Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Indinavir”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1998

Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5: mechanism-based inactivation of cytochrome P4503A by ritonavir.

Both ritonavir and indinavir were readily metabolized by human intestinal microsomes. Comparison of the patterns of metabolites in incubations with enterocyte microsomes and expressed cytochrome P450 (CYP) isozymes and immunoinhibition and chemical inhibition studies showed the essential role of the CYP3A subfamily in the metabolism of both protease inhibitors by the small intestine. Ritonavir was similarly biotransformed by microsomes containing expressed CYP3A4 or CYP3A5 isozymes (KM = 0.05-0.07 microM, Vmax = 1-1.4 nmol/min/nmol CYP). In contrast, both the patterns of metabolites and the enzyme kinetic parameters for the metabolism of indinavir by expressed CYP3A5 (KM = 0.21 microM, Vmax = 0.24 nmol/min/nmol CYP) and CYP3A4 (KM = 0.04 microM, Vmax = 0.68 nmol/min/nmol CYP) were different. The biotransformation of both indinavir and ritonavir in human enterocyte microsomes was characterized by very low KM values (0.2-0.4 microM for indinavir and <0.1 microM for ritonavir). The Vmax for indinavir metabolism was greater in enterocyte (163 +/- 35 pmol/min/mg protein) than in liver (68 +/- 44 pmol/min/mg protein) microsomes. The metabolism of ritonavir in liver and enterocyte microsomes was associated with inactivation of CYP3A. The initial Vmax for ritonavir metabolism by enterocyte microsomes was 89 +/- 59 pmol/min/mg protein. The apparent inactivation rate constants for intestinal CYP3A and expressed CYP3A4 were 0.078 and 0.135 min-1, respectively. Metabolic inactivation of CYP3A by ritonavir explains the improved bioavailability and pharmacokinetics of ritonavir and the sustained elevation of blood levels of other, concomitantly administered, substrates of CYP3A.

Anti-HIV Agents↗
PubMed1998

Indinavir crystalluria: identification of patients at increased risk of developing nephrotoxicity.

OBJECTIVE: To determine whether the protease inhibitor indinavir sulfate, which is extremely insoluble at physiologic pH levels and which is known to be associated with nephrolithiasis, is associated with crystalluria at a usual therapeutic dose. METHODS: Freshly voided urine from 27 male human immunodeficiency virus patients being treated with indinavir at a dose of 800 mg, tid, in an outpatient setting and from 20 healthy subjects undergoing routine physical examination was subjected to dipstick urinalysis and microscopic examination of urinary sediments. RESULTS: Three (11%) of 27 patients treated with indinavir developed highly characteristic crystalluria during the course of therapy. No such crystals were observed in the urine of the 20 healthy subjects. CONCLUSION: Indinavir crystalluria was identified in asymptomatic patients treated with usual therapeutic doses of the drug. Screening urines of patients taking indinavir may be useful in identifying patients at risk for developing nephrotoxicity.

Crystallization↗
PubMed1998

Simultaneous vs sequential initiation of therapy with indinavir, zidovudine, and lamivudine for HIV-1 infection: 100-week follow-up.

CONTEXT: Combination antiretroviral therapy can markedly suppress human immunodeficiency virus (HIV) replication but the duration of HIV suppression varies among patients. OBJECTIVE: To compare the antiretroviral effect of a 3-drug regimen started simultaneously or sequentially in patients with HIV infection. DESIGN: A multicenter, randomized, double-blind study, modified after at least 24 weeks of blinded therapy to provide open-label 3-drug therapy with follow-up through 100 weeks. SETTING: Four clinical research units PATIENTS: Ninety-seven patients with HIV infection who had taken zidovudine for at least 6 months with serum HIV RNA level of at least 20000 copies/mL and CD4 cell count of 0.05 to 0.40 x 10(9)/L. INTERVENTIONS: Patients were initially randomized to receive 1 of 3 antiretroviral regimens: indinavir, 800 mg every 8 hours; zidovudine, 200 mg every 8 hours and lamivudine, 150 mg every 12 hours; or all 3 drugs. After at least 24 weeks of blinded therapy, all patients received open-label 3-drug therapy. MAIN OUTCOME MEASURES: Antiretroviral activity was assessed by changes in HIV RNA level and CD4 cell count from baseline. Data through 100 weeks were summarized. RESULTS: Simultaneous initiation of indinavir, zidovudine, and lamivudine suppressed HIV RNA in 78% (25/32) of contributing patients to less than 500 copies/mL and increased CD4 cell count to a median of 0.209 x 10(9)/L above baseline at 100 weeks. When these 3 drugs were initiated sequentially, only 30% to 45% of contributing patients (10 of 33 in the zidovudine-lamivudine group and 13 of 29 in the indinavir group, respectively) had a sustained reduction in HIV RNA to less than 500 copies/mL, and median CD4 cell count increased to 0.101 to 0.163 x 10(9)/L above baseline at 100 weeks. CONCLUSIONS: A 3-drug combination of indinavir, zidovudine, and lamivudine started simultaneously has durable antiretroviral activity for at least 2 years. Sequential initiation of the same 3 drugs is much less effective.

Anti-HIV Agents↗
PubMed2005

Indinavir impairs endothelial function in healthy HIV-negative men.

BACKGROUND: Potent antiretroviral treatment has drastically reduced mortality in HIV-infected patients but may accelerate atherosclerotic disease, which could be partially mediated via endothelial dysfunction. METHODS: In 8 HIV-negative healthy males, leg blood flow responses to intraartery infusions of methacholine chloride (Mch), sodium nitroprusside, and NG-mono-methyl-L-arginine (L-NMMA) were measured before and after 4 weeks of daily oral indinavir. In the same subjects, we also assessed the effect of indinavir on lipids, insulin sensitivity, markers of inflammation, as well as oxidative stress. RESULTS: After 4 weeks of indinavir, the endothelium-dependent response to methacholine chloride was impaired (195% +/- 38% vs 83% +/- 13%, P < .05), the response to NG-mono-methyl-L-arginine (nitric oxide-dependent tone) was nearly abrogated (-30% +/- 4% vs -1% +/- 11%, P < .05), whereas the endothelium-independent response to sodium nitroprusside remained unchanged. Fasting insulin levels increased from 5.8 +/- 1.2 to 7.0 +/- 1.4 microU/mL (P < .05), and HOMA-IR scores increased from 1.3 +/- 0.3 to 1.6 +/- 0.3 U (P < .05). There were no changes in blood pressure, lipids, markers of inflammation, or oxidative stress. CONCLUSIONS: Four weeks of the HIV-1 protease inhibitor indinavir, in the absence of HIV-1 infection, causes vascular dysfunction most likely at the level of endothelial nitric oxide production. The vascular dysfunction may be mediated partially by the concomitant induction of insulin resistance but other mechanisms cannot be ruled out.

Adult↗
PubMed2005

Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers.

BACKGROUND: Hypertension is an important modifiable cardiac risk factor in human immunodeficiency virus (HIV)-infected patients. Calcium channel blockers are substrates of cytochrome P450 3A and are commonly prescribed for hypertension. We evaluated potential bidirectional pharmacokinetic interactions between calcium channel blockers and coadministered indinavir and ritonavir. METHODS: Healthy HIV- seronegative subjects received 120 mg diltiazem daily or 5 mg amlodipine daily for days 1 to 7 and 20 to 26. All subjects received 100 mg ritonavir and 800 mg indinavir every 12 hours on days 8 to 26. Twenty-four-hour pharmacokinetic collection was performed on days 7 and 26, with 12-hour collection on day 19. RESULTS: Indinavir plus ritonavir increased the median amlodipine area under the curve from 0 to 24 hours (AUC) by 89.8%, from 122 to 230 ng.h/mL (n = 18, P < .0001), and increased the median diltiazem AUC by 26.5%, from 800 to 1060 ng.h/mL (n = 13, P = .06). Of 13 subjects, 2 (15%) had greater than 4-fold increases in diltiazem AUC. Desacetyldiltiazem AUC increased by 102.2% (P = .001), and desmethyldiltiazem AUC decreased by 27.4% (P = .01). Neither amlodipine nor diltiazem affected steady-state AUCs of the protease inhibitors. No serious cardiovascular adverse effects were observed. CONCLUSIONS: Indinavir plus ritonavir increases the AUCs of both amlodipine and diltiazem, which may result in an increased response. If coadministration is indicated, amlodipine or diltiazem should be initiated at low doses with careful titration to response and side effects.

Adolescent↗
PubMed2004

The ICH guidance in practice: stress degradation studies on indinavir sulphate and development of a validated specific stability-indicating HPTLC assay method.

A sensitive, selective, precise and stability-indicating high-performance thin layer chromatography (HPTLC) method for analysis of indinavir sulphate both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of carbon tetrachloride/chloroform/methanol/10% v/v ammonia (4:4.5:1.5:0.05, v/v/v/v). Densitometric analysis of indinavir sulphate was carried out in the absorbance mode at 260 nm. This system was found to give compact spots for indinavir sulphate (Rf value of 0.43 +/- 0.02, for six replicates). Indinavir sulphate was subjected to acid and alkali hydrolysis, oxidation, dry and wet heat treatment, and photo degradation. The drug undergoes degradation under acidic and basic conditions, oxidation, dry and wet heat treatment, and photo degradation. Also the degraded products were well resolved from the pure drug with significantly different Rf values. The method was validated for linearity, precision, robustness, limit of detection (LOD), limit of quantitation (LOQ), specificity and accuracy. Linearity was found to be in the range of 100-6000 ng/spot with significantly high value of correlation coefficient r2 = 0.997 +/- 0.64. The linear regression analysis data for the calibration plots showed good linear relationship with r2 = 0.999 +/- 0.002 in the working concentration range of 1000-6000 ng/spot. The LOD and LOQ were 40 and 120 ng/spot, respectively. Statistical analysis proves that the method is repeatable and specific for the estimation of the said drug. As the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one. Moreover, the proposed HPTLC method was utilized to investigate the kinetics of acid degradation process. Arrhenius plot was constructed and activation energy was calculated.

Chromatography, High Pressure Liquid↗
PubMed2004

Efficacy of two modalities of triple HIV therapy: probable superiority of indinavir.

The introduction of the so-called highly active antiretroviral therapies has had an impact on the natural history of the HIV infection. The aim of this contribution is to assess the differences in terms of plasma viral load (VL), as a reflection of therapy success or failure. A retrospective study was made of the changes in VL in two cohorts of patients depending on the drugs included in the triple therapy prescribed to them. The comparison of the triple therapies containing any reverse transcriptase inhibitor and different protease inhibitors, indinavir (IDV) (239 patients) versus saquinavir (SQV) or ritonavir (RTV) (138 subjects), showed a significantly higher percentage of patients reaching a 'non-detectable' VL among those receiving indinavir (67.8% versus 54.3%; P = 0.011). The interval before VL levels rose above 30,000 RNA copies/ml was different in the two groups: 385 days (276-495 days) for therapies including indinavir, and 239 days (86-391 days) for saquinavir or ritonavir. This seems to support the excellent behaviour of indinavir when its efficiency is compared with other protease inhibitors acting as potential competitors.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Reversed-phase liquid chromatography with ultraviolet detection for simultaneous quantitation of indinavir and propranolol from ex-vivo rat intestinal permeability studies.

A simple, rapid, sensitive and specific reversed-phase high performance liquid chromatographic (RP-HPLC) method involving ultraviolet detection (lambda = 210 nm) was developed for analysis of indinavir along with propranolol in samples obtained from ex vivo intestinal permeability studies. Chromatography was carried out on C-18 column with mobile phase comprising of phosphate buffer-acetonitrile (68:32, v/v) pumped at flow rate of 1 ml/min. The proposed method has a short run time of 12 min and involves a simple sample preparation for the purpose of reducing permeability model artifacts and to concentrate the samples. Fluorescein was used as internal standard. The proposed method has been validated with regard to specificity, detection limit, recovery, accuracy and precision. For both the drugs, method was found to be selective, linear (R(2) approximately 0.999), accurate (recovery = 100-105%) and precise (<3% R.S.D.) in the range of 2-20 microg/ml. The limit-of-detection and limit-of-quantification of the method were 40 ng/ml and 100 ng/ml for indinavir, and 30 and 80 ng/ml for propranolol, respectively. Indinavir, a widely prescribed HIV protease inhibitor, suffer from bioavailability problems where involvement of P-glycoprotein mediated drug efflux may play a significant role. The proposed method was successfully applied for intestinal permeability of indinavir to estimate the contribution of P-glycoprotein in limiting its oral bioavailability. The advantage of the developed method lies in the simultaneous determination of propranolol, a passive integrity marker, routinely employed in permeability studies and its selectivity in presence of various P-gp modulators and permeability markers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Synthesis and anti-HIV activity of glucose-containing prodrugs derived from saquinavir, indinavir and nelfinavir.

With the aim at improving the transport of the current HIV protease inhibitors across the intestinal and blood brain barriers and their penetration into the central nervous system, the synthesis of various acyl and carbamatoyl glucose-containing prodrugs derived from saquinavir, indinavir and nelfinavir, their in vitro stability with respect to hydrolysis, and their anti-HIV activity have been investigated. D-Glucose, which is actively transported across these barriers, was connected through its 3-hydroxyl to these antiproteases via a linker. The liberation of the active free drug during the incubation time of the prodrugs with the cells was found to be crucial for HIV inhibition. The labile ester linking of the glucose-containing moiety to the peptidomimetic hydroxyl of saquinavir or to the indinavir C-8 hydroxyl, which is not part of the transition state isostere, is not an obstacle for anti-HIV activity. This is not the case for its stable carbamate linking to the peptidomimetic hydroxyl of saquinavir, indinavir and nelfinavir. The chemical stability with respect to hydrolysis of some of the saquinavir and indinavir prodrugs reported here, the liberation rate of the active free drug and the HIV inhibitory potency are acceptable for an in vivo use of these prodrugs. These glucose-linked ester and carbamate prodrugs display a promising therapeutic potential provided that their bioavailability, penetration into the HIV sanctuaries, and/or the liberation of the active free drug from the carbamate prodrugs are improved. Furthermore, no cytotoxicity was detected for the prodrugs for concentrations as high as 10 or even 100 microM, thus indicating an encouraging therapeutic index.

Carbamates↗
PubMed2001

[Paronychia in patients infected with HIV treated with indinavir].

A retrospective study of cases of paronychia associated with anti-retroviral therapy diagnosed in two general hospitals is here reported. Lesions appeared from 3 and 48 months after institution of therapy. At diagnosis, 84.6% of patients were on indinavir therapy. CD4 values ranged from 120 and 1,332 cells/mm3 and viral load was lower than 200 copies/ml in 92.3 of cases. Conservative therapy was applied in 7 patients and surgery in 6. In all patients indinavir therapy was discontinued, and cure was achieved 16 weeks later. The "retinoid" effect of indinavir is discussed as likely pathogenic explanation for this complications. We advocate for topic therapy and change of anti-retroviral therapy, reserving surgery for patients not responding to therapy. Pain and functional limitation caused by this non uncommon complication (1.6% of our patients treated with anti-retroviral agents) makes its knowledge necessary and an active search by clinicians in patients receiving indinavir therapy.

Adult↗
PubMed1997

Urolithiasis associated with the protease inhibitor indinavir.

OBJECTIVES: To report the association between the protease inhibitor indinavir and the development of urolithiasis. METHODS: Case reports of three adult patients infected with the human immunodeficiency virus who developed surgical renal stones while being treated with indinavir are presented. RESULTS: Of the 3 patients requiring surgical intervention, stone analyses were available in 2. One stone revealed an inner core of an unidentifiable crystal surrounded by calcium oxalate, and another was found to have indinavir components as determined by thin-layer chromatography and gas chromatography-mass spectrometry. Metabolic evaluation of all 3 patients identified significant hypocitraturia as an isolated finding. CONCLUSIONS: The widely used protease inhibitor indinavir is associated with the development of urolithiasis and may act as a nidus for heterogeneous nucleation leading to the development of mixed urinary stones. Surgical intervention may be necessary in some cases. Underlying metabolic abnormalities may contribute to the increased incidence of stone formation. Urologists and other health care providers should be aware of this association, as combined medical and surgical intervention may be necessary.

Adult↗
PubMed2000

Acute tubulointerstitial nephritis attributable to indinavir therapy.

Indinavir sulfate has been reported to cause asymptomatic crystalluria and nephrolithiasis in patients with human immunodeficiency virus (HIV) infection. Patients taking indinavir may present with asymptomatic crystalluria, nephrolithiasis with frank renal colic and obstruction, flank pain in the absence of nephrolithiasis, and dysuria or urgency. Asymptomatic crystalluria has been described as benign. Discontinuation of the drug has not been recommended in the absence of nephrolithiasis. We report two HIV-positive patients receiving indinavir who developed acute interstitial nephritis with foreign body giant cell reaction on renal biopsies. Both patients had asymptomatic crystalluria, although crystals were associated with clumps of white blood cells (WBCs) on urinalysis in one patient. Both cases show that the inflammatory response was significant enough to lead to tubular injury and acute renal impairment. Our findings suggest that asymptomatic crystalluria attributable to indinavir may illicit an inflammatory response with acute renal insufficiency, warranting monitoring of renal function, especially in patients with crystalluria.

Adult↗
PubMed1999

Determination of indinavir, potassium sorbate, methylparaben, and propylparaben in aqueous pediatric suspensions.

A gradient, reversed phase, HPLC method was developed for simultaneous analysis of potassium sorbate, methylparaben, propylparaben, and indinavir in aqueous suspensions that contain a proprietary orange flavoring and Magnasweet sweetener enhancer (MacSanrews and Forbes Company, Magnasweet product brochure). The chromatographic separation is performed on an Eclipse XDB-C8 column using a gradient run with an analysis time of 35 min. The mobile phase consists of acetonitrile and acetonitrile:citrate buffer, pH 4.0 (20:80 v/v). The method successfully separates the three preservatives, indinavir (active ingredient), the orange flavoring, the Magnasweet species, and the indinavir lactone degradate. Recovery, linearity, and precision results for the three preservatives and indinavir are described. The method applies to two types of formulations: Xanthan Gum suspension and NanoSystems suspension.

Anti-HIV Agents↗
PubMed2003

Analysis of the protease sequences of HIV-1 infected individuals after Indinavir monotherapy.

BACKGROUND: Protease inhibitors (PI) are an important HIV-1 treatment tool. The HIV-1 genetic diversity as a result of antiretroviral exposure is a potential barrier to successful antiretroviral therapy. OBJECTIVES: To describe the impact of the selective pressure of the PI Indinavir in the protease region of the pol gene of HIV-1. STUDY DESIGN: We have examined the extent of protease sequence heterogeneity in previously antiretroviral drug naive HIV-1 infected individuals receiving Indinavir as monotherapy for at least 48 weeks. RESULTS: Analysis based on the consensus of this group of sequences showed regions with higher and lower polymorphism. The degree of genetic variation was greater in regions less critical for the structure and function of the enzyme. To investigate the selective pressure imposed by drug therapy, we have analyzed the rate of synonymous (ds) and nonsynonymous (dn) substitutions. The three critical regions for enzyme activity showed ds/dn ratio >1. whereas other regions had ds/dn ratio <1. The detected amino acid mutations had a trend to be conservative, thus maintaining the physical chemical amino acid characteristics. Phylogenetic analysis established the presence of subtype B (n=38), subtype F (n=9), and B/F recombinants within the protease region of pol gene (n=3). More prevalent detected mutations, thought to contribute to antiretroviral resistance, were L63P (42%), L10I (35%), M36I (30%), V82A/T/F (26%). CONCLUSIONS: A great deal of predicted cross-resistance between PIs was observed. Out of the 50 individuals, 34% were considered to have major mutations to Indinavir, and 66% had minor or no mutations to Indinavir. Viral loads were significantly higher among patients with major mutations, compared with patients minor/no mutations, although no differences in the CD4 counts were found. The viral load at baseline and nadir (week 4) was able to predict the group of individuals with greater chances of selecting drug resistance related mutations.

DNA, Viral↗
PubMed2002

Simultaneous determination of indinavir, ritonavir and lopinavir (ABT 378) in human plasma by high-performance liquid chromatography.

An isocratic reversed-phase high-performance liquid chromatographic method with ultraviolet detection at 205 nm has been validated for the determination of indinavir, ritonavir and lopinavir (ABT 378) in human plasma. The ritonavir analogue A-86093.0 was used as internal standard. Good chromatographic separation was achieved using a stainless steel column packed with 5 microm Phenomenex phenyl hexyl material operated at 40 degrees C, and a mobile phase consisting of acetonitrile-10 mM potassium phosphate buffer (50:50, v/v). The calibration curve for indinavir was linear over the range of 50 to 1000 microg/l while the ritonavir and lopinavir calibration curves were linear over the range of 100 to 15,000 microg/l. The lower limit of quantitations for indinavir, ritonavir and lopinavir were 50, 100 and 100 microg/l, respectively, using 500 microl of human plasma. The validation data showed that the assay is sensitive, specific and reproducible for determination of indinavir, ritonavir and lopinavir. This method is being used in a therapeutic drug monitoring service to quantitate these therapeutic agents in patients infected with human immunodeficiency virus.

Chromatography, High Pressure Liquid↗
PubMed2004

Involvement of P-glycoprotein in the transport of saquinavir and indinavir in rat brain microvessel endothelial and microglia cell lines.

PURPOSE: Membrane-bound efflux transporters, such as P-glycoprotein (P-gp), may limit the brain entry and distribution of HIV-1 protease inhibitors and be in part responsible for HIV-1-associated dementia treatment failure. The purpose of this study was to characterize the transport properties of saquinavir and indinavir in a brain microvessel endothelial cell line and in microglia, the immune cells of the brain and primary HIV-1 cellular target. METHODS: Biochemical and transport studies were performed in an immortalized rat brain endothelial cell line (RBE4), a rat microglia cell line (MLS-9), and a P-gp overexpressing Chinese hamster ovary cell line (CHRC5). RESULTS: Western blot analysis using the P-gp monoclonal antibody C219 detected a single band at approximately 170 to 180 kDa (a size previously reported for P-gp) in all cell lines. Cellular accumulation of [14C]saquinavir and [3H]indinavir by RBE4, MLS-9, and CHRC5 monolayers was significantly enhanced in the presence of P-gp inhibitors, HIV-1 protease inhibitors, the ATPase inhibitor sodium azide, and the ATP depleting agent 2',4'-dinitrophenol respectively. [14C]Saquinavir and [3H]indinavir efflux from both cell systems was rapid and significantly reduced in the presence of PSC833. CONCLUSIONS: These results provide evidence for P-gp mediated transport of saquinavir and indinavir in RBE4 and MLS-9 and suggest that this transporter can restrict, at least in part, the permeation of HIV-1 protease inhibitors at both the brain barrier site and in brain parenchyma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team.

BACKGROUND: The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine. METHODS: A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count (50 or fewer vs. 51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily regimens: 600 mg of zidovudine (or stavudine) and 300 mg of lamivudine, or that regimen with 2400 mg of indinavir. The primary end point was the time to the development of the acquired immunodeficiency syndrome (AIDS) or death. RESULTS: The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine, and lamivudine (6 percent) than with zidovudine and lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence interval, 0.33 to 0.76; P=0.001). Mortality in the two groups was 1.4 percent and 3.1 percent, respectively (estimated hazard ratio, 0.43; 95 percent confidence interval, 0.19 to 0.99; P=0.04). The effects of treatment were similar in both CD4 cell strata. The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results. CONCLUSIONS: Treatment with indinavir, zidovudine, and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy.

BACKGROUND: The new protease inhibitors are potent inhibitors of the human immunodeficiency virus (HIV), and in combination with other antiretroviral drugs they may be able to cause profound and sustained suppression of HIV replication. METHODS: In this double-blind study, 97 HIV-infected patients who had received zidovudine treatment for at least 6 months and had 50 to 400 CD4 cells per cubic millimeter and at least 20,000 copies of HIV RNA per milliliter were randomly assigned to one of three treatments for up to 52 weeks: 800 mg of indinavir every eight hours; 200 mg of zidovudine every eight hours combined with 150 mg of lamivudine twice daily; or all three drugs. The patients were followed to monitor the occurrence of adverse events and changes in viral load and CD4 cell counts. RESULTS: The decrease in HIV RNA over the first 24 weeks was greater in the three-drug group than in the other groups (P<0.001 for each comparison). RNA levels decreased to less than 500 copies per milliliter at week 24 in 28 of 31 patients in the three-drug group (90 percent), 12 of 28 patients in the indinavir group (43 percent), and none of 30 patients in the zidovudine-lamivudine group. The increase in CD4 cell counts over the first 24 weeks was greater in the two groups receiving indinavir than in the zidovudine-lamivudine group (P< or =0.01 for each comparison). The changes in the viral load and the CD4 cell count persisted for up to 52 weeks. All the regimens were generally well tolerated. CONCLUSIONS: In most HIV-infected patients with prior antiretroviral therapy, the combination of indinavir, zidovudine, and lamivudine reduces levels of HIV RNA to less than 500 copies per milliliter for as long as one year.

Adult↗