ritonavir and AIDS-Related-Opportunistic-Infections

Complete delineation of the HIV-1 life cycle has resulted in the development of several antiretroviral drugs. Twenty-five therapeutic agents belonging to five different classes are currently available for the treatment of HIV-1 infections. Advent of triple combination antiretroviral therapy has significantly lowered the mortality rate in HIV patients. However, fungal infections still represent major opportunistic diseases in immunocompromised patients worldwide.. Antiretroviral drugs that target enzymes and/or proteins indispensable for viral replication are discussed in this article. Fungal infections, causative organisms, epidemiology and preferred treatment modalities are also outlined. Finally, observed/predicted drug-drug interactions between antiretrovirals and antifungals are summarized along with clinical recommendations.. Concomitant use of amphotericin B and tenofovir must be closely monitored for renal functioning. Due to relatively weak interactive potential with the CYP450 system, fluconazole is the preferred antifungal drug. High itraconazole doses (> 200 mg/day) are not advised in patients receiving booster protease inhibitor (PI) regimen. Posaconazole is contraindicated in combination with either efavirenz or fosamprenavir. Moreover, voriconazole is contraindicated with high-dose ritonavir-boosted PI. Echinocandins may aid in overcoming the limitations of existing antifungal therapy. An increasing number of documented or predicted drug-drug interactions and therapeutic drug monitoring may aid in the management of HIV-associated opportunistic fungal infections.

Topics: AIDS-Related Opportunistic Infections; Alkynes; Anti-Retroviral Agents; Antifungal Agents; Benzoxazines; Carbamates; Cyclopropanes; Drug Interactions; Drug Monitoring; Echinocandins; Furans; HIV Infections; HIV Protease Inhibitors; Humans; Itraconazole; Mycoses; Organophosphates; Pyrimidines; Ritonavir; Sulfonamides; Triazoles; Voriconazole

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Aryl Hydrocarbon Hydroxylases; Bundle-Branch Block; Cytochrome P-450 CYP3A; Drug Interactions; Enzyme Inhibitors; Heart; Heart Block; HIV Protease Inhibitors; Humans; Lamivudine; Lopinavir; Male; Middle Aged; Oxidoreductases, N-Demethylating; Pyrimidinones; Reverse Transcriptase Inhibitors; Ritonavir; Syncope; Zidovudine

The current study was conducted to determine if efavirenz (EFV) or atazanavir/ritonavir (ATV/r)-based combination antiretroviral therapy (cART) impacted steady-state atovaquone plasma concentrations in human immunodeficiency virus (HIV)-infected patients receiving treatment doses of atovaquone.. Thirty HIV-infected volunteers were recruited, 10 taking no cART and 10 each taking cART that included EFV or ATV/r. Subjects were randomly assigned to atovaquone 750 mg twice daily (BID) for 14 days followed by atovaquone 1500 mg BID for 14 days, or vice-versa, with a washout period in between. On day 14 of each phase, blood was sampled for pharmacokinetic studies, and the area under the concentration-time curve (AUCτ) and average concentration (C avg) were calculated and compared using an unpaired t test.. Twenty-nine subjects completed both dosing cohorts. Subjects receiving EFV-based cART had 47% and 44% lower atovaquone AUCτ than subjects not receiving cART at atovaquone doses of 750 mg BID and 1500 mg BID, respectively (P≤ .01). Only 5 of 10 subjects receiving EFV-based cART plus atovaquone 750 mg BID had an atovaquone C avg>15 µg/mL, which has previously been associated with successful treatment of Pneumocystis jirovecipneumonia. AUCτ and Cavg did not significantly differ for concurrent ATV/r for 750 mg BID or 1500 mg BID when compared to the group not receiving cART. Nine of 10 subjects not receiving cART, 8 of 10 subjects receiving ATV/r, and 2 of 10 subjects receiving EFV in combination with atovaquone 750 mg BID achieved an atovaquone C avg>18.5 µg/mL, a concentration that has previously been associated with successful treatment of Toxoplasmaencephalitis (TE).. These data suggest that the currently recommended dose of atovaquone 750 mg BID for treatment of mild to moderate PCP may not be adequate in patients receiving concurrent EFV. Furthermore, doses lower than the currently recommended dose of 1500 mg BID may achieve plasma concentrations adequate to treat TE in HIV-infected patients not receiving EFV.. NCT01479361.

Topics: Administration, Oral; Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Anti-Infective Agents; Atazanavir Sulfate; Atovaquone; Benzoxazines; Cyclopropanes; Drug Interactions; Drug Therapy, Combination; Encephalitis; Female; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Reverse Transcriptase Inhibitors; Ritonavir; Toxoplasmosis, Cerebral; Young Adult

To assess the drug concentrations, efficacy and safety of concomitant use of rifampicin and regimens containing ritonavir/saquinavir (400mg/400mg twice daily) in tuberculosis-HIV treatment-naive patients.. This was an open-label, non-randomised, multiple-dose study. On study day (D)1, tuberculosis treatment (rifampicin 600mg/isoniazid 400mg per day fasting plus pyrazinamide 2 g/day) was introduced in 30 patients. On D31, highly active antiretroviral therapy (HAART) consisting of two nucleoside analogues plus ritonavir/saquinavir 400mg/400mg twice daily was initiated (n = 20). The pharmacokinetics were assayed with a validated reversed-phase HPLC method before the introduction of HAART on D30 (for rifampicin), after 30 days of HAART at D60 (for rifampicin plus ritonavir/saquinavir), and at the end of the study (without rifampicin) on D210 (for ritonavir/saquinavir). Clinical evaluations were performed on a monthly basis. CD4 counts and viral load were collected on D30, D60 and D180. Genotyping test for HIV was collected at baseline and at D180. Primary endpoints were drug concentration and viral load at D180 (<80 copies/mL). Secondary endpoints were presence of grade 3 and serious adverse events, clinical improvement, CD4 count and genotypic resistance to ritonavir/saquinavir.. Ten patients dropped out of the study during tuberculosis therapy alone. Mean (+/- SD) baseline CD4 count (on D30) was 151.89 (+/- 146.77) cells/mm(3) and viral load was 5.34 (+/- 0.4) log. During the antiretroviral therapy, 15 patients dropped out, 14 because of adverse events. One patient (of five) presented a viral load of <80 copies/mL at D180. All but one patient increased CD4 counts from baseline. No genotypic resistance was detected. Clinical improvement was evident in all five patients who tolerated the therapy. Serum concentrations of ritonavir/saquinavir and rifampicin remained within the therapeutic range.. Therapeutic concentrations of the studied drugs and reduction of viral load were achieved; adverse events are the main limitation of use of a ritonavir/saquinavir regimen in treatment-naive patients, but its clinical benefits were evident.

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Antiretroviral Therapy, Highly Active; Area Under Curve; Bisexuality; CD4 Lymphocyte Count; Drug Administration Schedule; Female; Half-Life; HIV Infections; HIV Protease Inhibitors; Homosexuality; Humans; Karnofsky Performance Status; Male; Metabolic Clearance Rate; Rifampin; Ritonavir; Saquinavir; Time Factors; Treatment Outcome; Tuberculosis; Viral Load

Topics: AIDS-Related Opportunistic Infections; Drug Therapy, Combination; Hepatitis B, Chronic; Hepatitis C, Chronic; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Reverse Transcriptase Inhibitors; Ritonavir

Our primary aim was to evaluate the plasma exposures and safety of rifabutin and its active 25-O-desacetyl metabolite during concomitant therapy of intermittent rifabutin dosing regimens with a combination of ritonavir and saquinavir.. Twenty-four patients without mycobacterial infection who were human immunodeficiency virus seropositive and who were receiving 400 mg each of ritonavir and saquinavir twice daily participated in a 3-period, 2-group longitudinal pharmacokinetic study. Patients were equally randomized to receive 300 mg of rifabutin every 7 days (group 1) or 150 mg of rifabutin every 3 days (group 2) for 8 weeks. Blood samples were collected over the dosing intervals of the protease inhibitors at baseline (period 1) and of the 3 drugs after 4 weeks (period 2) and 8 weeks (period 3) for HPLC measurement of plasma concentrations of the 3 drugs and 25-O-desacetylrifabutin.. Nineteen patients (group 1, n = 10; group 2, n = 9) completed the study. Five individuals withdrew from the study; 3 of them experienced side effects, and 2 were lost to follow-up. For combined groups, mean saquinavir and ritonavir overall (area under the concentration-time curve [AUC]) and peak (C(max)) plasma exposures averaged over periods 2 and 3 did not change significantly (8% to 19%; P > .05) compared with those in period 1 (90% confidence intervals, -7% to 26% for ritonavir and -2% to 38% for saquinavir). Rifabutin and metabolite AUC and C(max) exposures were stable over the 8 weeks, with intraindividual coefficients of variation of 12% to 19%. Oral clearance of rifabutin was similar in both groups (321 mL/min in group 2 versus 372 mL/min in group 1; P = .34). Rifabutin C(max) values were significantly lower in group 2 (310 ng/mL versus 496 ng/mL in group 1; P = .004). Rifabutin and metabolite predose levels were significantly higher in group 2 (rifabutin: 54 ng/mL versus 17 ng/mL; desacetyl rifabutin: 55 ng/mL versus 28 ng/mL; P < .002).. Rifabutin exposures were similar at 4 and 8 weeks and had minimal effect on ritonavir and saquinavir exposures. Intermittent rifabutin dosing over 8 weeks provided a safe and manageable regimen for concurrent therapy with a combination of ritonavir and saquinavir.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Antibiotics, Antitubercular; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Protease Inhibitors; Humans; Male; Mycobacterium Infections; Rifabutin; Ritonavir; Saquinavir

To ascertain if immunization results in the restoration of responses to recall antigens, in the development of responses to presumed neoantigens, and to identify the virologic and immunologic correlates of these responses in persons with HIV-1 infection.. Open-label study carried out at three university-affiliated AIDS Clinical Trials Units in the United States.. Thirty-one subjects participating in AIDS Clinical Trials Group Protocol 375 who had received zidovudine, lamivudine, and ritonavir for at least 48 weeks. Subjects were immunized with tetanus toxoid (TT) at entry and with inactivated hepatitis A vaccine (hep A) and keyhole limpet hemocyanin (KLH) at entry and 6 weeks. The development of antibody, lymphocyte proliferative assay (LPA), and delayed-type hypersensitivity (DTH) responses after immunization were monitored.. The LPA and DTH responses to TT improved in 57 and 68% of participants, respectively; 73 and 65% developed enhanced LPA and DTH responses to KLH. Forty-eight percent of patients developed a four-fold increase in antibody concentration to tetanus. Seventy-three percent of patients without detectable hepatitis A antibodies at baseline developed antibodies after immunization. Eighty-three percent of patients experienced at least a four-fold rise in KLH antibody concentration. Immune activation and viral load predicted poor recall responses and the number of memory CD4+ T-cells predicted good responses to recall antigens. Naïve CD4+ T-cell numbers, decrease in viral load, increases in CD4+ and CD28+ cells, and decreases in immune activation were associated with responses to presumed neoantigens.. Most HIV-infected patients treated with potent combination antiretrovirals develop responses to recall and presumed neoantigens after immunization. Functional immune restoration in response to immunization is related to control of viral replication, decreased immune activation as well as to both quantitative and qualitative restoration of circulating T- lymphocyte subpopulations.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Drug Therapy, Combination; Female; Hemocyanins; Hepatitis A Vaccines; HIV-1; Humans; Hypersensitivity, Delayed; Injections, Intradermal; Lamivudine; Male; Middle Aged; Ritonavir; T-Lymphocytes; Tetanus Toxoid; Thymus Gland; Vaccination; Viral Hepatitis Vaccines; Zidovudine

To investigate the pharmacokinetics of liposomal daunorubicin (DaunoXome) administered alone or in combination with antiviral therapy including protease inhibitors (PI) to HIV-positive patients affected by Kaposi's sarcoma (KS).. A group of 18 patients with extensive or rapidly progressing AIDS-related KS received DaunoXome at a dose of 40 mg/m2 alone or in association with a triple combination therapy consisting of one PI plus two nucleoside reverse transcriptase inhibitors (NRTI). Daunorubicin pharmacokinetics were determined in a total of 23 cycles, 6 with DaunoXome alone, 9 in combination with indinavir, 6 with ritonavir and 2 with saquinavir. Plasma samples were obtained at different times during the 72 h after DaunoXome administration. Daunorubicin and daunorubicinol plasma levels were determined by high-performance liquid chromatography.. After the DaunoXome infusion, daunorubicin was rapidly cleared from the body following, in most cases, a one-compartment open kinetic model. The daunorubicin peak concentrations, clearances and elimination half-lives were (means +/- SD): 16.3 +/- 2.8 microg/ml, 0.3 +/- 0.1 l/h per m2 and 5.6 +/- 2.6 h after DaunoXome alone; 15.1 +/- 4.9 microg/ml, 0.5 +/- 0.3 l/ h per m2 and 5.8 +/- 2.1 h after the combination with indinavir; and 14.5 +/- 2.8 microg/ml, 0.4 +/- 0.2 l/h per m2 and 6.5 +/- 3.9 h after the combination with ritonavir. In all groups, daunorubicinol plasma levels were approximately 25-30 times lower than those of the parent drug.. Our data show that there are no significant differences in the pharmacokinetic parameters of daunorubicin in patients receiving DaunoXome in combination with indinavir and ritonavir compared with those in patients not receiving PIs. Therefore in patients affected by AIDS-related KS treated with Highly Active AntiRetroviral Therapy (HAART) there is no pharmacokinetic justification for reducing the doses of DaunoXome.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antibiotics, Antineoplastic; Daunorubicin; Drug Interactions; Drug Therapy, Combination; Female; HIV Protease Inhibitors; Humans; Indinavir; Liposomes; Male; Middle Aged; Ritonavir; Saquinavir; Sarcoma, Kaposi

We prospectively studied the incidence of cytomegalovirus (CMV) retinitis in 93 patients treated with highly active antiretroviral therapy (HAART) containing a protease inhibitor (PI), during a median follow-up period of 24 months. The median initial CD4+ count was 22 cells/microl (range, 1-311 cells/microl), and the median plasma HIV viral load was 5.1 log10 copies/ml (range, 2.4-6.4 log10 copies/ml). The fundus was examined monthly in patients with a history of CMV retinitis or an initial CD4+ count <50 cells/microl and every 3 months in the other patients. Of patients with previously controlled CMV retinitis, 1 of 7 relapsed. In addition, 6 of 59 patients with a CD4+ count <50 cells/microl and no history of CMV retinitis before starting PI therapy developed CMV retinitis. Of them, 3 had at least one relapse during follow-up. CD4+ counts were <40 cells/microl at the time of primary or recurrent CMV retinitis, except in two cases (147 cells/microl and 203 cells/microl). In conclusion, the incidence of CMV retinitis was 0.091 per patient-year among study subjects with advanced HIV infection who were receiving HAART (95% confidence interval [CI], 0.037-0.145). The time to progression of CMV retinitis (mean, 215 days; 95% CI, 113-317 days) was longer than reported before widespread use of PIs.

Topics: Adult; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Drug Therapy, Combination; Foscarnet; Ganciclovir; HIV Protease Inhibitors; Humans; Incidence; Indinavir; Nelfinavir; Outcome Assessment, Health Care; Prospective Studies; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir

Because ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, and clarithromycin, a macrolide antibiotic used in the treatment of disseminated infection caused by Mycobacterium avium complex, are likely to be administered concurrently for treatment of patients with HIV and acquired immunodeficiency syndrome (AIDS), the drug interaction potential of these 2 agents was evaluated. Both clarithromycin and ritonavir are metabolized to a significant extent through cytochrome P450-mediated biotransformation and are potential inhibitors of these enzymes.. To evaluate the pharmacokinetic effects of concomitant administration of multiple doses of ritonavir and clarithromycin.. This was an open-label, randomized, 3-period crossover study. Ritonavir alone (200 mg every 8 hours), clarithromycin alone (500 mg every 12 hours), and ritonavir and clarithromycin in combination were administered to 22 healthy volunteers. Blood samples were collected on day 4 for determination of ritonavir, clarithromycin, and its metabolite 14-(R)-hydroxyclarithromycin.. Ritonavir practically completely inhibited the formation of 14-(R)-hydroxyclarithromycin. The mean area under the plasma concentration-time curve (AUC) for clarithromycin increased by 77% with concomitant ritonavir, and the harmonic mean terminal half-life increased from 5 hours to 14 hours. Statistically significant increases in peak plasma concentration (31%) and minimum plasma concentration (182%) were also observed. The effect of concomitant clarithromycin administration on ritonavir pharmacokinetics was statistically significant but small, with a 12.5% increase in mean AUC and a 15.3% increase in peak plasma concentration. The terminal half-life increased from 3.47 to 3.87 hours with concomitant clarithromycin.. No adjustment of the ritonavir dose is necessary when administered with clarithromycin. In addition, no changes in clarithromycin dose are warranted in patients with normal renal function.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Clarithromycin; Cross-Over Studies; Drug Administration Schedule; Drug Interactions; Female; Half-Life; HIV Protease Inhibitors; Humans; Hydroxylation; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Reference Values; Ritonavir

To study the relationship between the CD4+ cell response after initiation of protease inhibitors and the occurrence of opportunistic infections and survival.. Prospective observational cohort study.. HIV-1-seropositive subjects followed-up in HIV centres of Bordeaux University Hospital, Southwest France who were prescribed at least one available protease inhibitor between January and December 1996 were included in this analysis. A Cox model estimated the independent effect of baseline covariates and CD4+ cell response, considered as a time-dependent covariate, on the occurrence of new AIDS-defining opportunistic infection, new AIDS-defining events, new AIDS-defining opportunistic infection or death.. A total of 556 HIV-positive patients were prescribed at least one protease inhibitor: 34% saquinavir, 52% indinavir, and 14% ritonavir. Median CD4+ cell count at baseline was 95 x 10(6)/l and mean plasma HIV RNA was 5.0 log10 copies/ml. After a median follow-up of 230 days, 65 patients experienced a new episode of opportunistic infection, 79 patients experienced at least one AIDS-defining event, and 24 had died. On average, the increase in CD4+ cell count was 42 x 10(6)/l (SD, 74) after a median of 49 days. In the multivariate analysis of opportunistic infection or death, each 50% higher CD4+ cell count at baseline was associated with a 23% reduction [95% confidence interval (CI), 14-30] of risk. Each 50% increase in CD4+ cell count during follow-up was associated with a 9% reduction (95% CI, 2-15) of risk, adjusted for the presence of AIDS prior to protease inhibitor therapy (hazard ratio, 3.76 versus absence of AIDS; P < 0.01) and haemoglobin level (hazard ratio, 0.48 if > 11 g/dl versus <11 g/dl; P < 0.01).. Our results show, at least indirectly, how protease inhibitors might produce clinical stabilization. This result may be due to improved functionality of CD4+ cells in patients started on protease inhibitors.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Cohort Studies; Disease Progression; Female; Follow-Up Studies; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Predictive Value of Tests; Prospective Studies; Risk Factors; Ritonavir; Saquinavir

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Double-Blind Method; HIV Protease Inhibitors; Humans; Male; Middle Aged; Ritonavir; Sarcoma, Kaposi; Treatment Outcome

The HIV protease inhibitor, ritonavir, reduces the risk of death by 43 percent in patients with late-stage AIDS. Study participants were randomized to ritonavir or placebo in a double-blind trial. After the first month of the study, the risk of death or development of an AIDS-defining event was reduced by 58 percent. Risk reduction was seen six months into treatment. The successful data collection in this study was in large part due to the manufacturer entering patients with extremely low CD4 counts; these patients are not eligible for many trials and are at the highest risk for death.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Double-Blind Method; HIV Protease Inhibitors; Humans; Ritonavir; Survivors; Thiazoles; Valine

Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published.. A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter. Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free.. We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.

Topics: AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Antifungal Agents; Antigens, Fungal; Benzoxazines; Child; Cryptococcus neoformans; Cyclopropanes; Dideoxynucleosides; Drug Combinations; Female; Fluconazole; HIV; Humans; Immune Reconstitution Inflammatory Syndrome; Lamivudine; Lopinavir; Meningitis, Cryptococcal; Ritonavir; Treatment Outcome; Viral Load; Zidovudine

This study aimed to assess the pharmacokinetic profile of 150 mg rifabutin (RBT) taken every other day (every 48 h) versus 300 mg RBT taken every other day (E.O.D), both in combination with lopinavir/ritonavir (LPV/r), in adult patients with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection.. This is a two-arm, open-label, pharmacokinetic, randomised study conducted in Burkina Faso between May 2013 and December 2015. Enrolled patients were randomised to receive either 150 mg RBT EOD (arm A, 9 subjects) or 300 mg RBT EOD (arm B, 7 subjects), both associated with LPV/r taken twice daily. RBT plasma concentrations were evaluated after 2 weeks of combined HIV and TB treatment. Samples were collected just before drug ingestion and at 1, 2, 3, 4, 6, 8, and 12 h after drug ingestion to measure plasma drug concentration using an HPLC-MS/MS assay.. This study confirmed that the 150 mg dose of rifabutin ingested EOD in combination with LPV/r is inadequate and could lead to selection of rifamycin-resistant mycobacteria.. PACTR201310000629390, 28th October 2013.

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Burkina Faso; Chromatography, High Pressure Liquid; Coinfection; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Protease Inhibitors; Humans; Lopinavir; Male; Microbial Sensitivity Tests; Pilot Projects; Random Allocation; Rifabutin; Ritonavir; Tandem Mass Spectrometry; Tuberculosis

Topics: AIDS-Related Opportunistic Infections; Amides; Anti-HIV Agents; Cardiovascular Diseases; Clinical Trials, Phase II as Topic; Darunavir; Disease Management; Disease Susceptibility; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Male; Penis; Piperazines; Pyridones; Ritonavir; Treatment Outcome; Washington

We aimed to investigate the efficacy of interferon and ribavirin-free sofosbuvir/ledipasvir (SOF/LDV) and ritonavir boosted paritaprevir/ombitasvir with or without dasabuvir (2D/3D) regimens in a real-life cohort of human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected patients. The study focused on efficacy, need for changes in antiretroviral therapy (ART) due to drug-drug interaction (DDI), and treatment-associated changes in liver stiffness.. In this study 36 patients (n = 21 SOF/LDV and n = 15 2D/3D) were retrospectively analyzed. Depending on the genotype the following treatment regimens were used: HCV genotype (GT)-1: either SOF/LDV or 3D, no patient with HCV-GT2 was included, HCV-GT3: SOF/LDV, HCV-GT4: 2D.. Approximately one third (35.3%) of patients were treatment-experienced and 13.9% had cirrhosis. Antiretroviral therapy had to be changed in 38.1% of SOF/LDV and 60% of 2D/3D patients prior to anti-HCV treatment due to expected DDIs. We observed sustained virologic response (SVR) rates of 100% in patients treated with SOF/LDV (19/19) and 2D/3D (14/14). One 2D/3D patient was lost to follow-up, while two SOF/LDV patients died during therapy from non-treatment-related causes. They were excluded from the analysis. Between baseline and follow-up liver stiffness decreased from 11.4 to 8.3 kPa (p = 0.008) and from 8.1 to 5.7 kPa (p = 0.001) in SOF/LDV and 2D/3D patients, respectively.. We confirmed the excellent HCV eradication rates >95% in a real-life cohort of HIV/HCV coinfected patients treated with SOF/LDV and 2D/3D. We observed no HCV relapse or breakthrough. More patients treated with 2D/3D required a change in ART than patients treated with SOF/LDV. Additionally, HCV eradication led to a rapid decline in liver stiffness.

Topics: 2-Naphthylamine; Adult; AIDS-Related Opportunistic Infections; Anilides; Anti-HIV Agents; Antiviral Agents; Austria; Benzimidazoles; Carbamates; Cohort Studies; Cyclopropanes; Drug Therapy, Combination; Female; Fluorenes; Hepatitis C, Chronic; HIV Seropositivity; Humans; Lactams, Macrocyclic; Liver; Liver Cirrhosis; Macrocyclic Compounds; Male; Middle Aged; Proline; Retrospective Studies; Ritonavir; Sofosbuvir; Sulfonamides; Uracil; Uridine Monophosphate; Valine

Incidence of brain infections in Human Immunodeficiency Virus (HIV) positive patients is reduced after the availability of current high active antiretroviral therapy (HAART). Herpes Simplex Virus type 2 (HSV-2) is an infrequent cause of encephalitis in HIV patients despite it is frequently involved in sexual transmitted infections. Here, we report a case of HSV-2 encephalitis occurring in a patient without full suppression of HIV replication within the brain. A 38 year-old HIV infected man was admitted to our department because of recurrent generalized seizure and fever during the previous 24 hours. Eight months before our observation the patient was switched from a protease inhibitor based regimen to a rilpivirine-based regimen without any evidence of HIV-RNA replication in the plasma. When the patient was admitted in our hospital, he was febrile and moderately confused, no deficit of cranial nerves was reported, motility was conserved, but he was unable to walk. Laboratory examinations performed at admission demonstrated an increase of cerebrospinal fluid (CSF) protein and cells with lymphocyte prevalence, and normal CSF glucose. HSV-2-DNA and HIV-RNA were present within CSF at admission. Nuclear Magnetic Resonance imaging of the brain revealed lesions of the medial part of both temporal lobes including hippocampus without any sign of bleeding. A 21-day course of acyclovir therapy was administered with consistent improvement of clinical findings and disappearance of HSV-2-DNA within CSF. After the episode, HAART was switched to a regimen with high CSF penetrability containing abacavir, lamivudine, darunavir and ritonavir. Twelve months after HSV-2 encephalitis neurologic evaluation was normal, but symptoms of depression were reported, HIV-RNA remained undetectable both in the plasma and CSF, and CD4+ lymphocytes were above 500/μL. No opportunistic infection was reported. Patients switched to regimen well tolerated such those containing rilpivirine, that have poor drug concentration within CSF could be considered at risk for opportunistic infection of the brain. Further larger investigation needs to confirm this finding.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Darunavir; Dideoxynucleosides; Drug Substitution; Encephalitis, Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Male; Rilpivirine; Ritonavir; Virus Replication

We report an unusual case of pulmonary aspergillosis in a patient with AIDS and we demonstrated the drug-drug interactions between voriconazole, darunavir/ritonavir and tenofovir/emtricitabine. The combination darunavir-ritonavir-voriconazole should be avoided.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antifungal Agents; Aspergillosis; Aspergillus; Darunavir; Drug Interactions; Emtricitabine; HIV Infections; HIV Protease Inhibitors; Humans; Lung Abscess; Male; Ritonavir; Tenofovir; Treatment Outcome; Voriconazole

Topics: Abscess; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Axilla; Clarithromycin; Darunavir; Dideoxynucleosides; Enfuvirtide; Ethambutol; HIV Envelope Protein gp41; HIV-1; Humans; Immune Reconstitution Inflammatory Syndrome; Isoniazid; Lamivudine; Lymph Node Excision; Lymphadenitis; Male; Mycobacterium avium-intracellulare Infection; Peptide Fragments; Pyrazinamide; Rifampin; Ritonavir; Streptomycin; Sulfonamides

The population pharmacokinetics (PK) of lopinavir in tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected South African children taking super-boosted lopinavir (lopinavir/ritonavir ratio 1:1) as part of antiretroviral treatment in the presence of rifampicin were compared with the population PK of lopinavir in HIV-infected South African children taking standard doses of lopinavir/ritonavir (ratio 4:1).. Lopinavir concentrations were measured in 15 TB/HIV-co-infected paediatric patients who were sampled during and after rifampicin-based TB treatment and in 15 HIV-infected children without TB. During TB therapy, the dose of ritonavir was increased to lopinavir/ritonavir 1:1 in order to compensate for the induction of rifampicin. The children received median (interquartile range=IQR) doses of lopinavir 292 mg/m(2) (274, 309) and ritonavir 301 mg/m(2) (286, 309) twice daily. After TB treatment completion the children received standard doses of lopinavir/ritonavir 4:1 (median [IQR] lopinavir dose 289 mg/m(2) [286, 303] twice daily) as did those without TB (median [IQR] lopinavir dose 265 mg/m(2) [249, 289] twice daily).. Lopinavir oral clearance (CL/F) was about 30% lower in children without TB than in co-infected children treated with super-boosted lopinavir. However, the predicted lopinavir C(min) was above the recommended minimum therapeutic concentration during TB/HIV co-treatment in the 15 children. Lopinavir CL/F increased linearly during the dosing interval.. Increasing the ritonavir dose to achieve a lopinavir/ritonavir ratio of 1:1 when given in combination with rifampicin-based TB treatment did not completely compensate for the enhancement of lopinavir CL/F caused by rifampicin. The time-dependent lopinavir CL/F might be due to a time-dependent recovery from ritonavir inhibition of lopinavir metabolism during the dosing interval.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Infant; Lopinavir; Male; Pyrimidinones; Rifampin; Ritonavir; South Africa; Time Factors; Treatment Outcome; Tuberculosis, Pulmonary

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; CD4-Positive T-Lymphocytes; Hepatitis C, Chronic; Histiocytes; Humans; Lamivudine; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Lopinavir; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Patient Compliance; Pentamidine; Pyrimidinones; Recurrence; Ritonavir; Tattooing; Zidovudine

Tuberculosis (TB) is a common opportunistic infection among HIV-infected people, and rifampicin is an important drug for the treatment of TB. However, administration of rifampicin in combination with antiretroviral therapy, particularly protease inhibitors, is difficult because of drug-drug interactions.. We have performed a prospective study in three HIV-infected patients with TB treated with a rifampicin-containing regimen (rifampicin 600 mg per day) and antiretroviral therapy including only nucleoside reverse transcriptase inhibitors (NRTIs) plus atazanavir 300 mg once a day (qd) and ritonavir 100 mg qd, to evaluate whether the inducing effect of rifampicin on the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 could be overcome by the inhibitory effect of ritonavir. A complete pharmacokinetic evaluation of the steady-state concentrations of atazanavir and ritonavir was performed.. In all three cases, more than 50% of the time the atazanavir level was below the minimum recommended trough plasma level (150 ng/mL according to current pharmacokinetic guidelines) to inhibit HIV wild-type replication.. These results strongly indicate that the administration of rifampicin with a combination of atazanavir 300 mg qd plus ritonavir 100 mg qd must be avoided because subtherapeutic concentrations of atazanavir are produced.

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Area Under Curve; Atazanavir Sulfate; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Drug Interactions; Drug Therapy, Combination; Female; HIV Protease Inhibitors; Humans; Male; Oligopeptides; Prospective Studies; Pyridines; Rifampin; Ritonavir; Tuberculosis

Topics: AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Developing Countries; Drug Therapy, Combination; HIV Protease Inhibitors; Humans; Rifampin; Ritonavir; Saquinavir; Tuberculosis

Topics: Adult; AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Antitubercular Agents; Benzoxazines; Cyclopropanes; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Oxazines; Ritonavir; Treatment Outcome; Tuberculosis, Pulmonary

Cryptococcus neoformans is an opportunistic pathogen that can manifest in immunocompromised patients with acquired immune deficiency syndrome. Prevention of cryptococcosis and other opportunistic diseases is an objective in the management of human immunodeficiency virus (HIV)-infected patients. The goal of highly active antiretroviral therapy (HAART) is to reduce the viral loads and enhance CD4 counts in HIV-infected patients. These 2 mechanisms keep HIV-infected patients healthier and enhance their immune systems, thus reducing and often preventing opportunistic infections such as ocular cryptococcal infections. Discontinuation of HAART can lead to ocular opportunistic infections such as cryptococcal choroiditis.. Presented here is a case of a patient who was treated successfully with HAART of stavudine (D4T), abacavir (Ziagen), ritonavir (Norvir), and saquinavir (Invirase). His last CD4 count before HAART was discontinued was 131 cells/mm(3), and viral load was less than 50 copies/mL. He discontinued his HAART regimen for 2 years and presented to the emergency room with complaints of a severe headache with neck pain, lightheadedness, nausea, disorientation, and unsteady gait. Lumbar puncture results showed cryptococcal infection, and the patient was admitted for the treatment of cryptococcal meningitis with amphotericin B and 5-flucytosine. Cryptococcal choroiditis was diagnosed after treatment of the meningitis. After resolution, his resultant visual acuities were 10/350 in the right eye and 10/600 in the left eye. He is on a maintenance dose of antifungal therapy and has been reinitiated on HAART of abacavir/zidovudine/lamivudine (Trizivir) and lopinavir/ritonavir (Kaletra).. This case exemplifies the importance of HAART in the prevention of opportunistic infections, cryptococcal meningitis/choroiditis in particular. Eye care professionals can play a role in encouraging patients to comply with their HAART regimens.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Choroiditis; Cryptococcus neoformans; Dideoxynucleosides; Eye Infections, Fungal; Follow-Up Studies; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Ritonavir; Saquinavir; Stavudine

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Antiretroviral Therapy, Highly Active; Bronchoalveolar Lavage Fluid; Bronchoscopy; HIV Infections; HIV Protease Inhibitors; Humans; Nelfinavir; Pneumocystis carinii; Pneumocystis Infections; Pyridines; Pyrones; Ritonavir; Saquinavir; Sulfonamides

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antiretroviral Therapy, Highly Active; CD4-Positive T-Lymphocytes; Fluconazole; Flucytosine; HIV Infections; Humans; Immunologic Memory; Lamivudine; Lopinavir; Male; Meningitis, Cryptococcal; Pyrimidinones; Recurrence; Ritonavir; Syndrome; T-Lymphocyte Subsets; Zidovudine

We describe a drug-drug interaction between coformulated lopinavir/ritonavir and itraconazole in a patient infected with human immunodeficiency virus type 1 who had disseminated histoplasmosis. Coadministration of these agents led to a strong increase in itraconazole concentrations and a decrease in concentrations of its metabolite, hydroxyitraconazole, which is equally active pharmacologically. The dosage of itraconazole was reduced when it was used in combination with lopinavir/ritonavir.

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Antiretroviral Therapy, Highly Active; Drug Interactions; Drug Therapy, Combination; Histoplasmosis; HIV Infections; HIV Protease Inhibitors; Humans; Itraconazole; Lopinavir; Male; Middle Aged; Pyrimidinones; Ritonavir

To determine the incidence of significant liver enzyme elevations following the initiation of protease inhibitor (PI)-based antiretroviral therapy (ART) with or without pharmacokinetic boosting with ritonavir (RTV), and to define the role of chronic viral hepatitis in its development.. Prospective, cohort analysis of 1161 PI-naive, HIV-infected patients receiving RTV-boosted (lopinavir, indinavir and saquinavir) and unboosted PI-based ART (indinavir, nelfinavir) that had at least one liver enzyme measurement before and during therapy.. The incidence of grade 3 and 4 liver enzyme elevations among persons with and without hepatitis B and/or C co-infection treated with PI-based ART were compared. Severe hepatotoxicity was defined as an increase in serum liver enzyme >/= 5-times the upper limit of the normal range or 3.5-times an elevated baseline level.. The incidence of grade 3 or 4 elevations among PI-naive patients was: nelfinavir, 11%; lopinavir/RTV (200 mg/day), 9%; indinavir, 13%; indinavir/RTV (200-400 mg/day), 12.8%; and saquinavir/RTV (800 mg/day), 17.2%. The risk was significantly greater among persons with chronic viral hepatitis (63% of cases); however, the majority of hepatitis C virus (HCV)-infected patients treated with nelfinavir (84%), saquinavir/RTV (74%), indinavir, 86%, indinavir/RTV (90%) or lopinavir/RTV (87%) did not develop hepatotoxicity.. Our data suggest that the lopinavir/RTV is not associated with a significantly increased risk of hepatotoxity among HCV-infected and uninfected patients compared with an alternative PI-based regimen, nelfinavir. Accordingly, other medication-related factors (e.g, efficacy and non-hepatic toxicity) should guide individual treatment decisions.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Chronic Disease; Drug Therapy, Combination; Female; Hepatitis; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Liver; Lopinavir; Male; Nelfinavir; Prospective Studies; Pyrimidinones; Reverse Transcriptase Inhibitors; Risk Factors; Ritonavir; Saquinavir; Treatment Outcome

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Clarithromycin; Drug Combinations; HIV Protease Inhibitors; HIV Seropositivity; Humans; Lopinavir; Nutrition Disorders; Patient Care Management; Physician-Patient Relations; Pyrimidinones; Quality of Life; Ritonavir

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antiprotozoal Agents; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Leishmaniasis; Lopinavir; Male; Pyrimidinones; Renal Dialysis; Renal Insufficiency; Ritonavir

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; CD4 Lymphocyte Count; Consumer Product Safety; Drug Therapy, Combination; HIV Protease Inhibitors; HIV-1; Humans; Pilot Projects; Pyrazinamide; Rifampin; Ritonavir; RNA, Viral; Tuberculosis; Viral Load

A clinical syndrome represented by the association of Mycobacterium avium complex (MAC) infection with initiation of highly active antiretroviral therapy (HAART) has been recently described in patients with advanced HIV disease. HAART-associated improvement of the immune status might convert a clinically silent MAC infection into an active mycobacterial disease. A 40-year-old man with severe factor VII deficiency, advanced HIV-1 disease, a CD4 + lymphocyte count of 15 cells microL-1 (CDC stage A3) and 470,000 HIV-RNA copies mL-1 (measurement by NASBA system) underwent standard HAART (lamivudine, stavudine and ritonavir). Two weeks after HAART onset, the patient developed enlargement of the lymph nodes throughout the mesentery and after seven weeks a rapidly enlarging mass on the left side of the neck. Culture from a needle aspirate specimen revealed MAC. His CD4 + count had increased to 97 cells microL-1 and viraemia dropped to undetectable HIV-RNA copies. While continuing antiviral therapy, multidrug therapy for MAC infection (clarithromycin, ciprofloxacin, ethambutol, amikacin) was started with progressive improvement and cure of the neck mycobacterial infection and disappearance of the abdominal lymph nodes. HAART has been shown to offer significant clinical and laboratory benefits in terms of HIV disease with limited side-effects in Haemophiliacs. However, the clinical manifestation of an opportunistic infection should be mentioned as a possible complication of HAART in these patients, as well as in other categories of HIV infected patients, and in patients with congenital coagulopathies.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Factor VII Deficiency; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lamivudine; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Reverse Transcriptase Inhibitors; Ritonavir; Stavudine

To determine the relationship between antiretroviral therapy and changes in prevalence and amount of oropharyngeal candidiasis (OPC) and skin test reactivity for delayed type hypersensitivity.. Observational cohort.. University-based public hospital AIDS clinic.. Adults with advanced HIV infection who had been taking nucleoside transcriptase inhibitor drugs but had not taken a protease inhibitor and who started antiretroviral treatment with ritonavir.. OPC lesions score, oral candidal colonization, oral candidal quantification, skin test reactivity for delayed type hypersensitivity (purified protein derivative, candidal and streptokinase antigens), plasma HIV RNA and CD4 cell count at weeks 8, 16 and 48 weeks.. In the 99 patients who entered the study, there was a significant reduction in the HIV plasma RNA (mean log decrease from baseline at 48 weeks 0.88) and a significant increase in CD4 cell counts (mean CD4 cell increase from baseline at 48 weeks 128 x 10(6) cells/l). Only 17% of patients had < 200 copies/ml HIV RNA at 48 weeks. There were significant decreases in the prevalence of OPC lesions (31% at baseline to 1% at 48 weeks; P < 0.001), and in oral candidal loads [2226 to 811 colony-forming units (CFU)/ml; P = 0.0171]. The percentage of patients with at least one positive skin test increased significantly (6 to 28%; P < 0.05). Patients whose CD4 lymphocyte count was > 200 x 10(6) cells/l at 48 weeks had significantly lower oral candidal loads and were more likely to have a positive skin test than patients whose CD4 cell count was < 200 x 10(6) cells/l.. In patients with advanced HIV infection, antiretroviral treatment including a protease inhibitor has a positive impact in the natural history of OPC. This positive impact appears to be correlated with a better immunological function and occurs despite continuous HIV replication.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Candida; Candidiasis, Oral; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hypersensitivity, Delayed; Male; Middle Aged; Oropharynx; Reverse Transcriptase Inhibitors; Ritonavir; RNA, Viral

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Drug Administration Schedule; HIV Protease Inhibitors; Humans; Indinavir; Odds Ratio; Ritonavir; Saquinavir; Spain; Survival Analysis; Treatment Failure; Treatment Outcome

A 30-year-old man with a known HIV infection for 7 years presented for treatment with antiretroviral drugs. He was known to have had herpes zoster, oral hairy leukoplakia and recurrent Candida stomatitis, but was otherwise without symptoms.. The CD4 lymphocyte count was 19 cells/mm3 and there were 41,000 HIV-RNA copies/ml.. The HIV infection was in CDC stage B3, indicating the need for combined antiretroviral treatment. A week after starting stavudine, saquinavir and ritonavir he had to be admitted because of nausea and vomiting, colicky abdominal pain, diarrhea, fever up to 39 degrees C and a rise of C-reactive protein to 207 mg/dl. Bacteriological examination of feces and biopsy of an enlarged retroperitoneal lymph node revealed atypical mycobacteria. Antituberculosis treatment was started. The CD4 cell count rose to 56/mm3 and the viral count fell to 11,000/ml. Each time after initiating a different antiviral regimen the symptoms recurred.. This case illustrates an atypical manifestation of on opportunistic infection: during combined antiviral treatment the CD4 cell count rose and thus precipitated an heretofore subclinical mycobacterial infection with focal lymphadenitis. If, on starting antiretroviral treatment at a late HIV stage, new symptoms develop within 1-3 weeks, one should consider drug-induced side effects or the onset of an opportunistic infection that has become manifest as the result of an improved immunological state.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Diagnosis, Differential; Drug Therapy, Combination; Follow-Up Studies; HIV Infections; HIV Protease Inhibitors; Humans; Lymphadenitis; Male; Mesenteric Lymphadenitis; Mycobacterium avium-intracellulare Infection; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir; Stavudine; Time Factors; Tuberculosis

Topics: AIDS-Related Opportunistic Infections; Candida albicans; Candidiasis; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir

Topics: Adult; AIDS-Related Opportunistic Infections; Alanine Transaminase; Hepatitis B, Chronic; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir

Highly active antiretroviral therapy that includes human immunodeficiency virus (HIV) aspartyl protease inhibitors (PIs) causes a decline in the incidence of some opportunistic infections in AIDS, and this decline is currently attributed to the restoration of specific immunity. The effect of two PIs (indinavir and ritonavir) on the enzymatic activity of a secretory aspartyl protease (Sap) of Candida albicans (a major agent of mucosal disease in HIV-infected subjects) and on growth and experimental pathogenicity of this fungus was evaluated. Both PIs strongly (>/=90%) and dose dependently (0.1-10 microM) inhibited Sap activity and production. They also significantly reduced Candida growth in a nitrogen-limited, Sap expression-dependent growth medium and exerted a therapeutic effect in an experimental model of vaginal candidiasis, with an efficacy comparable to that of fluconazole. Thus, besides the expected immunorestoration, patients receiving PI therapy may benefit from a direct anticandidal activity of these drugs.

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Aspartic Acid Endopeptidases; Candida albicans; Candidiasis, Oral; Candidiasis, Vulvovaginal; Female; HIV Protease Inhibitors; Humans; Indinavir; Pepstatins; Protease Inhibitors; Rats; Ritonavir

Topics: AIDS-Related Opportunistic Infections; Hepacivirus; Hepatitis C; HIV Protease Inhibitors; Humans; Immunity; Indinavir; Retrospective Studies; Ritonavir; Saquinavir

To evaluate the clinical and biological impact of protease inhibitors on HIV-associated Kaposi's sarcoma.. A cohort of 10 patients included prospectively from April 1996 to June 1997 were studied in one institutional centre after initiation of protease inhibitors.. All patients but one (stable disease) had progressive Kaposi's sarcoma. Three out of 10 patients had stopped specific chemotherapy for Kaposi's sarcoma for more than 4 weeks, three were still under chemotherapy, and four had never received specific treatment of Kaposi's sarcoma. Plasma HIV viral load, human herpesvirus (HHV)-8 viraemia in peripheral blood mononuclear cells (PBMC), and CD4 cell count were sequentially assessed from the beginning of therapy. For six patients, a semiquantitative evaluation of HHV-8 viral load in the Kaposi's sarcoma lesions was performed during treatment using polymerase chain reaction.. After initiation of HIV triple therapy with protease inhibitors, we observed six complete responses, two partial responses, and two patients with progressive disease. All patients had undetectable plasma HIV viral load within 2 months of treatment. Undetectable HHV-8 viraemia in PBMC occurred in seven out of eight patients with partial or complete response and in none of the progressive patients. A decrease or negation of HHV-8 viral load in Kaposi's sarcoma lesions was observed in two complete responders.. Our results suggest that antiviral therapy with protease inhibitors are clinically efficient in HIV-associated Kaposi's sarcoma and that there exists a correlation between clinical response and negation of HHV-8 viraemia.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Didanosine; Dideoxynucleosides; Drug Therapy, Combination; Female; Herpesvirus 8, Human; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Male; Middle Aged; Prospective Studies; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir; Sarcoma, Kaposi; Stavudine; Treatment Outcome; Viral Load; Viremia; Zalcitabine; Zidovudine

Uveitis is an ocular manifestation rarely observed in HIV-infected patients. We observed three cases of anterior uveitis without progressive retinitis in HIV patients receiving antiprotease treatment.. The first patient developed a first episode of uveitis during ritonavir therapy. Two other episodes occurred with indinavir. The second patient developed uveitis when treated with indinavir. In the third patient, the first episode developed with indinavir and a second with a ritonavir-saquinavir combination. Uveitis was unilateral in 4 episodes. Clinical manifestations were red irritable eyes and, in 2 episodes, reduced visual acuity. The antiprotease was interrupted in 4 of the 6 episodes and clinical course was rapidly favorable.. Pure anterior uveitis should suggest drug induction in HIV infected patients; rifabutin is often the cause. Infectious causes predominate in case of total uveitis associating choroid and retinal involvement. Cytomegalovirus, herpes zoster, syphilis, and toxoplasmosis have been incriminated. Antiproteases would appear to be a new cause of anterior uveitis in HIV-infected patients.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Drug Combinations; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Middle Aged; Rifabutin; Ritonavir; Saquinavir; Uveitis; Uveitis, Anterior; Visual Acuity

To analyse the characteristics of opportunistic infections in patients receiving highly active antiretroviral treatment (HAART).. A retrospective study performed in seven hospitals, included all patients starting treatment by ritonavir or indinavir between 26 March and 31 December 1996. Patients were evaluated for the development of AIDS-defining events. Clinical evaluation, plasma HIV-1 RNA quantification, CD4 cell count were recorded at baseline and at the onset of the event.. Four hundred and eighty-six patients were included: 44.2% had a CD4 cell count below 50 x 10(6) cells/l. Fifty clinical events were recorded in 46 patients with a mean follow-up of 6.1 months, of which 34 events (68%) were observed during the first 2 months of HAART. Eighteen of these occurred despite a reduction of viral load by at least 1.5 log10) and a 100% increase of the CD4 cell count compared with that at the onset of the event, corresponding to 11 cytomegalovirus infections, five mycobacterial infections, one case of cryptococcosis, and one case of Varicella-Zoster virus-related acute retinal necrosis. Among the 16 events observed after the second month, six occurred despite a marked biological improvement, corresponding to a recurrence in five of six patients who had stopped their maintenance therapy. Events were one cytomegalovirus infection, two mycobacterial infections, one episode of oesophageal candidiasis and one cryptococcal meningitis.. In patients at high risk of developing an opportunistic infection prior to the institution of a HAART regimen, prophylaxis should not be discontinued during the first 2 months of treatment, and maintenance therapy should be carried on despite a significant increase in the CD4 cell count.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Candidiasis; CD4 Lymphocyte Count; Cryptococcosis; Cytomegalovirus Infections; Disease Progression; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; HIV-1; Hospitals, University; Humans; Indinavir; Mycobacterium Infections; Pneumonia, Pneumocystis; Retrospective Studies; Ritonavir; RNA, Viral; Toxoplasmosis, Cerebral; Viral Load

To report observations from case studies on the pathogenic mechanisms underlying the acute hepatitis that sometimes occurs in hepatitis C virus (HCV) and HIV coinfected patients following treatment with potent antiretroviral therapy that includes a HIV protease inhibitor.. Cases of acute hepatitis were identified from a group of 133 patients enrolled in a retrospective study of pathogen-associated inflammatory disease following the use of potent antiretroviral therapy. Data on serum alanine aminotransferase concentrations, clinical events, HCV antibodies, and liver biopsies were collected from medical records. HCV RNA assays and additional HCV antibody assays were undertaken on stored plasma or sera.. Three of the 133 patients (2%) developed symptomatic hepatitis. One was HCV antibody-positive prior to commencing antiretroviral therapy and developed hepatitis subsequent to an episode of Mycobacterium avium complex disease associated with immune restoration. However, the other two patients had previously undiagnosed HCV infection for up to 2 years prior to antiretroviral therapy, with HCV RNA detected but anti-HCV antibody repeatedly undetectable in stored plasma or sera. HCV antibody was only detectable after antiretroviral therapy-induced decrease in plasma HIV RNA and immunological reconstitution. Plasma HCV RNA increased after therapy in one of these patients, but in the other the level was not increased at a time of active hepatitis demonstrated by liver biopsy.. Hepatitis in HCV-HIV-coinfected patients following treatment with potent antiretroviral therapy may reflect restoration of anti-HCV immune responses rather than increased HCV replication or a hepatotoxic effect of antiretroviral therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Female; Hepacivirus; Hepatitis C; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Male; Retrospective Studies; Reverse Transcriptase Inhibitors; Ritonavir; Stavudine

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Antiviral Agents; Cidofovir; Clinical Trials as Topic; Cytomegalovirus Retinitis; Cytosine; HIV Infections; Humans; Isoquinolines; Nelfinavir; Nevirapine; Organophosphonates; Organophosphorus Compounds; Protease Inhibitors; Pyridines; Ritonavir; Sulfonic Acids

Topics: Adult; AIDS-Related Opportunistic Infections; Carrier State; CD4 Lymphocyte Count; Hepatitis B; HIV Infections; HIV Protease Inhibitors; Humans; Immunity; Male; Ritonavir

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Humans; Male; Molluscum Contagiosum; Photography; Remission Induction; Ritonavir

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiviral Agents; DNA, Viral; Herpesvirus 8, Human; HIV Protease Inhibitors; Humans; Male; Mouth Neoplasms; Ritonavir; Sarcoma, Kaposi; Skin Neoplasms

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-HIV Agents; Diarrhea; Follow-Up Studies; HIV Protease Inhibitors; Humans; Indinavir; Intestinal Diseases, Parasitic; Male; Microsporida; Microsporidiosis; Remission Induction; Retrospective Studies; Ritonavir

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Delavirdine; Diarrhea; Didanosine; Drug Interactions; Drug Therapy, Combination; HIV Infections; Humans; Indinavir; Lamivudine; Nelfinavir; Nevirapine; Protease Inhibitors; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir; Virus Replication; Zalcitabine; Zidovudine

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; HIV Protease Inhibitors; Humans; Male; Mouth Mucosa; Mouth Neoplasms; Ritonavir; Saquinavir; Sarcoma, Kaposi

Cytomegalovirus (CMV) retinitis is the most common opportunistic viral infection in acquired immunodeficiency syndrome (AIDS) patients with a low CD4+ count. Without specific treatment, the disease is an important cause of blindness. We report two cases of AIDS with nonprogressive CMV retinitis after undergoing a combined antiHIV treatment schedule including at least one protease inhibitor. The treatment was associated with an increase in circulating CD4+ lymphocytes. This newly available antiviral combination may well prevent the recurrence of CMV disease and decrease the morbidity of CMV retinitis.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Drug Therapy, Combination; Fundus Oculi; Ganciclovir; HIV Protease Inhibitors; Humans; Lamivudine; Male; Ritonavir; Saquinavir

Many treatments highlighted at the ICAAC conference were designed to suppress the replication of HIV completely, but growing numbers of people are reporting rebound increases after initial decreases in viral load. However, new drugs are being developed which may be more effective, better tolerated, and less likely to lead to resistance. Agouron Pharmaceuticals has opened an expanded access program for its new protease inhibitor, Viracept; the program is open to people who cannot tolerate the other approved drugs. Gilead Sciences is warning physicians and patients that cidofovir should not be used with other kidney-toxic drugs.

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cidofovir; Cytomegalovirus Retinitis; Cytosine; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Isoquinolines; Kidney; Mutation; Nelfinavir; Organophosphonates; Organophosphorus Compounds; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir; Sulfonic Acids; Treatment Failure; Viral Load