Indinavir Group Research Articles

The changes in bone organic and inorganic matrix in newborn rats after maternal application of antiretroviral agents: Indinavir and zidovudine.

This work presents results concerning influence of indinavir (protease inhibitor, PI(1)) and zidovudine (nucleoside and nucleotide inhibitor of reverse transcriptase, NRTI) administered to pregnant Wistar rat females on organic and mineral constituents of bones and teeth (mandibles, skulls, tibiae, femurs, and incisors) of their offspring at the age of: 7, 14, and 28 days studied by means of induced laser and X-ray fluorescence spectroscopy supported by digital radiography. Influence of indinavir administered to pregnant female rats on bone of their offspring revealed mainly in changes of mineral concentration: lowered Ca concentration and disturbances of trace elements. Zidovudine influenced organic matter more than inorganic matrix which was seen in enhancement of LIF fluorescence. However, there was also an unexpected increase of bone density for rats from zidovudine group, unlike indinavir group, observed. Our studies suggest that studied antiretroviral agents given to pregnant women, may have different destructive impact on bone state of their offspring in the first period of life. Maternal administration of zidovudine may delay development of organic matrix, while indinavir may have adverse effects on inorganic structure.

Investigation of microstructure of bone tissue in mandibles of newborn rats after maternal treatment with antiretroviral drugs

High-resolution imaging has become a powerful tool for measurements in clinics, laboratory and animal studies, etc. In the present study, we aimed to investigate age related changes in bone development, and the effect of two antiretroviral agents (zidovudine and indinavir), which were administered during pregnancy, on the microstructure and bone mineral density (BMD) in newborn rats (7-, 14- and 28-day-old), with the use of X-ray microcomputed tomography (XMT). Fifty-four mandible bones were collected and divided into 3 groups: group 1 and 2: newborns after maternal treatment of zidovudine and indinavir respectively, group 3: control animals. The specimens were XMT scanned with the resolution of 7μm and with a density phantom. Histomorphometric parameters and BMD were calculated to assess bone development depending on the administered drug. A statistical analysis was carried out to compare the differences among the control, zidovudine and indinavir groups. The analysis of the microstructure revealed disturbances in the development of the bone tissue in newborn rats. Indinavir seems to have a greater impact on bone microstructure than zidovudine.

Immune Reconstitution in Severely Immunosuppressed Antiretroviral-Naive HIV Type 1-Infected Patients Using a Nonnucleoside Reverse Transcriptase Inhibitor-Based or a Boosted Protease Inhibitor-Based Antiretroviral Regimen: Three-Year Results (The Advanz Trial): A Randomized, Controlled Trial

Late diagnosis of HIV-1 infection is quite frequent in Western countries. Very few randomized clinical trials to determine the best antiretroviral treatment in patients with advanced HIV-1 infection have been performed. To compare immune reconstitution in two groups of very immunosuppressed (less than 100 CD4(+) cells/microl), antiretroviral-naive HIV-1-infected adults, 65 patients were randomly assigned in a 1:1 ratio to receive zidovudine + lamivudine + efavirenz (group A, 34 patients) or zidovudine + lamivudine + ritonavir-boosted indinavir (group B, 31 patients). The median (interquartile range) CD4(+) cell increase after 12 and 36 months was +199 (101, 258) and +299 (170, 464) cells/microl in the efavirenz arm and +136 (57, 235) and +228 (119, 465) cells/microl in the ritonavir-boosted indinavir arm (p > 0.05 for all time points). The proportion (95% confidence interval) of patients achieving HIV-1 RNA levels under 50 copies/ml was significantly greater in the efavirenz arm at 3 years by the intention-to-treat analysis [59% (41%, 75%) vs. 23% (10%, 41%)], whereas no differences were found in the on-treatment analysis. Immune activation (CD8(+)CD38(+) and CD8(+)CD38DR(+) T cells) was significantly lower for the efavirenz arm from month 6 to month 24. Adverse events were more frequent in the ritonavir-boosted indinavir arm. Almost all cases of disease progression and death were observed in the first year of treatment, with no significant differences between the two arms (p = 0.79 by the log-rank test). At 1 and 3 years, the immune reconstitution induced by an efavirenz-based regimen in very immunosuppressed patients was at least as potent as that induced by a ritonavir-boosted protease inhibitor-based antiretroviral regimen.

Efavirenz versus indinavir chez les patients naïfs infectés par le VIH-1 à Abidjan (Côte d’Ivoire)

Objective The authors had for aim to compare the therapeutic efficiency and tolerance of 2 NRTI + efavirenz (EFV) versus 2 NRTI + indinavir (IDV) in HIV infected adults in Abidjan. Methods A retrospective and multicentric study was made on 327 HIV-1 naive patients, 142 in the EFV group and 185 in the IDV group followed in Abidjan from November 1998 to December 2003. The analysis concerned clinical advents (opportunistic infections) and immunovirological parameters (CD4, viral load). Patients received 2 NRTI such as AZT + 3TC or D4T + 3TC combined either with EFV or IDV. The principal judgement criterion was therapeutic failure. We assessed the percentage of patients with undetectable viral load and the frequency of grade 3–4 adverse effects after 24 months of follow-up. Results Clinical improvement of patients’ state and regression of opportunistic infections were identical in the two groups. The average gain of CD4 was superior to 177 in EFV versus + 219 in IDV ( p = 0.004). The percentage of patients with undetectable viral load was 66% for EFV versus 59% for IDV ( p = 0.04). The frequency of adverse effects was more elevated with EFV than IDV, 39% versus 23% ( p = 0.002) initially, but seemed to decrease later. Conclusion HAART with EFV is at least as efficient as with IDV in terms of reduction of viral load and increased CD4 count and is an excellent low-cost first line treatment.

Efficacy and tolerability of long-term efavirenz plus nucleoside reverse transcriptase inhibitors for HIV-1 infection

To compare the long-term efficacy and tolerability of two efavirenz-containing regimens with those of an indinavir-containing regimen in the initial use of HAART. HIV-1-infected patients (N = 1266) were randomly assigned to receive one of three regimens: efavirenz, zidovudine plus lamivudine, n = 422; efavirenz plus indinavir, n = 429; or indinavir, zidovudine plus lamivudine, n = 415. Entrance criteria included baseline viral load greater than 10 000 copies/ml HIV-1 RNA, CD4 cell count 50 cells/mul or greater, and no previous use of lamivudine, any non-nucleoside reverse-transcriptase inhibitor or protease inhibitor. The primary endpoint was the proportion of patients (response rate) in each regimen with a viral load under 400 copies/ml at 168 weeks of treatment. Response rates at 168 weeks were 30% in the indinavir, zidovudine, lamivudine group, 48% in the efavirenz, zidovudine, lamivudine group (P < 0.0001, difference estimate; 97.5% confidence interval (CI) 18.5; 10.9, 26), and 40% in the efavirenz plus indinavir group (P = 0.0018, difference estimate; 97.5% CI 10.2; 2.9, 17.6). Median CD4 cell counts increased above respective baselines by 292 cells/mul (efavirenz, zidovudine, lamivudine and indinavir, zidovudine, lamivudine) and 300 cells/mul (efavirenz plus indinavir). Total discontinuations were 54% (efavirenz, zidovudine, lamivudine), 63% (efavirenz plus indinavir), and 69% (indinavir, zidovudine, lamivudine) of which 13, 12 and 26%, respectively, were caused by adverse events. No new or unexpected increases in the rates or severity of adverse events occurred from long-term treatment with efavirenz-containing regimens. Long-term HIV therapy with efavirenz-containing regimens, particularly efavirenz, zidovudine, lamivudine, provides significantly greater antiviral activity and tolerability than a regimen of indinavir, zidovudine plus lamivudine.

Comparison of Two Reduced-Dose Regimens of Indinavir (600 Mg Vs 400 Mg Twice Daily) and Ritonavir (100 Mg Twice Daily) in Healthy Volunteers (Coredir)

To assess the pharmacokinetics and tolerability of reduced dosages of twice daily indinavir (IDV) boosted by low-dose ritonavir (RTV) in healthy volunteers. Pharmacokinetics and tolerability of IDV/RTV twice daily (600/100 mg and 400/100 mg) were assessed in a randomized crossover design in 16 healthy volunteers. Each dosage was taken twice daily for 2 weeks before 12 h pharmacokinetics were obtained. Sixteen subjects were included, with a mean age +/- SD of 30 +/- 4 years; seven female, nine male. Fifteen subjects completed the study. After dose reduction of IDV AUC, Cmax and Cmin decreased significantly. In the 400 mg group three out of 15 subjects had IDV levels below 0.10 mg/l vs none in the 600 mg group. All subjects reported mild to moderate side effects throughout the study period, which were more severe in the 600 mg group (mostly renal, dry skin/lips, paresthesias/oral discomfort). In the 600 mg group four subjects reported dysuria and one subject discontinued because of flank pain, whereas two subjects reported dysuria and no subject discontinued in the 400 mg group, respectively. Eight subjects developed crystalluria without a significant difference between both groups. No significant change in serum creatinine was observed. IDV/RTV 400/100 mg twice daily resulted in significant lower IDV exposure, with three out of 15 subjects revealing Cmin values below the recommended threshold for wild-type virus of 0.10 mg/l. Tolerability, however, was lower in the 600 mg IDV group. Therapeutic drug monitoring in the individual patient appears to be necessary to guarantee appropriate drug levels and simultaneously minimize toxicity.

Differences in Durability of Treatment with Initial PI-Based Regimens

The durability of virologic response to antiretroviral therapy is dependent on the potency, tolerability, and adherence level of the regimen. In a prospective, nonrandomized cohort study, we compared the treatment outcome of a nelfinavir-based highly active antiretroviral therapy (HAART) regimen with that of an indinavir-based regimen, over 1 year of routine clinical practice. Information was derived from 134 treatment-naïve HIV-1-infected patients initiated on triple therapy with either nelfinavir (n = 44) or indinavir (n = 90). The proportions of patients achieving a virological response were similar between treatment groups (>1 log10 reduction in HIV RNA at 3 months in 95% of patients taking nelfinavir and 88% taking indinavir; HIV RNA <50 copies/mL after 1 year in 79% and 69% of patients, respectively). Predicting factors for 1-year virological suppression were initial virological response (p = .02) and adherence >90% (p = .0001). Over 90% adherence was achieved in 70% of patients taking nelfinavir compared with 41% of those taking indinavir (p = .01). The probability of remaining on the initial protease inhibitor (PI) after 12 months was 77% in the nelfinavir group and 66% in the indinavir group, with the median time to changing treatment being 519 days and 462 days, respectively. Gastric intolerance and nephritic colic were the most common reasons for changing therapy in the indinavir group. In the clinical setting, HAART based on initial nelfinavir and indinavir therapy was associated with similarly good virological and immunological suppression at 1 year, however, nelfinavir-based treatment was associated with a longer durability, probably due to a better adherence and tolerance pattern.

Saquinavir: a review of its use in boosted regimens for treating HIV infection.

Protease inhibitor boosting involves concurrent administration of a protease inhibitor, such as saquinavir, plus a potent inhibitor of cytochrome P450 (CYP) 3A4, usually ritonavir in subtherapeutic doses. Since protease inhibitors are extensively metabolised by CYP3A4, this results in a marked increase in systemic exposure of saquinavir or other protease inhibitors boosted by ritonavir. As with traditional protease inhibitor regimens, boosted regimens are typically used in combination with nucleoside reverse transcriptase inhibitors (NRTIs). In protease inhibitor-experienced and -naive patients with HIV infection, twice-daily and once-daily boosted saquinavir regimens achieved good rates of viral suppression, improved CD4+ cell counts and were generally well tolerated in clinical trials. Encouraging results have also been reported in a number of small studies in heavily pretreated HIV-infected patients who received salvage therapy comprising double-boosted regimens of saquinavir plus lopinavir with subtherapeutic doses of ritonavir, along with other agents. The largest clinical trials have been multicentre, randomised comparisons of twice-daily boosted saquinavir versus twice-daily boosted indinavir (MaxCmin1) or lopinavir (MaxCmin2) regimens. In the MaxCmin1 study, >90% of patients in both groups had an undetectable viral load (<400 copies/mL) after 48 weeks of therapy in the on-treatment analysis. However, viral suppression was achieved in significantly more saquinavir than indinavir recipients in the intention-to-treat analysis, which appeared to be due to the significantly greater percentage of patients in the indinavir group who switched from randomised therapy because of adverse events. Interim 24-week results of the MaxCmin2 trial indicate that 90% of patients in both groups combined had plasma HIV RNA levels <400 copies/mL; final results at 48 weeks will report data separately for the boosted regimens of saquinavir and lopinavir. Boosted protease inhibitor regimens (including two NRTIs) are recommended as a first-line option in current HIV treatment guidelines and are used extensively in clinical practice. The convenient administration schedule and good pharmacokinetic profile associated with boosted saquinavir regimens have the potential to increase adherence to therapy and improve antiretroviral effects through increased drug exposure. Twice-daily boosted saquinavir is one of the most extensively evaluated boosted protease inhibitor regimens and has been shown to have good efficacy on surrogate markers of HIV disease as well as significant tolerability advantages over boosted indinavir. Once-daily boosted saquinavir regimens may be most suitable for HIV-infected patients with busy lifestyles and those who would benefit from directly observed therapy.

Stable or increasing bone mineral density in HIV-infected patients treated with nelfinavir or indinavir.

To determine the factors contributing to changes in bone mineral density (BMD) over time in HIV-infected patients receiving highly active antiretroviral therapy (HAART). Analyses of lumbar spine BMD in 183 male Caucasian participants in the Western Australian HIV Cohort study, comprising a longitudinal analysis of data from 54 patients on stable HAART regimens, and a cross-sectional analysis comparing data from 131 protease inhibitor (PI)-treated patients and 52 PI-naive (including 28 antiretroviral treatment-naive) patients. Average lumbar spine BMD remained stable or increased over the time frame considered. Although there was no evidence of a change of average BMD over time in patients receiving nelfinavir (P = 0.92), there was evidence of increasing bone density in the indinavir group (average increase, 0.31 z-score per year; P < 0.001). Lower initial z-scores in the longitudinal analysis were significantly associated with lower pre-HAART BMI (P = 0.003), consistent with results of the cross-sectional analysis in which lowest BMI prior to initial dual X-ray absorptiometry scan was associated with decreased BMD (P = 0.02, overall group). Although PI therapy was also associated with decreased BMD in a univariate analysis of the cross-sectional data (P = 0.04), this effect was abrogated in a multiple linear regression analysis (P = 0.11) with lowest BMI remaining significant (P = 0.04). We found no evidence, overall, of accelerated bone loss in patients treated with nelfinavir- or indinavir-containing HAART regimens, and propose that indinavir therapy may be associated with an increase in bone mineral density over time. Pre-HAART BMI was an independent and powerful determinant of an individual's initial z-score in the longitudinal analysis, and adjustment for this effect in a cross-sectional analysis abrogated the association between PI therapy and decreased lumbar spine z-score.

A Randomized Trial Comparing the Introduction of Ritonavir or Indinavir in 1251 Nucleoside-Experienced Patients with Advanced HIV Infection

ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation-of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4+ cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4+ cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events).

Saquinavir soft-gel capsule: an updated review of its use in the management of HIV infection.

Saquinavir is a potent and highly selective HIV protease inhibitor. Initially formulated as a hard-gel capsule (HGC), saquinavir was the first protease inhibitor available commercially for the treatment of patients with HIV infection. The limited oral bioavailability of saquinavir HGC has been improved significantly with the introduction of a soft-gel capsule (SGC) formulation. Saquinavir SGC displays greater than dose-proportional pharmacokinetics and mean area under the plasma concentration-time curve (AUC) values are 8- to 10-fold higher with saquinavir SGC 1200 mg 3 times daily than with the HGC formulation 600 mg 3 times daily, the recommended dosages of the 2 formulations. In combination with other protease inhibitors (particularly "low dose" ritonavir), the oral bioavailability of saquinavir (as either the HGC or SGC formulation) is markedly increased, allowing for reduced dosing frequency and/or dosage. The efficacy and tolerability of once- or twice-daily saquinavir SGC/"low dose" ritonavir combinations are currently being evaluated in patients with HIV infection. Data (up to 48 weeks) from noncomparative and comparative clinical trials evaluating saquinavir SGC-containing combination regimens in adult patients with HIV infection, support and strengthen the clinical efficacy profile of the drug that was demonstrated in initial trials. In antiretroviral therapy-naive and -experienced patients, saquinavir SGC combined with > or =2 nucleoside reverse transcriptase inhibitors (NRTIs), or nelfinavir, or nelfinavir plus 2 NRTIs or nonnucleoside reverse transcriptase inhibitors (NNRTIs), markedly improved immunological and virological surrogate markers (increased mean CD4+ cell counts and decreased mean plasma HIV RNA levels) of HIV infection. Saquinavir SGC demonstrated a trend to greater antiviral efficacy (measured by improvements in surrogate markers) than the HGC formulation (not statistically significant); a significantly greater proportion of patients treated with saquinavir SGC had plasma HIV RNA levels <400 copies/ml than patients receiving the HGC formulation. In the first direct comparison of 2 protease inhibitors, saquinavir SGC plus 2 NRTIs demonstrated similar antiviral efficacy to indinavir plus 2 NRTIs in patients with HIV infection (almost all of whom were antiretroviral therapy-naive); at 24 weeks, a significantly greater increase in CD4+ cell count from baseline was obtained in the saquinavir SGC group compared with the indinavir group, although this difference was not apparent at week 32. Triple therapy with saquinavir SGC plus 2 NRTIs was as effective as nelfinavir-containing triple therapy, or quadruple therapy (saquinavir SGC plus 2 NRTIs plus nelfinavir) in markedly suppressing HIV RNA levels in antiretroviral therapy-experienced or -naive patients. Saquinavir SGC is generally well tolerated. Gastrointestinal disturbances (generally nausea, diarrhoea, abdominal pain, vomiting and dyspepsia of moderate or greater intensity) are the most common adverse events associated with saquinavir SGC-containing therapy. In comparative trials, saquinavir SGC-containing therapy was as well tolerated as indinavir- and nelfinavir-containing therapy; although there were no statistical differences between treatment groups, the incidence of diarrhoea was lower in patients receiving saquinavir SGC compared with nelfinavir, saquinavir SGC plus nelfinavir (all combined with 2 NRTIs) or saquinavir SGC plus nelfinavir without additional therapy. Compared with the HGC formulation, saquinavir SGC appears to be associated with a higher overall incidence of adverse events. Clinical trial data have shown that as part of triple or quadruple combination therapy, saquinavir SGC is an effective and generally well tolerated protease inhibitor in antiretroviral therapy-naive or -experienced patients with HIV infection. (ABSTRACT TRUNCATED)

Resistance, Fitness, Adherence, and Potency

ANEAR-UNIFORMLY FATAL CLINICAL SYNDROME, ACquired immunodeficiency syndrome (AIDS), has been transformed during the past 5 years into a treatable infectious disease. The availability of potent antiretroviral agents coincided with the ability to measure levels of circulating virus in vivo. When used in tandem, an understanding of human immunodeficiency virus (HIV) replication dynamics in vivo was made possible, forming the scientific basis for the use of combination antiretroviral therapy. However, the treatment of HIV infection remains far from perfect, and new issues arise with regularity. Critical to achieving optimal therapeutic outcomes is an understanding of treatment failure. Early clinical trials of protease inhibitor monotherapy suggested that the pathway to treatment failure was exclusively via drug resistance. Viral rebound was thought to reflect failure of all components of a regimen. Furthermore, it was assumed that the absence of resistance-conferring genotypic changes reflected patient nonadherence. In this issue of THE JOURNAL, articles by Descamps and colleagues and Havlir and colleagues question these assumptions in the context of 2 large clinical trials, Trilege and AIDS Clinical Trials Group 343. The inferior outcomes observed in patients randomly assigned to receive less intensive maintenance therapy have been recently published. In the articles in this issue, the authors seek to understand the findings. In the Trilege Study, a 3-month induction phase with zidovudine, lamivudine, and indinavir was followed by randomization to either zidovudine and lamivudine, zidovudine and indinavir, or continued triple-drug therapy if the level of HIV RNA in plasma was less than 500 copies/mL. The primary end point was virologic failure, defined by 2 consecutive plasma measurements above 500 copies/mL on 2 consecutive visits, 6 weeks apart. Fifty-eight (20.8%) of the 279 randomly assigned patients met this end point, 29 receiving zidovudine and lamivudine, 21 receiving zidovudine and indinavir, and 8 receiving triple therapy. Fifty-eight study patients with durable virologic suppression were carefully selected by investigators as case-controls. The results of genotypic studies revealed the presence of the lamivudine resistance-conferring M184V substitution in reverse transcriptase in nearly all patients treated with lamivudine. However, primary-resistance mutations associated with reduced susceptibility to indinavir did not emerge during combination therapy with zidovudine and indinavir or triple therapy. Similarly, zidovudine-associated resistanceconferring mutations were rare and when present were confined to changes at codons 41 and 70 of reverse transcriptase. Adherence as measured by pill counts revealed a statistically significantdifference inmedianadherenceratesbetween cases and controls for patients prescribed either zidovudine or indinavir during maintenance therapy. Furthermore, patients randomly assigned to receive zidovudine with indinavir only demonstrated statistically significant differences in adherence rates compared with controls. Plasma indinavir levelswere found tobe lower thanexpected in2groups, those failing triple therapy and those failing zidovudine and indinavir maintenance in association with a greater loss in antiviral efficacy. Indinavir levels tended to be in the expected range in those patients in the zidovudine and indinavir group in whom virologic failure was associated with a modest loss ofantiviralactivity.Ofnote,plasmaindinavir levelswereclearly higher in controls compared with cases in both the triple therapy and zidovudine and indinavir groups. In the AIDS Clinical Trials Group 343 study, after a 6-month induction with the same triple combination regimen as used in Trilege, patients with plasma HIV RNA levels below 200 copies/mL were randomly assigned to receive zidovudine and lamivudine, indinavir monotherapy, or continued triple therapy. Patients were followed up monthly and the study end point, virologic failure, was defined as a subsequent plasma HIV RNA level of 200 copies/mL or greater. Plasma indinavir levels and resistance testing by both genotypic assay and a novel recombinant phenotypic assay were performed retrospectively in 9 of 23

Visceral abdominal-fat accumulation associated with use of indinavir

After the addition of the protease inhibitor indinavir to combination drug regimens for HIV-1 infection, some patients have experienced an increase in abdominal girth with symptoms of abdominal fullness, distension, or bloating. We aimed to find out whether this collection of symptoms was associated with changes in abdominal fat and whether such changes were associated with indinavir use. Abdominal computed tomography was used in ten HIV-1-positive patients who had such abdominal symptoms to measure total adipose tissue (TAT) and visceral adipose tissue (VAT) at the umbilicus (L4 vertebral level). The VAT:TAT ratio in the ten cases was compared with that in ten HIV-1-infected patients who had been using indinavir without abdominal symptoms for at least 6 months and ten HIV-1-infected patients who were not using indinavir. The mean VAT:TAT ratios for the three groups-non-users, symptom-free indinavir users, and symptomatic indinavir users-were 0.40 (SD 0.15), 0.59 (0.18), and 0.70 (0.20), respectively (p=0.004). The VAT:TAT ratio correlated with duration of indinavir use (r=0.47, p=0.01). The mean areas of VAT for the three groups were 106 cm2 (SD 72), 141 cm2 (65) and 202 cm2 (93), respectively (p=0.03). The mean body-mass index of the groups was similar, and patients in the two indinavir groups did not gain a significant amount of weight after starting the drug. Serum triglyceride values increased after starting indinavir and correlated with VAT:TAT ratios. Our data suggest that some HIV-1-infected patients on indinavir treatment accumulate intra-abdominal fat that may cause abdominal symptoms. Recent evidence suggests that other HIV-1 protease inhibitors may be associated with changes in body-fat distribution. Larger studies of protease-inhibitor treatment are needed to investigate this association further and to investigate metabolic or endocrine mechanisms that may underlie this phenomenon.