and high alcohol use had the highest use of intravenous drugs and stimulants, whereas those with HIV and low alcohol use reported the highest incidence of men having sex with men. Subjects with HIV and high alcohol use also had the highest incidence (59%) of hepatitis C coinfection. CD4 cell counts and viral loads were similar in both groups of HIV-positive subjects. Of those with HIV and high alcohol use, 55% were taking antiretroviral therapy, compared with 75% of those with HIV and low alcohol use. Of those taking therapy, only 33% in the HIV/high-alcohol-use group and 47% in the HIV/low-alcohol-use group had viral loads below 400 copies/ml and only 8% and 13%, respectively, had levels below 50 copies/ml. Significantly more subjects in the HIV/high-alcohol-use group met the DSM-IV criteria for drug dependence or abuse and lifetime major depression compared with the HIV/low-alcohol-use and control groups, but not with the HIV-negative/high-alcoholuse group, which also had a high incidence of drug dependence and lifetime major depression. All groups self-reported mild levels of current depression on the Beck Depression Inventory compared with controls, but the incidence was highest in those with HIV and high alcohol use, followed by those with HIV and low alcohol use and those with no HIV but high alcohol use. In addition, GAF scores were significantly lower in subjects with HIV and high alcohol use compared with subjects in the other groups. Although the sample size is small, the study investigators note that the clinical implications of the findings that alcoholism, depression, and hepatitis C coinfection may negatively affect the success of antiretroviral therapy and complicate the medical management of HIVinfected individuals cannot be ignored. FACTORS ASSOCIATED WITH PERIPHERAL NEUROPATHY IN THE HIV OUTPATIENT STUDY COHORT (HOPS) Based on a poster presented by Lichtenstein KA,* Armon C, Baron A, Moorman A, Wood K, Holmberg SD *Rose Medical Center, Denver, Colorado; University of Colorado Health Sciences Center, Denver; Cerner Corporation, McLean, Virginia; Division of HIV/AIDS Prevention, Surveillance and Epidemiology, Centers for Disease Control and Prevention, Atlanta, Georgia Data from the HIV Outpatient Study (HOPS) cohort of 2178 patients with HIV-1 infection indicate that increasing age, diabetes mellitus, white race, nadir CD4 count, and other measures of HIV disease severity are the strongest predictors of peripheral neuropathy. HOPS data also indicate that the association of antiretroviral therapy with peripheral neuropathy is more likely in patients with advanced HIV-1 disease and that reversal of immune deficits in response to antiviral therapy may reduce the risk of peripheral neuropathy after the first year of treatment. In addition, the data show that all classes of antiretroviral drugs, including those that are associated with peripheral neuropathy during the first year of therapy, reduce the risk of peripheral neuropathy below the expected incidence after 3 years of use in patients who do not develop peripheral neuropathy in the first year of treatment. Of the 2178 patients with a complete set of measurable clinical parameters, 490 (22.5%) had a clin- S926 Vol. 3 (9B) October 2003

ical diagnosis of peripheral neuropathy defined as pain, tingling, and numbness in the hands and/or feet due to HIV infection, antiretroviral therapy, or other or unknown causes. In a logistic regression analysis of nondrug risk factors, age older than 40 years, diabetes, white race, nadir CD4 counts below 50 cells/mm3 and 50 to 199 cells/mm3, and a first viral load measurement above 10 000 copies/ml were found to be statistically significant for peripheral neuropathy. Although initial use of any of 3 nucleoside analogues (stavudine, didanosine, zalcitabine) or 4 protease inhibitors, (indinavir, ritonavir, nelfinavir, saquinavir) was associated with peripheral neuropathy in the first year of treatment, a logistic regression analysis of drug risk factors demonstrated that if peripheral neuropathy did not occur in the first year, continued use of these same drugs was associated with an absence of risk against peripheral neuropathy after 3 or more years of use. For example, the adjusted odds ratio of developing peripheral neuropathy on stavudine during the first year of treatment was 2.38, but it dropped to 1.06 during the second year, 0.70 during the third year, and 0.29 after 3 years (P <.001). Similarly, the adjusted odds ratio of developing peripheral neuropathy on indinavir during the first year of treatment was 2.39, but it dropped to 1.39, 0.61, and 0.19, respectively, for the same time periods (P <.001). MANAGING PSYCHIATRIC MANIFESTATIONS OF HIV INFECTION Based on a poster presented by Zuniga JM, Smith B International Association of Physicians in AIDS Care (IAPAC), Chicago, Illinois The findings of a recent physician/patient survey regarding the prevalence and management of neurologic and psychiatric manifestations of HIV infection and treatment suggest that increased awareness of the psychiatric, neurologic, and pharmacologic issues associated with HIV infection and their appropriate management can lead to better overall clinical management. Utilizing telephone and Internet-facilitated surveys of physicians who treat HIV-infected patients to examine current practices regarding specific psychiatric manifestations of HIV infection, the study investigators found that 80% of the 153 physicians surveyed considered a patient s mental health as a high priority in making treatment decisions. However, when the investigators surveyed 235 patients who were recruited from The Body Web site and who indicated that they had been HIV positive for 15 to 20 years, they found that 62% of the patients reported never being consulted by their physicians about mental health issues. The most common psychiatric symptoms reported by the patients were depression (72%), anxiety (65%), insomnia (48%), lethargy (43%), irritability (41%), impaired concentration (40%), and mood swings (40%). These symptoms reflect the variety of emotional, cognitive, and neurologic disturbances associated with HIV infection, as well as their diverse etiologies, including premorbid psychiatric disorders, psychological stress, and the direct effects of HIV, opportunistic infections, and specific antiretroviral agents on the central nervous system. The most frequent medical intervention was the prescription of antidepressant drugs, which was done by 64% of the physicians surveyed. Although 75% of the physicians surveyed believed that specific antiretroviral agents (particularly efavirenz, which was cited by 47%) were the leading cause of most common psychiatric symptoms in patients with HIV infection, only 57% recommended that patients switch agents in their antiretroviral regimens because of these symptoms. With these discrepant findings in mind, the study investigators recommended that physicians who treat HIV-infected patients address psychiatric, neurologic, and pharmacologic issues through counseling and referrals to mental health professionals to help patients cope with depression/anxiety and otherwise deal with the transient psychiatric effects of some antiretroviral agents. They also recommended strategic prescribing to minimize the occurrence of antiretroviral-related psychiatric symptoms that cannot be managed, and the application of mental health screening and assessment tools to better diagnose and monitor patient response. Advanced Studies in Medicine S927

PROSPECTIVE STUDY OF HYPERLIPIDEMIA IN ART- NAIVE SUBJECTS TAKING ABACAVIR/LAMIVUDINE/ ZIDOVUDINE, LAMIVUDINE/ZIDOVUDINE PLUS NELFINAVIR, OR STAVUDINE PLUS LAMIVUDINE PLUS NELFINAVIR Based on a poster presented by Kumar P,* Rodriguez- French A, Thompson M, Tashima K, Wannamaker P *Georgetown University Medical Center, Washington, DC; San Fernando Hospital, Panama City, Panama; AIDS Research Consortium of Atlanta, Atlanta, Georgia; The Miriam Hospital, Providence, Rhode Island; GlaxoSmithKline, Research Triangle Park, North Carolina The 96-week study reported here has demonstrated that a triple-nucleoside regimen of abacavir/ lamivudine/zidovudine does not increase levels of total and low-density lipoprotein (LDL) cholesterol compared with 2 regimens containing 2 nucleosides and the protease inhibitor nelfinavir. This finding is noteworthy not only because of its favorable effect on cholesterol levels, but also because it was seen in a diverse study population that reflects current trends in HIV cases. One half of the 254 patients in this study were women, 40% were African American, 37% were Hispanic, 21% were Caucasian, and approximately two thirds were heterosexual and one third homosexual. The Phase IV, open-label, randomized, parallelgroup study included patients who were naive to antiretroviral therapy, were 18 years of age or older, and had viral loads between 1000 and 200 000 copies/ml and CD4 lymphocyte counts greater than 50 cells/mm3 at screening. Patients were stratified by viral load ( 1000 100 000 copies/ml and >100 000 200 000 copies/ml) and then randomized to one of 3 treatment regimens for 96 weeks: abacavir/lamivudine/zidovudine (n = 85), lamivudine plus nelfinavir (n = 88), or stavudine plus lamivudine plus nelfinavir (n = 81). Mean baseline characteristics (age, viral load, CD4 cell count, and LDL and total cholesterol levels) were similar in all groups, as were the percentages of patients who were homosexual, heterosexual, and intravenous drug users. At 96 weeks, however, total and LDL cholesterol levels were significantly lower in the abacavir/lamivudine/zidovudine group than in the groups receiving the regimens containing nelfinavir (P <.001). Significantly more patients in the groups receiving nelfinavir had LDL cholesterol levels above 130 mg/dl or above 160 mg/dl (P.03) and total cholesterol levels above 200 mg/dl (P.005) compared with patients receiving abacavir/lamivudine/zidovudine. These levels exceed the current lipid intervention guidelines established by the National Cholesterol Education Program. High-density lipoprotein cholesterol levels remained similar to baseline levels in all groups. Elevated triglyceride and lactate levels, however, were most commonly seen in the group receiving stavudine plus lamivudine plus nelfinavir. CD4 lymphocyte response was similar with all regimens, as was the pattern of viral RNA response in patients with viral loads >100 000 to 200 000 copies/ml. Although patient withdrawal was high in the study as a whole, fewer patients in the abacavir/ lamivudine/zidovudine group withdrew because of efficacy or safety concerns. EFFICACY OF ABACAVIR/LAMIVUDINE/ZIDOVUDINE AND TENOFOVIR AS HAART FOR HIV-INFECTED PATIENTS WITH CURRENT OR UNDERLYING REVERSE TRANSCRIPTASE RESISTANCE Based on a poster presented by Ruane P,* Luber A, Gaultier C,* Swaminathan S,* Stryker R,* van Kempen A, Lanier R *Tower ID Medical Associates, Los Angeles, California; GlaxoSmithKline, Research Triangle Park, North Carolina As demonstrated in this small, prospective, observational study, abacavir/lamivudine/zidovudine plus tenofovir represents a viable treatment option for HIVinfected patients with suspected or documented M184V mutations and fewer than 3 thymidine analog mutations (TAMs). The study involved 20 men who had been infected with HIV for a median of 6.5 years (range, 3 11 years) and treated with a median of 5.5 antiretroviral S928 Vol. 3 (9B) October 2003

regimens (range, 2 10 regimens) before they switched to abacavir/lamivudine/zidovudine plus tenofovir because of virologic failure, simplification of therapy, or lipid issues. Patients were included in the study if they were 18 years of age or older, on a stable highly active antiretroviral therapy (HAART) regimen for more than 12 weeks, currently experiencing viral breakthrough with a viral load below 10 000 copies/ml or had a nondetectable viral load but required a change of therapy for simplification and/or lipid abnormalities, had genotypic assay results showing current or archived M184V mutations with or without 1 to 2 TAMs, had no prior therapy with abacavir or tenofovir or K6SR or L74V mutations to these drugs, and had adequate hepatic, renal, and hematologic function. Patients were also included in the study if resistance was suspected on the basis of treatment history. At the time of the switch, 2 of the men were on single protease inhibitor (PI) HAART, 2 were taking dual PI HAART, 13 were on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based HAART, and 3 were on other HAART regimens. With regard to resistance, 10 of the men had documented M184V mutations, 3 had documented TAMs, 11 had HIV replication with prior dual nucleoside reverse transcriptase inhibitor therapy, and 6 had HIV replication with HAART. After the switch, patients were followed up at weeks 2, 4, 8, 16, and 24. Changes in viral load, CD4 cell counts, fasting lipid values, and various laboratory tests for safety parameters were noted at each time point and evaluated as changes from baseline. Viral failure was defined as a documented viral load measurement above 400 copies/ml on 2 separate visits within 4 weeks of each other. All viral failures were genotyped. Nondetectable viral load assessments were evaluated as below 400 copies/ml and below 75 copies/ml. Of the 3 patients who were switched because of virologic failure, 2 achieved viral loads below 75 copies/ml, and 1 achieved a viral load below 400 copies/ml after the switch to abacavir/lamivudine/zidovudine plus tenofovir. Of the 17 patients who were switched for simplification of therapy and/or lipid abnormalities, only 2 experienced virologic breakthrough, both at week 4, with M184V mutations and multiple TAMs presumably due to resurgence of previously archived mutants rather than the development of new mutations. Among patients switched for lipid abnormalities, cholesterol and triglyceride levels decreased after initiation of abacavir/lamivudine/zidovudine plus tenofovir, with a greater percentage of patients achieving the target levels for cholesterol and triglycerides recommended by the National Cholesterol Education Program in its most recent report. No unusual or unexpected adverse events were noted during the study. The most frequently reported side effects were mild headache and nausea. No patient discontinued the study regimen because of an adverse drug event, and no documented or suspected hypersensitivity reaction to abacavir was observed. ANEMIA PREVALENCE AMONG HIV PATIENTS: ANTIRETROVIRAL THERAPY AND OTHER RISK FACTORS Based on a poster presented by Wills TS,* Nadler JP,* Somboomwit C,* Vincent A,* Leitz G, Marino K, Naik E,* Powers S,* Khan N,* Almyroudis N,* Laartz B* *Department of Medicine, University of South Florida, Tampa, Florida; Ortho Biotech Products LP, Bridgewater, New Jersey As demonstrated in this study of 758 patients with HIV infection, anemia (hemoglobin 12.5 g/dl) is still prevalent in this population. In determining the prevalence of anemia in this single-site public health center sample (Hillsborough County Health Department in southern Florida), the investigators also evaluated the association of anemia with the use of highly active antiretroviral therapy (HAART) and identified several predictors of anemia in these patients. The overall prevalence of anemia in this sample was 30.3%, considerably higher than the 22% reported in 10 000 HIV-infected individuals by Creagh et al at the 40th Annual Meeting of the Infectious Disease Society of America in October 2002. The prevalence was even higher in the 228 women in the study (54%) than in the 530 men Advanced Studies in Medicine S929

(20.2%), in patients with CD4 cell counts below 200 cells/mm3 (38.6% vs 12.2% in patients with CD4 cell counts 500 cells/mm3), and in patients with viral loads greater than 30 000 copies/ml (37.5% vs 16% in patients with viral loads <500 copies/ml). In addition, multivariate analysis revealed that the risk of anemia was significantly higher (P =.0011 to P =.0001) in black patients, women, older patients, those with advanced HIV disease, and those on HAART regimens containing zidovudine. RATE OF EMERGENCE OF THYMIDINE ANALOG RESISTANCE MUTATIONS (TAMS) IN PATIENTS MAINTAINED ON THYMIDINE ANALOGS DESPITE VIROLOGIC FAILURE Based on a poster presented by Goetz MB,* Ho P,* McMillan G, St. Clair M, McClernon D, O Brien WA *University of California Los Angeles Veterans Affairs of Greater Los Angeles Health Care System; GlaxoSmithKline, Research Triangle Park, North Carolina; University of Texas Medical Branch, Galveston Prompted by concerns that multiple resistance mutations would emerge unless therapy were changed in patients who developed moderate virologic failure and by the possibility that the emergence of thymidine analog mutations (TAMs) might be affected by the presence of the M184V resistance mutation, the investigators involved in this small retrospective study compared the emergence of TAMs and major protease inhibitor (PI) mutations in 14 patients with M184V mutations who remained on a stable thymidine analog-based regimen despite virologic failure. They found that major and minor PI mutations emerged more often and more rapidly compared with TAMs or other nucleoside reverse transcriptase inhibitor (NRTI) mutations. Eligibility criteria for the study were adherence to a stable thymidine analog based highly active antiretroviral therapy (HAART) regimen containing a single PI despite virologic failure, less than 2 TAMs at initial virologic failure, and the presence of M184V mutations during virologic failure. Of the 14 eligible patients, 7 were treatmentnaive, 8 received indinavir, and 6 received nelfinavir. The mean follow-up after virologic failure was 964 ± 527 days, and the mean number of genotypes per patient during virologic failure was 4.8. Mean CD4 counts were 216 cells/mm3 prior to HAART, 255 cells/mm3 at the initiation of the failing regimen, 375 cells/mm3 at the time of virologic failure, and 491 cells/mm3 at the end of follow-up. Mean log viral loads at each of these time points were 4.98, 4.65, 3.78, and 4.00, respectively. Twelve of the 14 patients had no TAMs in the first genotype during virologic failure. New TAMs emerged in 4 patients in a mean of 594 days after virologic failure, and major PI mutations emerged in 10 patients in a mean of 356 days after virologic failure. In no patient did the first major PI mutation arise after the first TAM. After 600 days of virologic failure, new TAMs emerged in 17% of patients, and new major PI mutations emerged in 61% (P <.02 compared with TAMs). Other than the 62V mutation, which developed in 3 patients, no other NRTI mutations emerged. However, 35 minor PI mutations emerged in 13 patients. In light of their findings, the study investigators concluded that further study is warranted regarding the ability to generalize the findings of the discrepant emergence of new TAMs and major PI mutations during virologic failure, its possible association with specific treatment or resistance mutations, and its underlying mechanisms. S930 Vol. 3 (9B) October 2003