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At least 433 records · Page 24Linked to original sources
PubMed1994

Control of the body burden of M. avium complex is associated with improved quality of life and prolonged survival of patients with AIDS: a prospective trial with rifabutin combined with isoniazid, clofazimine, ethambutol.

The objectives of this study were to assess whether culture conversion affects quality of life (QoL), survival and Mycobacterium avium complex (MAC)-associated morbidity in patients with AIDS. Data from an open, multicenter, noncomparative trial were analyzed to test the benefit of suppressing mycobacteria: measures of QoL, clinical outcomes and quality-adjusted survival are compared on occasion of culture-negative and positive assessments. The study was conducted at AIDS clinics in France, coordinated by the GETIM, with the participation of 51 AIDS patients with culture-proven Non-Tuberculous Mycobacteria (NTM) disease. Patients underwent a quadruple drug-regimen. The following parameters were investigated: (i) Culture conversion to a negative finding (= suppression) or on > 2 occasions, including each patient's last valid observation (= conversion); (ii) survival after treatment start; (iii) QoL by using the ECOG score, re-coded 0 to 4 for worst to best performance status; (iv) quality-adjusted survival. On treatment, > 1 negative culture was recorded for 69% of the evaluable patients, corresponding to 111 person-months of observation. Positive culture findings accounted for 42 person-months only. Patients' performance status (mean 1.8 at entry) worsened or improved according to whether culture was positive or negative (means 1.2 and 2.2; total scores 109 and 217 person-months, respectively). Similarly, MAC-attributable morbidity was significantly reduced when culture was negative. Mean survival was 195 days longer in treatment success patients. These analyses suggest that, in patients with NTM disease occurring as a late complication of AIDS, treatment was effective in improving clinical status and survival, and in suppressing bacterial growth.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1999

Heterodimer-loaded erythrocytes as bioreactors for slow delivery of the antiviral drug azidothymidine and the antimycobacterial drug ethambutol.

Disseminated infection with Mycobacterium avium complex (MAC) remains the most common serious bacterial infection in patients with advanced AIDS. The organisms that make up this complex are found ubiquitously in the environment, yet rarely cause disseminated disease in nonimmunocompromised human patients; on the contrary, up to 50% of patients with AIDS may ultimately develop the pathology. Hence, therapeutic strategies able to inhibit HIV and Mycobacterium replication are needed. Because of the rapid plasma elimination and toxicity of the most commonly used drugs, daily multiple-drug therapies must often be continued throughout life, frequently causing major side effects and, as a consequence, poor patient compliance. Therefore, alternative strategies that reduce the toxicity of the drugs and allow prolonged application intervals are sorely needed. Since erythrocytes (RBCs) can behave as bioreactors able to convert impermeant prodrugs to membrane-releasable active drugs, new compounds (AZTpEMB, AZTpEMBpAZT, and AZTp2EMB) consisting of both an antiretroviral and an antimicrobial drug were designed and synthesized. Among these, only AZTp2EMB was hydrolyzed by erythrocyte enzymes and could be encapsulated inside RBCs. AZTp2EMB-loaded RBCs slowly released AZT and EMB in culture medium, reducing its concentration by one-half about every 48 hr of incubation at 37 degrees C. Moreover, when AZTp2EMB-loaded erythrocytes were incubated for 6 days in the presence of human macrophages infected with Mycobacterium avium (M. avium) a marked bactericidal effect (>1 log) was observed. Thus, AZTp2EMB-loaded erythrocytes could be used as endogenous bioreactors for AZT and EMB delivery in the treatment of HIV and M. avium infection.

Anti-HIV Agents↗