minocycline and HIV-Infections

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

We conducted a study of minocycline to assess its safety, tolerability, and efficacy for the treatment of HIV-associated cognitive impairment.. HIV-1-infected individuals with progressive neurocognitive decline were enrolled in a double-blind, placebo-controlled study of minocycline. Participants were randomized to receive minocycline 100 mg or matching placebo orally every 12 hours. The primary efficacy measure was change in a neuropsychological test composite z score (NPZ-8) from baseline to week 24. Measures of safety included the frequency of adverse events and changes over time in laboratory tests. After 50% of participants completed the double-blind phase, an interim analysis of futility for the primary outcome measure was performed, and our Data and Safety Monitoring Board recommended early study termination.. A total of 107 HIV-1-infected individuals with cognitive impairment were enrolled. The minocycline group did not show improvement in the primary outcome measure (NPZ-8) (mean 24-week change = 0.12) compared to placebo (mean 24-week change = 0.17) (95% confidence interval = [-0.26, 0.39], p = 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group.. Minocycline was safe and well-tolerated in individuals with HIV-associated cognitive impairment, but cognitive improvement was not observed. Classification of evidence. This interventional study provides Class II evidence for the safety, tolerability, and efficacy of minocycline for the treatment of HIV-associated cognitive impairment.

Topics: Adult; Cognition Disorders; Cohort Studies; Double-Blind Method; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Male; Middle Aged; Minocycline; Treatment Outcome

Sexually transmitted infection (STI) rates in the U.S. have rapidly increased in the past decade. Although most of this rise is due to syphilis, gonorrhea, and chlamydia, less common STIs are also rising, including Mycoplasma genitalium. We present the case of a 40-year-old male with a history of virologically-suppressed human immunodeficiency virus (HIV) infection who presented with recurrent nongonococcal urethritis. Unfortunately, his symptoms were refractory to multiple empiric drug regimens, and he was eventually diagnosed with Mycoplasma genitalium. After consultation with the Centers for Disease Control and Prevention STI branch, minocycline was successfully used to eradicate the infection.

Topics: Adult; HIV Infections; Humans; Male; Minocycline; Mycoplasma genitalium; Mycoplasma Infections; United States; Urethritis

Cryptococcus neoformans infections occur in immunocompromised patients, especially those with HIV infection, chemoradiotherapy after cancer, and organ transplantation. Infection can cause pneumonia and meningoencephalitis in severe cases with a high mortality rate if not treated. Although fluconazole and amphotericin B are the first-line treatments for cryptococcosis, the rate of fluconazole resistance has increased significantly due to long-term use. Minocycline is a derivative of tetracycline that exerts its antibacterial effect through inhibition of bacterial protein synthesis. It is also able to pass the blood-brain barrier to act on the central nervous system. The present study investigates the effects of minocycline in combination with antifungals in treating C. neoformans.. To determine in vitro interactions of minocycline combined with itraconazole, voriconazole, posaconazole, fluconazole and amphotericin B against C. neoformans.. The minimum inhibitory concentrations (MIC) of the antifungals were determined by the CLSI Clinical and Laboratory Standards Institute M27-A3 microdilution method. The in vitro synergistic effects of minocycline combined with itraconazole, voriconazole, posaconazole, fluconazole, and amphotericin B on C. neoformans were detected by the broth microdilution checkerboard technique and disk diffusion testing.. The working concentration ranges were 0.125-4 µg/mL for itraconazole, 0.03-0.125 µg/ml for voriconazole, 0.03-1 µg/ml for posaconazole, 0.25-16 µg/ml for fluconazole, and 0.125-2 µg/ml for amphotericin B. The synergistic rates of minocycline combinations against C. neoformans were 55% with itraconazole, 10% with voriconazole, 85% with posaconazole, 20% with fluconazole, and 70% with amphotericin B. The effective MIC value of minocycline in the synergistic combination decreased to 2-32 µg/ml, while the MIC of itraconazole decreased to 0.03-0.125 µg/ml, voriconazole 0.03-0.125 µg/ml, posaconazole 0.03-0.125 µg/ml, 0.125-4 µg/ml fluconazole, and 0.06-0.50 µg/ml amphotericin B. The disk diffusion assay showed that the plates containing minocycline and antifungal drugs produced inhibition zones with diameters larger than the single drug plates. Minocycline showed no antagonistic effect in the combinations. In conclusion, the combination of minocycline and azoles or amphotericin B has synergistic effects against C. neoformans in vitro.

Topics: Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Fluconazole; HIV Infections; Humans; Microbial Sensitivity Tests; Minocycline

Topics: Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; HIV Infections; Homosexuality, Male; Humans; Japan; Male; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Scrotum; Staphylococcal Infections; Treatment Outcome; Ulcer

More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T-cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB-HPCs) -transplanted humanized NOD/LtsZ-scidIL-2Rγ(null) mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up-regulation of several T-cell immune activation markers such as CD38, HLA-DR, CD69 and co-receptor CCR5. T-cell exhaustion markers PD-1 and CTLA-4 were found to be significantly up-regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin-10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T-cell counts in HIV-infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low-cost adjunctive treatment to regulate chronic immune activation and replication of HIV.

Topics: Animals; Anti-Bacterial Agents; HIV Infections; HIV-1; Humans; Interleukin-10; Mice; Mice, Inbred NOD; Mice, SCID; Minocycline; Virus Replication

HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic innate immune responses that drive T cell activation and apoptosis and 2) induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3) but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo.

Topics: Animals; Anti-Retroviral Agents; CD4-Positive T-Lymphocytes; Cell Separation; CTLA-4 Antigen; Dendritic Cells; Drug Therapy, Combination; Flow Cytometry; Gene Expression Regulation; HIV Infections; HIV-1; Humans; Immunity; Indoleamine-Pyrrole 2,3,-Dioxygenase; Influenza, Human; Interferon Type I; Lymphocyte Activation; Macaca nemestrina; Minocycline; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Tetracycline; TNF-Related Apoptosis-Inducing Ligand

An effective anti-human immunodeficiency virus-1 (HIV-1) microbicide should exert its action in the absence of causing aberrant activation of topical immunity that will increase the risk of HIV acquisition. In the present study, we demonstrated that the vaginal application of cellulose sulfate (CS) gel induced topical mucosal inflammatory responses; the addition of minocycline to CS gel could significantly attenuate the inflammation in a mice model. The combined gel of CS plus minocycline not only reduced the production of inflammatory cytokines in cervicovaginal lavages (CVLs), also down-regulated the activation of CD4+ T cells and the recruitment of other immune cells including HIV target cells into vaginal tissues. Furthermore, an In vitro HIV-1 pseudovirus infection inhibition assay showed that the combined gel decreased the infection efficacy of different subtypes of HIV-1 pseudoviruses compared with that of CS gel alone. These results implicate that minocycline could be integrated into microbicide formulation to suppress the aberrant activation of topical mucosal immunity and enhance the safety profile during the application of microbicides.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; CD4-Positive T-Lymphocytes; Cellulose; Down-Regulation; Drug Evaluation, Preclinical; Female; Gels; HIV Infections; Inflammation; Mice; Mice, Inbred BALB C; Minocycline; Mucous Membrane; Vagina

Malignant syphilis is now considered a rare disease, more commonly affecting individuals with poor health, malnutrition or HIV infection. We present a 34-year-old man with HIV infection who developed multiple atypical cutaneous ulcerations, leonine facies, a scleral nodule and keratitis with visual loss. The diagnosis of malignant syphilis was delayed due to the insidious presentation, but was confirmed via immunohistochemical (IHC) staining with anti-Treponema antibodies of a skin biopsy. Significant clinical improvement was observed following a 15-day course of penicillin and tigecycline therapy. In advanced HIV disease, cutaneous manifestations are often difficult to identify and present a challenge for the clinician. Clinical manifestations of secondary syphilis vary greatly, earning the epigram of 'the great imitator'. It is important to recognize atypical presentations of syphilis, especially among HIV-infected individuals. Unlike historical cases of malignant syphilis, Treponema pallidum was found in the tissue section using IHC staining methods. We emphasize the importance of lues maligna in the differential diagnosis of HIV-infected patients with diffuse ulceronodular lesions as well as the usefulness of histological investigations and IHC studies.

Topics: Adult; Anti-Bacterial Agents; Biopsy; Eye Diseases; HIV Infections; Humans; Immunohistochemistry; Male; Minocycline; Penicillins; Syphilis; Tigecycline; Treatment Outcome; Treponema pallidum

Topics: Animals; Anti-HIV Agents; Chemotherapy, Adjuvant; Cytokines; HIV Infections; Humans; Minocycline

Treatment of human immunodeficiency virus (HIV) infection with highly active antiretroviral therapy (HAART) is effective but can be associated with toxic effects and is expensive. Other options may be useful for long-term therapy. The immunomodulatory antibiotic minocycline could be an effective, low-cost adjunctive treatment to HAART. Minocycline mediated a dose-dependent decrease in single-cycle CXCR4-tropic HIV infection and decreased viral RNA after infection of CD4+ T cells with HIV NL4-3. Reactivation from latency was also decreased in a primary CD4+ T cell-derived model and in resting CD4+ T cells from HIV-infected patients. Minocycline treatment resulted in significant changes in activation marker expression and inhibited proliferation and cytokine secretion of CD4+ T cells in response to activation. This study demonstrates that minocycline reduces HIV replication and reactivation and decreases CD4+ T cell activation. The anti-HIV effects of minocycline are mediated by altering the cellular environment rather than directly targeting virus, placing minocycline in the class of anticellular anti-HIV drugs.

Topics: Anti-HIV Agents; CD4-Positive T-Lymphocytes; Cell Transformation, Viral; Cells, Cultured; Cytokines; DNA, Viral; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; HIV; HIV Infections; Humans; Lymphocyte Activation; Minocycline; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Viremia; Virus Latency

Topics: Antiretroviral Therapy, Highly Active; Drug Resistance, Viral; Drug Therapy, Combination; HIV Infections; Humans; Minocycline

Topics: Case-Control Studies; CD4-Positive T-Lymphocytes; Dose-Response Relationship, Drug; HIV Infections; Humans; Lymphocyte Activation; Minocycline

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Eosinophilia; Female; Folliculitis; Histamine Antagonists; HIV Infections; Humans; Minocycline; Mucinosis, Follicular

HIV-infected patients with opportunistic infections receive therapeutic regimens that often contain numerous drugs and are then exposed to potential drug-to-drug interactions. We report here an unusual case of relapse of toxoplasmic encephalitis in an HIV-infected patient, possibly due to a drug-to-drug interaction between dapsone and minocycline.

Topics: Adult; Dapsone; Drug Interactions; Encephalitis; HIV Infections; HIV-1; Humans; Male; Minocycline; Recurrence; Toxoplasma; Toxoplasmosis, Cerebral

Minocycline and valproic acid are potential adjuvant therapies for the treatment of human immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this study was to determine whether minocycline alone or in combination with valproic acid affected atazanavir plasma concentrations. Twelve adult HIV-infected subjects whose regimen included atazanavir (300 mg)-ritonavir (100 mg) daily for at least 4 weeks were enrolled. Each subject received atazanavir-ritonavir on day 1, atazanavir-ritonavir plus 100 mg minocycline twice daily on days 2 to 15, and atazanavir-ritonavir plus 100 mg minocycline twice daily and 250 mg valproic acid twice daily on days 16 to 30 with meals. The subjects had 11 plasma samples drawn over a dosing interval on days 1, 15, and 30. The coadministration of minocycline and valproic acid with atazanavir-ritonavir was well tolerated in all 12 subjects (six male; mean [+/- standard deviation] age was 43.1 [8.2] years). The geometric mean ratios (GMRs; 95% confidence interval [CI]) for the atazanavir area under the concentration-time curve from 0 to 24 h at steady state (AUC(0-24)), the plasma concentration 24 h after the dose (C(min)), and the maximum concentration during the dosing interval (C(max)) with and without minocycline were 0.67 (0.50 to 0.90), 0.50 (0.28 to 0.89), and 0.75 (0.58 to 0.95), respectively. Similar decreases in atazanavir exposure were seen after the addition of valproic acid. The GMRs (95% CI) for atazanavir AUC(0-24), C(min), and C(max) with and without minocycline plus valproic acid were 0.68 (0.43 to 1.06), 0.50 (0.24 to 1.06), and 0.66 (0.41 to 1.06), respectively. Coadministration of neither minocycline nor minocycline plus valproic acid appeared to influence the plasma concentrations of ritonavir (P > 0.2). Minocycline coadministration resulted in decreased atazanavir exposure, and there was no evidence that the addition of valproic acid mediated this effect.

Topics: Adult; Anticonvulsants; Atazanavir Sulfate; Cognition Disorders; Drug Interactions; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Male; Middle Aged; Minocycline; Oligopeptides; Pyridines; Ritonavir; Valproic Acid

The WHO MDT regimens have proved highly successful in preventing relapse of leprosy cases. It has indirectly lad to marked reduction in prevalence of disabilities. For PB leprosy, rifampicin 600 mg monthly and 100 mg dapsone daily for a total of 6 months therapy is required. For MB leprosy clofazimine 300 mg once monthly, supervised and 50 mg daily self administered is added. For single skin lesion the current WHO recommendation is 600 mg rifampicin + 400 mg ofloxacin + 100 mg minocycline given as a single dose for adults. Dose adjustment for children and clinical information have been discussed in a nutshell. A number of trials are going on, some are yet to be completed which do offer the prospect of perhaps simplifying therapy and improving with shorter duration.

Topics: Anti-Bacterial Agents; Clofazimine; Dapsone; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; HIV Infections; Humans; Hypersensitivity; India; Leprosy; Minocycline; Nausea; Ofloxacin; Rifampin; Secondary Prevention; Tuberculosis; World Health Organization

The presence of Ureaplasma urealyticum was evaluated on 1912 vaginal and urethral swabs from HIV-1 seronegative (HIV-) inpatients (210) and outpatients (503) suffering from acute urethritis or vaginitis; asymptomatic HIV- outpatients (201); and asymptomatic HIV-1 seropositive (HIV+) inpatients (120). The study reported an increased frequency of Ureaplasma urealyticum isolates in asymptomatic HIV+ compared to asymptomatic HIV- subjects. As expected, the frequency of Ureaplasma urealyticum isolates increased in symptomatic HIV- subjects. Strains of Ureaplasma urealyticum resistant to ciprofloxacin, tetracycline and minocycline were more frequently isolated in HIV+ (34.1%) than HIV- (3.8%) subjects; on the other hand, only 1 out of 704 (0.1%) strains isolated from outpatients was resistant to ciprofloxacin. We found no association in HIV+ patients between Ureaplasma urealyticum infection and CD4 count or HIV-1 p24 antigenemia.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Microbial; Female; HIV Infections; HIV-1; Humans; Male; Minocycline; Tetracycline; Ureaplasma urealyticum; Urethra; Vagina