The current pandemic of sexually transmitted human immunodeficiency virus (HIV) infection--the causative agent of acquired immunodeficiency syndrome (AIDS), has created an urgent need for a new type of contraceptive: one that is both a spermicide and a microbicide. Because most women at risk for HIV infection are of reproductive age (15-44 years), effective use of dual-function contraceptives is important to prevent HIV transmission and unintended pregnancies. In the absence of an effective prophylactic anti-HIV therapy or vaccine, new emphasis has been placed on the development of intravaginal microbicidal agents capable of reducing the transmission of HIV. Topical microbicidal spermicides would ideally provide a female-controlled method of self-protection against HIV as well as preventing pregnancy. However, several microbicides that are undergoing preclinical and human clinical trials contain detergent-type ingredients. The detergent-type spermicide, nonoxynol-9, the only recommended microbicide for protection against sexual transmission of HIV has been shown to cause lesions in vaginal and cervical epithelia leaving women more vulnerable to HIV infection. Therefore, a major challenge in microbicide research has been to design mechanism-based microbicides that are highly effective against pregnancy and HIV transmission while lacking detergent-type effects on epithelial cells and normal vaginal flora. We present an overview of current microbicide research and report on the identification and preclinical development of novel non-detergent spermicidal nucleoside and non-nucleoside inhibitors aimed at decreasing pregnancy and preventing sexual transmission of HIV.
IntroductionAfter the results of phase III vaccine studies became available, the leading oncology societies recommended two doses of COVID-19 vaccination to all patients with cancer with no specific recommendation for tumor type and active treatments. However, the data on the COVID-19 vaccine efficacy in cancer patients is limited due to exclusion of cancer patients from most vaccine clinical trials. Therefore, we systemically reviewed the available evidence evaluating the antibody responses in cancer patients.MethodsWe conducted a systematic search from the Pubmed database and calculated risk differences (RD) and 95% confidence intervals (CI) to compare seroconversion rates between cancer patients and controls using the Review Manager software, version 5.3.ResultsOur systematic search retrieved a total 27 studies and we included 17 studies with control arms in the analyses. Cancer patients had significantly lower seroconversion rates (37.3%) than controls (74.1%) (RD: -0.44, 95% CI: -0.52, -0.35, p<0.001) with first vaccine dose. After two doses, the seroconversion rates were 99.6% in control arm and 78.3% in cancer patients (RD: -0.19, 95% CI: -0.28, -0.10, p<0.001). The difference in seroconversion rates was more pronounced patients with hematologic malignancies (72.6%) (RD: -0.25, 95% CI: -0.27, -0.22, p<0.001) than patients with solid tumors (91.6%) (RD: -0.09, 95% CI: -0.13, -0.04, p<0.003) and patients in remission (RD: -0.10, 95% CI: -0.14, -0.06, p<0.001).ConclusionIn conclusion, COVID-19 vaccine seroconversion rates were significantly lower in patients with hematological malignancies and patients under active treatment. Further research focusing on the approaches to improve vaccine efficacy and exploration of novel treatment options is urgently needed for these patients.
The findings of the current study confirm that Ph chromosome positivity represents a significant independent adverse risk factor for childhood ALL that has not been abrogated by current intensive chemotherapy programs. BMT at the time of first remission, as well as other alternative strategies employing biotherapeutic agents, should be considered in future front-line trials for pediatric patients with Ph+ ALL.
We have evaluated the clinical potential of TXU (anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate (TXU-PAP) as a new biotherapeutic anti-human immunodeficiency virus (anti-HIV) agent by evaluating its anti-HIV type 1 (anti-HIV-1) activity in vitro, as well as in a surrogate human peripheral blood lymphocyte-severe combined immunodeficient (Hu-PBL-SCID) mouse model of human AIDS. The present report documents in a side-by-side comparison the superior in vitro anti-HIV-1 activity of TXU-PAP compared to the activities of zidovudine, 2′,3′-didehydro-2′,3′-dideoxythymidine, unconjugated PAP, and B53-PAP, an anti-CD4-PAP immunoconjugate. Notably, TXU-PAP elicited potent anti-HIV activity in the Hu-PBL-SCID mouse model of human AIDS without any side effects and at doses that were very well tolerated by cynomolgus monkeys. Furthermore, plasma samples from TXU-PAP-treated cynomolgus monkeys showed potent anti-HIV-1 activity in vitro.
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