determining responses to two different vaccines in hiv and hcv infected individuals

Conditions: HIV Infections; Hepatitis C

Summary: infection with either hiv or hepatitis c virus (hcv) affects immune system responses. the purpose of this study is to investigate the immune responses to two different vaccine formulations in hiv-infected, hcv-infected, and hcv/hiv- coinfected individuals.

individuals with hcv and hiv coinfection are especially hard to treat, and as a result, account for a high rate of deaths each year. because hcv and hiv share transmission routes, hcv/hiv coinfection is common. liver disease has emerged as a significant cause of death in individuals coinfected with hcv and hiv. currently, the mechanisms by which hcv and hiv interact in hcv/hiv-coinfected individuals, including how these infections affect immune responses, are poorly understood. research suggests that vaccination may prevent other comorbidities associated with hcv/hiv coinfection; however, responses to new vaccine antigens have been shown to be impaired in hcv or hiv-infected individuals. the purpose of this study is to identify the innate and adaptive immune defects present in hcv-infected, hiv-infected, and hcv/hiv-coinfected individuals. this study will evaluate whether these innate and adaptive immune defects predict responses to hbv neoantigen in the form of both a diphtheria/tetanus toxoid immunization (decavac)and a hepatitis a-hepatitis b immunization (twinrix). this study will last approximately 24 weeks. participants will be stratified to one of three arms, based on their hcv and hiv status: * arm a will enroll hcv-infected individuals who are hiv-uninfected * arm b will enroll hiv-infected individuals who are hcv-uninfected * arm c will enroll hcv/hiv-coinfected individuals arms b and c will open for enrollment before arm a. opening of enrollment for arm a will be determined by the accrual progress of arms b and c as evaluated by the actg scientific agenda steering committee. all participants will receive decavac vaccination on day 0, and a twinrix vaccination on days 0, 7, and 21. study visits will occur around days 0, 7, and 21, and at weeks 6, 8, 12, and 24; all visits will include medical and medication history, blood collection, and a physical exam. medication to treat hcv or hiv will not be provided by the study.

Eligibility criteria:
inclusion criteria for arm a participants: * hcv-infected * hiv-uninfected inclusion criteria for arm b participants: * hiv-infected * hcv-uninfected * cd4 count greater than or equal to 300 cells/mm3 within 60 days prior to study entry inclusion criteria for arm c participants: * hiv-infected * hcv-infected inclusion criteria for all participants: * documented hepatitis b virus (hbv) antibody status. if anti-hbv core antibody positive, documented hbv negative test within 30 days prior to study entry is required. * willing to use acceptable forms of contraception for the duration of the study and for 24 weeks after the last vaccination exclusion criteria for arm a participants: * concurrent or recent treatment for hcv infection (within the past three months) exclusion criteria for arm b participants: * current, prior, or clinical need for antiretroviral therapy (within the past three months prior to study entry) * opportunistic infection other than hcv exclusion criteria for arm c participants: * concurrent or recent treatment for hcv infection (within the past three months) * current, prior, or clinical need for antiretroviral therapy (within the past three months prior to study entry). more information on this criterion can be found in the protocol. * opportunistic infection other than hcv exclusion criteria for all participants: * history of exposure to hepatitis a vaccine, hepatitis b vaccine, or combined hepatitis a-hepatitis b vaccines * immunomodulatory agents for 7 days or more within 30 days prior to study entry. more information on this criterion can be found in the protocol. * concurrent immunizations (e.g., influenza, pneumococcal, other vaccine)within 3 days prior to study entry * active or recent (in the last six months prior to study entry) cdc category c event. more information on this criterion can be found in the protocol * systemic anticancer chemotherapy or radiation within 24 weeks prior to study entry, or anticipated need to begin such treatment * past or current immunologically-mediated disease. more information on this criterion can be found in the protocol. * current bacterial infection requiring treatment, therapy, or hospitalization within 1 week prior to study entry * serious illness requiring systemic treatment and/or hospitalization. participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded. * current uncontrolled seizure disorders * active bleeding varices, or child's b or c cirrhosis. more information on this criterion can be found in the protocol. * serious bleeding disorder that poses a risk to a participant for intramuscular injections * known allergy or sensitivity to study vaccines or their formulations * current drug or alcohol use that, in the opinion of the investigator, interferes with study participation * pregnant or breastfeeding * use of systemic investigational agents within 30 days prior to entry * history of any hepatitis a vaccine within one year

Keywords: treatment experienced treatment naive immunizations