minocycline and Acquired-Immunodeficiency-Syndrome

Patients with the HIV infection are at high risk for developing depression. The aim of this study was to investigate the safety and efficacy of antidepressant effects of minocycline on HIV patients with depression. Forty-six HIV patients, with mild-to-moderate depression and a Hamilton Depression Rating Scale (HDRS) up to 18, participated in a parallel, randomized, double-blind, placebo-controlled trial and underwent 6 weeks of treatment with either minocycline (100 mg twice daily) or placebo in the same manner. Patients were assessed using HDRS at baseline and at weeks 3 and 6. The primary outcome measure was to evaluate the efficacy of minocycline in improving depressive symptoms. General linear model repeated measures showed significant effect for time × treatment interaction on the HDRS score during the trial course [F(2, 88)=7.50, P=0.001]. There was no significant difference between the two groups regarding adverse events. No serious adverse event was reported. The administration of 100 mg minocycline twice daily seems to be safe and effective in improving depressive symptoms in HIV/AIDS patients with mild-to-moderate depression.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Anti-Bacterial Agents; Antidepressive Agents; Depression; Double-Blind Method; Female; HIV Infections; Humans; Linear Models; Male; Middle Aged; Minocycline; Treatment Outcome; Young Adult

Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, "Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment," minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), glutamate, neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers.These results suggest that minocycline may decrease lipid markers of oxidative stress (ceramides) in individuals with HAND; however, an effect of minocycline on other CSF markers was not observed. A larger sample size is needed to further validate these results.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; AIDS Dementia Complex; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Ceramides; Cytokines; Double-Blind Method; Female; Glutamic Acid; HIV-1; Humans; Kynurenine; Male; Middle Aged; Minocycline; Neurofilament Proteins; Neurons; Neuroprotective Agents; Nitric Oxide Synthase Type II; Oxidative Stress

Despite the advent of highly active anti-retroviral therapy HIV-associated neurocognitive disorders (HAND) continue to be a significant problem. Furthermore, the precise pathogenesis of this neurodegeneration is still unclear. The objective of this study was to examine the relationship between infection by the simian immunodeficiency virus (SIV) and neuronal injury in the rhesus macaque using in vivo and postmortem sampling techniques. The effect of SIV infection in 23 adult rhesus macaques was investigated using an accelerated NeuroAIDS model. Disease progression was modulated either with combination anti-retroviral therapy (cART, 4 animals) or minocycline (7 animals). Twelve animals remained untreated. Viral loads were monitored in the blood and cerebral spinal fluid, as were levels of activated monocytes in the blood. Neuronal injury was monitored in vivo using magnetic resonance spectroscopy. Viral RNA was quantified in brain tissue of each animal postmortem using reverse transcription polymerase chain reaction (RT-PCR), and neuronal injury was assessed by immunohistochemistry. Without treatment, viral RNA in plasma, cerebral spinal fluid, and brain tissue appears to reach a plateau. Neuronal injury was highly correlated both to plasma viral levels and a subset of infected/activated monocytes (CD14+CD16+), which are known to traffic the virus into the brain. Treatment with either cART or minocycline decreased brain viral levels and partially reversed alterations in in vivo and immunohistochemical markers for neuronal injury. These findings suggest there is significant turnover of replicating virus within the brain and the severity of neuronal injury is directly related to the brain viral load.

Topics: Acquired Immunodeficiency Syndrome; Animals; Anti-Retroviral Agents; Disease Models, Animal; Macaca mulatta; Magnetic Resonance Imaging; Minocycline; Neurons; RNA, Viral; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus

The anticryptosporidial activity of four macrolides alone and in combination with other antimicrobial agents was investigated against ten clinical isolates of Cryptosporidium parvum recovered from stools of AIDS patients. The susceptibility tests were performed by inoculation of the protozoa on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of azithromycin, clarithromycin, roxithromycin, spiramycin, alone or in combination with artemisin, atovaquone, dapsone, minocycline or pyrimethamine. Most of the agents had an inhibitory effect on parasite growth, but only at high concentrations. No agent was able to inhibit parasite growth completely, even at the highest concentrations used. The more effective agents, azithromycin, clarithromycin, roxithromycin, minocycline and pyrimethamine, produced no more than a 13.1-27.8% reduction in oocyst count and no more than a 15.1-35.7% in schizont count. Positive interaction was clearly demonstrated when macrolides were tested in combination with minocycline or pyrimethamine.

Topics: Acquired Immunodeficiency Syndrome; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Artemisinins; Atovaquone; Cryptosporidiosis; Cryptosporidium parvum; Dapsone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Lactones; Macrolides; Minocycline; Naphthoquinones; Pyrimethamine; Sesquiterpenes

Mycobacterium haemophilum is a fastidious species that has been isolated from skin and subcutaneous nodules. The authors describe a case of Mycobacterium haemophilum osteomyelitis and skin infection in an AIDS patient and successful treatment with minocycline.

Topics: Acquired Immunodeficiency Syndrome; Adult; Diagnosis, Differential; Didanosine; Drug Therapy, Combination; Female; Humans; Minocycline; Mycobacterium Infections, Nontuberculous; Opportunistic Infections; Osteomyelitis; Tuberculosis, Osteoarticular; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adult; Brain Abscess; Ceftriaxone; Humans; Male; Minocycline; Nocardia asteroides; Nocardia Infections

A patient with the acquired immunodeficiency syndrome (AIDS) presented with Pneumocystis carinii pneumonia and pulmonary nocardiosis. The nocardial lesions appeared small and localized on chest radiograph. On two separate occasions, nocardial organisms were absent in transbronchial lung biopsy specimens, but were identified in bronchoalveolar lavage fluid probably because the latter specimen sampled a larger area of lung. The patient was initially treated with trimethoprim-sulfamethoxazole (TMP/SMX) for both infections. When TMP/SMX was discontinued because of an adverse reaction, the nocardiosis promptly exacerbated but was then easily controlled with minocycline and amikacin followed by minocycline and cycloserine. Among patients with AIDS who have sulfamethoxazole hypersensitivity during treatment for nocardiosis, alternative drugs may be efficacious and may be particularly important in this setting because they have a lower incidence of toxicity.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amikacin; Cycloserine; Drug Therapy, Combination; Humans; Male; Minocycline; Nocardia asteroides; Nocardia Infections; Pneumonia, Pneumocystis; Pulmonary Alveoli; Radiography; Respiratory Tract Infections; Therapeutic Irrigation