alitretinoin and AIDS-Related-Opportunistic-Infections

Treatment guidelines are not well established in AIDS-related Kaposi sarcoma (KS).. We aim to review the evidence on efficacy of treatments for AIDS-related Kaposi sarcoma.. We searched the Cochrane Library, PubMed, and Embase Database from date of database inception till July 2020. Randomized controlled trials reporting intervention consisting of any type of treatment compared to control/placebo to a different treatment modality or different combination of treatment/treatment doses with a diagnosis of AIDS-related KS are selected.. Primary outcomes were response rates defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Secondary outcomes were cosmesis and adverse outcomes such as pain and erythema.. Thirteen out of 536 articles met our eligibility criteria. Three studies reported the efficacy of chemotherapy, two studies looked at different doses of radiotherapy regimes, and three studies compared different antiretroviral therapy (ART) and chemotherapy regimens. Other studies reported topical therapies such as alitretinoin gel, IM862, and bHCG injection which showed varied efficacies.. Lack of standardization classification of disease activity and clinical outcomes and treatment modalities precluded meaningful comparison of studies.. The evidence of efficacy of any particular intervention is overall varied and there was insufficient evidence to recommend any particular intervention. We have provided an overview of treatments for KS but larger studies need to be carried out to verify the efficacy of treatment options reported in the literature.

Topics: AIDS-Related Opportunistic Infections; Alitretinoin; Antineoplastic Agents; HIV Infections; Humans; Sarcoma, Kaposi

To evaluate the efficacy and safety of topical alitretinoin gel (9-cis-retinoic acid [LGD1057], Panretin gel; Ligand Pharmaceuticals, Inc, San Diego, Calif) in cutaneous Kaposi sarcoma (KS).. Open-label, within-patient, controlled, dose-escalating phase 1 and 2 clinical trials. In all patients, 1 or more cutaneous KS lesions were treated with alitretinoin gel, and at least 2 other lesions served as untreated controls for up to 16 weeks. Alitretinoin (0.05% or 0.1% gel) was applied twice daily for the first 2 weeks and up to 4 times daily thereafter, if tolerated.. Nine academic clinical centers.. One hundred fifteen patients with biopsy-proven acquired immunodeficiency syndrome (AIDS)-related KS.. AIDS Clinical Trials Group response criteria.. Statistically significant clinical responses were observed in 31 (27%) of 115 patients for the group of treated index lesions compared with 13 (11%) for the group of untreated control lesions (P<.001). Responses occurred with low CD4(+) lymphocyte counts (<200 cells/microL) and in some patients with refractory response to previous systemic anti-KS therapy. The incidence of disease progression was significantly lower for treated index lesions compared with untreated control lesions (39/115 [34%] vs 53/115 [46%]; P =.02). Alitretinoin gel generally was well tolerated, with 90% of treatment-related adverse events confined to the application site and only mild or moderate in severity.. Alitretinoin gel has significant antitumor activity as a topical treatment for AIDS-related KS lesions, substantially reduces the incidence of disease progression in treated lesions, and is generally well tolerated.

Topics: Administration, Cutaneous; Adult; AIDS-Related Opportunistic Infections; Alitretinoin; Antineoplastic Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Gels; Humans; Male; Middle Aged; Sarcoma, Kaposi; Skin Neoplasms; Treatment Outcome; Tretinoin; United States

Kaposi's sarcoma (KS) is the most frequent malignancy in patients with HIV. Given the promise that retinoids show in the treatment of various hyperproliferative skin disorders and in vitro evidence of inhibition of proliferation of KS cells, a randomized, controlled clinical trial was conducted.. A 12-week, multicenter, randomized, double-blind, vehicle-controlled safety and efficacy evaluation of topical alitretinoin 0.1% gel applied to cutaneous KS lesions was conducted in HIV-infected patients. The primary efficacy endpoint was the patient's response rate, as determined by evaluating six index lesions representative of the patient's overall KS cutaneous disease using AIDS Clinical Trials Group (ACTG) response criteria applied to topical therapy. Of 268 patients entered in the blinded treatment phase of the study (alitretinoin group, n = 134; vehicle group, n = 134), 47 patients (35%) treated with alitretinoin 0.1% gel had a positive response, compared with 24 patients (18%) treated with vehicle gel. Of 184 patients receiving open-label alitretinoin treatment following the blinded phase of the trial, 90 patients (49%) met criteria for a positive response. This superior efficacy of alitretinoin gel over vehicle gel was maintained when the data were adjusted or analyzed for age, race, Kamofsky scores, baseline CD4+ lymphocyte counts, number of raised lesions at baseline, and aggregate area of index lesions. Alitretinoin 0.1% gel was superior to vehicle gel regardless of the number of concurrent antiretroviral therapies. Most adverse events were mild to moderate in severity, limited to the application site, and reversible on reduction in frequency or suspension of application. Relatively few patients (7%) discontinued alitretinoin therapy because of to related adverse events.. The results show that alitretinoin gel application is safe and generally well tolerated, and they indicate the superiority of alitretinoin 0.1% gel over vehicle gel in the treatment of cutaneous AIDS-related KS lesions.

Topics: Administration, Topical; Adult; Aged; AIDS-Related Opportunistic Infections; Alitretinoin; Anti-HIV Agents; Antineoplastic Agents; Double-Blind Method; Drug Therapy, Combination; Female; Gels; Humans; Male; Middle Aged; Sarcoma, Kaposi; Tretinoin

Human immunodeficiency virus (HIV) causes disease by infecting lymphocytes and progressively destroying critical regulatory and effector cells of the immune system, leaving patients vulnerable to a number of bacterial, fungal, and viral infections. Facial herpes (herpes simplex virus-1 [HSV-1]), genital herpes (HSV-2), herpes zoster (varicella zoster virus), oral hairy leukoplakia (Epstein-Barr virus), Kaposi's sarcoma (HHV-8), molluscum contagiosum, condyloma acuminata (human papillomavirus [HPV-6, HPV-11]), plantar warts (HPV-1), and facial warts and flat warts (HPV-5) are some of the cutaneous viral diseases most commonly seen in HIV-infected patients. Two immunomodulatory agents, imiquimod (Aldara), shown to be safe and effective in the management of genital warts, and alitretinoin gel, shown to be safe and effective in the treatment of Kaposi's sarcoma, may offer a new therapeutic approach to treatment of cutaneous viral diseases. There is a strong scientific rationale to suggest that imiquimod and alitretinoin gel may be useful in the treatment of a variety of cutaneous viral diseases that have been shown to respond to immunomodulatory drugs. This represents a new approach in the therapeutic treatment paradigm for treatment of cutaneous viral diseases at their site of infection.

Topics: Adjuvants, Immunologic; AIDS-Related Opportunistic Infections; Alitretinoin; Aminoquinolines; Antiviral Agents; Condylomata Acuminata; Gels; Humans; Imiquimod; Molluscum Contagiosum; Skin Diseases, Viral; Tretinoin

Topics: Administration, Cutaneous; AIDS-Related Opportunistic Infections; Alitretinoin; Anti-HIV Agents; Dermatologic Agents; Drug Administration Schedule; Humans; Sarcoma, Kaposi; Skin Neoplasms; Treatment Outcome; Tretinoin

Topics: Administration, Topical; AIDS-Related Opportunistic Infections; Alitretinoin; Antineoplastic Agents; Clinical Trials as Topic; Drug Approval; Gels; Humans; Sarcoma, Kaposi; Tretinoin; United States; United States Food and Drug Administration