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1.
N Engl J Med ; 373(8): 705-13, 2015 Aug 20.
Article in English | MEDLINE | ID: mdl-26196665

ABSTRACT

BACKGROUND: Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need. METHODS: We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 virologic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events. CONCLUSIONS: Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.).


Subject(s)
Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Fluorenes/therapeutic use , HIV Infections/complications , HIV-1 , Hepacivirus , Hepatitis C, Chronic/drug therapy , Uridine Monophosphate/analogs & derivatives , Anti-Retroviral Agents/therapeutic use , Antiviral Agents/adverse effects , Benzimidazoles/adverse effects , Benzimidazoles/pharmacokinetics , Drug Resistance, Viral , Drug Therapy, Combination , Female , Fluorenes/adverse effects , Fluorenes/pharmacokinetics , Genotype , HIV Infections/drug therapy , Hepacivirus/drug effects , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C, Chronic/complications , Humans , Male , Middle Aged , RNA, Viral/blood , Sofosbuvir , Uridine Monophosphate/adverse effects , Uridine Monophosphate/pharmacokinetics , Uridine Monophosphate/therapeutic use , Viral Load
3.
Inflamm Bowel Dis ; 18(12): 2392-403, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22434654

ABSTRACT

BACKGROUND: The risk of viral infection is increased in immunosuppressed inflammatory bowel disease (IBD) patients. Varicella zoster virus (VZV) is of particular interest in IBD because of a number of reports of severe, disseminated, and occasionally fatal varicella infection in immunosuppressed IBD patients. METHODS: We reviewed publications describing VZV infection in IBD patients and combined these data with a review of the current literature relating to both primary and secondary varicella in IBD. RESULTS: Twenty cases of primary varicella infection and 32 cases of herpes zoster infection have been reported in IBD. Additional cases are reported in clinical trials. The risk of VZV infection is increased with all immunosuppressants used in IBD, but corticosteroids and combination immunosuppression appear to be a particular risk. CONCLUSIONS: Healthcare providers need to be aware of the various manifestations of primary and secondary VZV infection in immunosuppressed IBD patients. Patients should be screened for VZV immunity and vaccinated prior to commencing immunosuppression.


Subject(s)
Chickenpox/etiology , Inflammatory Bowel Diseases/complications , Adolescent , Adult , Chickenpox/virology , Child , Female , Herpes Zoster/etiology , Herpes Zoster/virology , Herpesvirus 3, Human , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/virology , Male , Risk Factors , Young Adult
4.
AIDS Patient Care STDS ; 26(1): 36-52, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22070609

ABSTRACT

Men who have sex with men (MSM) have the highest incidence of HIV infection in the United States. One of the contributing factors to HIV spread among this group is the use of crystal methamphetamine ("meth"). The objective was to review the behavioral impact of crystal meth use in HIV-infected MSM and potential treatment options. A systematic review of MEDLINE identified studies that evaluated the clinical effects of crystal meth on the HIV-infected MSM population. Search terms included HIV, methamphetamine, MSM, antiretroviral therapy, adherence, resistance, and treatment. U.S. citations in the English language in peer-reviewed journals until December 2010 were included. The primary author reviewed eligible articles, and relevant data including study design, sample, and outcomes were entered into an electronic data table. The 61 included studies highlight that HIV-infected MSM who use crystal meth are more likely to report high-risk sexual behaviors, incident sexually transmitted infections, and serodiscordant unprotected anal intercourse, compared to HIV-infected MSM who do not use crystal meth. Medication adherence in this population is notably low, which may contribute to transmission of resistant virus. No medications have proven effective in the treatment of crystal meth addiction, and the role of behavioral therapies, such as contingency management are still in question. HIV-infected MSM who abuse crystal meth have worse HIV-related health outcomes. Behavioral interventions have shown variable results in treating crystal meth addiction, and more investigation into rehabilitation options are needed. The results presented support efforts to develop and implement novel interventions to reduce crystal meth use in HIV-infected MSM.


Subject(s)
Central Nervous System Stimulants/adverse effects , HIV Seropositivity/epidemiology , Homosexuality, Male , Methamphetamine/adverse effects , Substance-Related Disorders/epidemiology , Unsafe Sex/statistics & numerical data , Adult , HIV Seropositivity/drug therapy , HIV Seropositivity/transmission , Humans , Male , Population Surveillance , Risk Factors , Risk-Taking , Surveys and Questionnaires , Treatment Outcome , United States/epidemiology , Unsafe Sex/prevention & control
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