ritonavir and Pneumonia--Pneumocystis

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

Up to 50% of patients with severe immune deficiency experience an excessive inflammatory response called immune reconstitution inflammatory syndrome (IRIS) after the initiation of antiretroviral therapy (ART). IRIS has been observed after various opportunistic infections with pathogens such as mycobacteria, including Bacille Calmette-Guérin, cryptococci, human herpesvirus-8, non-Hodgkin's lymphoma, and progressive multifocal leukoencephalopathy. Non-acquired immune deficiency-defining illnesses can also deteriorate after commencement of ART. Renal IRIS has been reported in a few patients with mycobacterial infections, but to the best of our knowledge no cases of nephrotic syndrome and IRIS have been described.. We report the case of an infant with human immunodeficiency virus-1 (HIV-1) infection, Pneumocystis pneumonia, and encephalopathy. During immune reconstitution the patient developed nephrotic syndrome. Treatment of nephrotic syndrome was initiated with prednisone, an angiotensin-converting enzyme inhibitor (lisinopril), and low-molecular-weight heparin. ART was continued, but only a low level of lopinavir/ritonavir could be achieved. There was no relapse of nephrotic syndrome during 10 months of follow-up.. Nephrotic syndrome may occur in infants during immune reconstitution and should not be overlooked.

Topics: Anti-Retroviral Agents; Brain Diseases; Drug Combinations; HIV Infections; HIV-1; Humans; Immune Reconstitution Inflammatory Syndrome; Infant; Lopinavir; Nephrotic Syndrome; Pneumonia, Pneumocystis; Ritonavir

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