Systematic review of the efficacy and safety of biological therapy for inflammatory conditions in HIV-infected individuals

Abstract

Biologic therapies are injectable immunomodulatory agents directed against specific immune cell or chemical targets. They have transformed the lives of HIV-uninfected individuals with severe inflammatory conditions including psoriasis, rheumatoid arthritis, and ulcerative colitis. The perceived increased infection risk associated with these agents means that HIV-infected individuals have not been included in randomised control trials of these drugs. The literature for use of biologic therapies in HIV-infected populations is limited to case reports and case series. There are additional data on use of rituximab, a monoclonal antibody against B lymphocytes, in the setting of HIV-associated haematological malignancy. We performed a systematic review of efficacy and safety of biologic therapy for inflammatory conditions in HIV-infected individuals. Our systematic review identified 37 treatment episodes with six different biologic agents encompassing 10 different inflammatory conditions. Broadly, efficacy of the agents studied was comparable to reports from HIV-uninfected patients. Both infectious and non-infectious sequelae were also comparable with trial data from HIV-uninfected patients. HIV control, even for the minority of individuals not receiving anti-retroviral therapy (ART) at the time of biologic therapy, was not adversely affected. However, detail was limited concerning ART regimens and both immunological and virological parameters of follow-up. Overall available literature is of very low quality and likely subject to publication bias of successful cases. Firm conclusions are not possible regarding the efficacy and safety of biologic agents in HIV-infected individuals; however, there appear to be sufficient data to warrant inclusion of individuals with well-controlled HIV in future trial studies.

HIV‐associated psoriasis: Epidemiology, pathogenesis, and management

“…Data available in literature highlights that treatment responses in PLWH are comparable to those observed in HIV‐negative patients affected by psoriasis (Fink et al, ). Moreover, there are no negative effects on ART (Fink et al, ).…”

“…Data available in literature highlights that treatment responses in PLWH are comparable to those observed in HIV-negative patients affected by psoriasis (Fink et al, 2017). Moreover, there are no negative effects on ART (Fink et al, 2017). However, even though Cepeda et al (2008) suggested that anti-TNFα treatments are effective and well tolerated in PLWH with a CD4+ T-lymphocyte count >200/mm 3 , there are only limited efficacy and safety data, and some authors suggest limiting the use of anti-TNFα agents to those unresponsive to standard therapeutic regimens (Bartke et al, 2004;Cepeda et al, 2008;Cobo Ibáñez et al, 2009;De Simone et al, 2016;Di Lernia et al, 2013;Gaylis, 2003;Kaur et al, 2007;Linardaki et al, 2007;Mikhail et al, 2008;Paparizos et al, 2012;Reddy et al, 2017;Sellam et al, 2007;Sha et al, 2002;Wallis et al, 2004).…”

“…This class of biologic drugs includes monoclonal antibodies and enzyme inhibitors with multiple therapeutic mechanisms, such as targeting TNFα directly or neutralizing soluble receptor antagonists (Fink et al, 2017;Rustin, 2012). Seeing that TNFα is a pro-inflammatory cytokine, the ultimate effect of these drugs is reduction of the inflammation, but they also impair appropriate immune responses to infections (Fink et al, 2017;Rustin, 2012). Di Lernia et al, 2013;Gaylis, 2003;Kaur, Chan, & Berney, 2007;Linardaki, Katsarou, Ioannidou, Karafoulidou, & Boki, 2007;Mikhail, Weinberg, & Smith, 2008;Paparizos et al, 2012;Reddy et al, 2017;Sellam et al, 2007;Sha et al, 2002;Wallis et al, 2004).…”

Human immunodeficiency virus infection (HIV)–associated rheumatic manifestations in thepre- and post-HAART eras

“…At present, biologic agents and other DMARDs (including glucocorticoids, hydroxychloroquine, sulfasalazine, methotrexate, leflunomide, mofetil mycophenolate, azathioprine, cyclophosphamide, cyclosporine) are recommended when patients have CD4+ T cell counts above 200 cells/mm 3 and HIV viral activity completely suppressed [62][63][64]. In addition, they have been shown to be effective, safe, and well-tolerated.…”

Effects of Biologic Therapies for Cutaneous Inflammatory Diseases in HIV-Infected Individuals: Reliable or Not?

“…Biologic agents targeting specific molecular pathways in the immune system play an important therapeutic role for management of patients with severe or refractory dermatologic diseases (1). The most of biologic therapies used for inflammatory conditions target 'tumour necrosis factor-alpha (TNF-α)' , which is very important in host defense against intracellular pathogens (2,3). The biologic agents are commonly used for the management of psoriasis and psoriatic arthritis in dermatology patients (4).…”