Current status of the small molecule anti-HIV drugs in the pipeline or recently approved.

Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS) with high morbidity and mortality rates. Treatment of AIDS/HIV is being complicated by increasing resistance to currently used antiretroviral (ARV) drugs, mainly in low- and middle-income countries (LMICs) due to drug misuse, poor drug supply and poor treatment monitoring. However, progress has been made in the development of new ARV drugs, targeting different HIV components (Fig. 1). This review aims at presenting and discussing the progress made towards the discovery of new ARVs that are at different stages of clinical trials as of July 2024. For each compound, the mechanism of action, target biomolecule, genes associated with resistance, efficacy and safety, class, and phase of clinical trial are discussed. These compounds include analogues of nucleoside reverse transcriptase inhibitors (NRTIs) - islatravir and censavudine; non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Rilpivirine, elsulfavirine and doravirine; integrase inhibitors namely cabotegravir and dolutegravir and chemokine coreceptors 5 and 2 (CC5/CCR2) antagonists for example cenicriviroc. Also, fostemsavir is being developed as an attachment inhibitor while lenacapavir, VH4004280 and VH4011499 are capsid inhibitors. Others are maturation inhibitors such as GSK-254, GSK3532795, GSK3739937, GSK2838232, and other compounds labelled as miscellaneous (do not belong to the classical groups of anti-HIV drugs or to the newer classes) such as obefazimod and BIT225. There is a considerable progress in the development of new anti-HIV drugs and the effort will continue since HIV infections has no cure or vaccine till now. Efforts are needed to reduce the toxicity of available drugs or discover new drugs with new classes which can delay the development of resistance.

Measurements of Surgical Volume in Low- and Middle-Income Countries, a Systematic Review.

Background: Surgical volume is a surgical indicator that was described in the Lancet Commission on Global Surgery (LCoGS) and the World Bank World Development Indicators as an important metric for tracking the delivery of surgical care. Objectives: We aimed to characterize the reports on surgical volume (SV) in the existing literature by using a systematic review to assess studies that examine surgical procedures as a ratio of a population (procedures/100,000 population). Methods: The PRISMA guideline was employed in the systematic review of articles that addressed the measurement of SV in low- and middle-income countries (LMICs), with the primary outcome of surgical procedures/100,000 population. Findings: The search result consisted of 6,657 preliminary studies. Following the title and abstract screening, 6,464 articles were excluded, and the remaining 193 were included in the full text review. From the full text review of the 193, only 26 of these articles defined SV as the ratio of number of procedures per population of the catchment/geographical area. The reported SV was a mean of 765, with an SD of 1260 operations per 100,000. The median SV was 180 (min = 0.900, max = 4470). Conclusion: Our findings support the LCoGS assessment of the gap in surgical care. The target for SV is 5000 per 100,000 population, compared to the average of 765 per 100,000 population as found in this review. The challenges for assessing surgical volume gaps are vast, including the nature of written records, which limits SV reports to an absolute number of procedures per year without a reference to the catchment population. For the purpose of tracking SV, we recommend using proxies that account for the capacity of facilities to deliver care regardless of the catchment population.