Antiretroviral agents against human immunodeficiency virus: an overview of current drugs and new perspectives / Agentes antiretrovirais contra o vírus da imunodeficiência humana: uma visão geral das drogas atuais e novas perspectivas

Introduction: Since its discovery in the 1980s, the human immunodeficiency virus (HIV) has been the target of many studies. Nowadays, estimates show that 36.7 million people are infected with HIV worldwide. In Brazil, HIV infection overcomes 840 thousand people. Globally, only 53% of the HIV infected people are under antiretroviral therapy. Significant advances in antiretroviral therapy have been made since the introduction of zidovudine in 1987. Objective: To advance the discoveries of the available antivirals demonstrating their functional specificities. Methods: We performed a systematic review with a bibliographic survey in the Index Medicus/MEDLINE and PubMed databases for periodical and indexed articles, from 2013 to 2018 that reported on antiretrovirals used or not in the clinical practice. Results: Currently, there are six classes of antiretroviral drugs: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), entry inhibitors (CCRIs), and HIV integrase strand transfer inhibitors (INIs or INSTIs). In summary, several antiretroviral agents under development make HIV entry, reverse transcription, integration, and maturation emerging drug become targets. Conclusion: A multifaceted approach to antiretroviral therapy, using combinations of inhibitors that target different steps of the viral life cycle, has the best potential for long-term control of HIV infection.

Introdução: Desde sua descoberta na década de 1980, o vírus da imunodeficiência humana (HIV) tem sido alvo de muitos estudos. Atualmente, as estimativas mostram que 36,7 milhões de pessoas estão infectadas pelo HIV em todo o mundo. No Brasil, a infecção pelo HIV supera 840 mil pessoas. Globalmente, apenas 53% das pessoas infectadas pelo HIV estão sob terapia antirretroviral. Avanços significativos na terapia antirretroviral (TARV) foram feitos desde a introdução da zidovudina (AZT) em 1987. Objetivo: O objetivo deste estudo foi descrever a descoberta dos antivirais disponíveis atualmente, demonstrando suas especificidades funcionais. Métodos: Foi realizada uma revisão sistemática com levantamento bibliográfico nas bases de dados Index Medicus/MEDLINE e PubMed para artigos periódicos e indexados, no período de 2013 a 2018, que relataram antirretrovirais utilizados ou não na prática clínica. Resultados: Atualmente, existem seis classes de medicamentos antirretrovirais: inibidores nucleosídeos da transcriptase reversa (NRTIs), inibidores não-nucleosídeos da transcriptase reversa (NNRTIs), inibidores da protease (IPs), inibidores de fusão (FIs), inibidores de entrada (CCRIs) e transferência da cadeia da integrase do HIV inibidores (INIs ou INSTIs). Em resumo, vários agentes antirretrovirais em desenvolvimento fazem da entrada do HIV, da transcrição reversa, da integração e da maturação, alvos dos medicamentos emergentes. Conclusão: Uma abordagem multifacetada para a TAR, usando combinações de inibidores que visam diferentes etapas do ciclo de vida viral, tem o melhor potencial para o controle da infecção pelo HIV a longo prazo.

Pattern of cytokine and chemokine production by THP-1 derived macrophages in response to live or heat-killed Mycobacterium bovis bacillus Calmette-Guérin Moreau strain

Tuberculosis has great public health impact with high rates of mortality and the only prophylactic measure for it is the Mycobacterium bovisbacillus Calmette-Guérin (BCG) vaccine. The present study evaluated the release of cytokines [interleukin (IL)-1, tumour necrosis factor and IL-6] and chemokines [macrophage inflammatory protein (MIP)-1α and MIP-1β] by THP-1 derived macrophages infected with BCG vaccine obtained by growing mycobacteria in Viscondessa de Moraes Institute medium medium (oral) or Sauton medium (intradermic) to compare the effects of live and heat-killed (HK) mycobacteria. Because BCG has been reported to lose viability during the lyophilisation process and during storage, we examined whether exposing BCG to different temperatures also triggers differences in the expression of some important cytokines and chemokines of the immune response. Interestingly, we observed that HK mycobacteria stimulated cytokine and chemokine production in a different pattern from that observed with live mycobacteria.

Oral bacillus Calmette-Guérin vaccine against tuberculosis: why not?

The bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine for human use against tuberculosis (TB). Although controversy exists about its efficacy, the BCG vaccine is able to protect newborns and children against disseminated forms of TB, but fails to protect adults against active forms of TB. In the last few years, interest in the mucosal delivery route for the vaccine has been increasing owing to its increased capacity to induce protective immune responses both in the mucosal and the systemic immune compartments. Here, we show the importance of this route of vaccination in newly developed vaccines, especially for vaccines against TB.