Extracellular Vesicles as a New Promising Therapy in HIV Infection

Combination antiretroviral therapy (cART) effectively blocks HIV replication but cannot completely eliminate HIV from the body mainly due to establishment of a viral reservoir. To date, clinical strategies designed to replace cART for life and alternatively to eliminate the HIV reservoir have failed. The reduced expression of viral antigens in the latently infected cells is one of the main reasons behind the failure of the strategies to purge the HIV reservoir. This situation has forced the scientific community to search alternative therapeutic strategies to control HIV infection. In this regard, recent findings have pointed out extracellular vesicles as therapeutic agents with enormous potential to control HIV infection. This review focuses on their role as pro-viral and anti-viral factors, as well as their potential therapeutic applications.

Pulmonary Immune Dysregulation and Viral Persistence During HIV Infection

Despite the success of antiretroviral therapy (ART), people living with HIV continue to suffer from high burdens of respiratory infections, lung cancers and chronic lung disease at a higher rate than the general population. The lung mucosa, a previously neglected HIV reservoir site, is of particular importance in this phenomenon. Because ART does not eliminate the virus, residual levels of HIV that remain in deep tissues lead to chronic immune activation and pulmonary inflammatory pathologies. In turn, continuous pulmonary and systemic inflammation cause immune cell exhaustion and pulmonary immune dysregulation, creating a pro-inflammatory environment ideal for HIV reservoir persistence. Moreover, smoking, gut and lung dysbiosis and co-infections further fuel the vicious cycle of residual viral replication which, in turn, contributes to inflammation and immune cell proliferation, further maintaining the HIV reservoir. Herein, we discuss the recent evidence supporting the notion that the lungs serve as an HIV viral reservoir. We will explore how smoking, changes in the microbiome, and common co-infections seen in PLWH contribute to HIV persistence, pulmonary immune dysregulation, and high rates of infectious and non-infectious lung disease among these individuals.

Quantification of Total HIV DNA as a Marker to Measure Viral Reservoir: Methods and Potential Implications for Clinical Practice

The focus of this review is to examine the importance of quantifying total HIV DNA to target the HIV reservoir and the clinical implications and challenges involved in its future application in clinical practice. Despite intrinsic limitations, the quantification of total HIV DNA is currently the most widely used marker for exploring the HIV reservoir. As it allows estimating all forms of HIV DNA in the infected cells, total HIV DNA load is the biomarker of the HIV reservoir that provides most of the insights into HIV pathogenesis. The clinical role of total HIV-DNA in both untreated and treated patients is extensively supported by important lines of evidence. Thus, predictive models that include total HIV DNA load together with other variables could constitute a prognostic tool for use in clinical practice. To date, however, this marker has been primarily used in experimental evaluations. The main challenge is technical. Although the implementation of droplet digital PCR could improve analytical performance over real-time PCR, the lack of standardization has made cross-comparisons of the data difficult. An effort by investigators to compare protocols is needed. Furthermore, the main effort now should be to involve the biomedical industry in the development of certified assays for in vitro diagnostics use.

Are HIV-1-Specific Antibody Levels Potentially Useful Laboratory Markers to Estimate HIV Reservoir Size? A Review

Despite the benefits achieved by the widespread availability of modern antiretroviral therapy (ART), HIV RNA integration into the host cell genome is responsible for the creation of latent HIV reservoirs, and represents a significant impediment to completely eliminating HIV infection in a patient via modern ART alone. Several methods to measure HIV reservoir size exist; however, simpler, cheaper, and faster tools are required in the quest for total HIV cure. Over the past few years, measurement of HIV-specific antibodies has evolved into a promising option for measuring HIV reservoir size, as they can be measured via simple, well-known techniques such as the western blot and enzyme-linked immunosorbent assay (ELISA). In this article, we re-visit the dynamic evolution of HIV-1-specific antibodies and the factors that may influence their levels in the circulation of HIV-positive individuals. Then, we describe the currently-known relationship between HIV-1-specific antibodies and HIV reservoir size based on study of data from contemporary literature published during the past 5 years. We conclude by highlighting current trends, and discussing the individual HIV-specific antibody that is likely to be the most reliable antibody for potential future utilization for quantification of HIV reservoir size.