Joseph Hokello

The theory of immune regulation involves a homeostatic balance between T-helper 1 (Th1) and T-helper 2 (Th2) responses. The Th1 and Th2 theories were introduced in 1986 as a result of studies in mice, whereby T-helper cell subsets were found to direct different immune response pathways. Subsequently, this hypothesis was extended to human immunity, with Th1 cells mediating cellular immunity to fight intracellular pathogens, while Th2 cells mediated humoral immunity to fight extracellular pathogens. Several disease conditions were later found to tilt the balance between Th1 and Th2 immune response pathways, including HIV infection, but the exact mechanism for the shift from Th1 to Th2 cells was poorly understood. This review provides new insights into the molecular biology of HIV, wherein the HIV life cycle is discussed in detail. Insights into the possible mechanism for the Th1 to Th2 shift during HIV infection and the preferential infection of Th2 cells during the late symptomatic stage of HIV disease are also discussed.

HIV-exposed seronegative individuals (HESIs) are a small fraction of persons who are multiply exposed to human immunodeficiency virus (HIV), but do not exhibit serological or clinical evidence of HIV infection. In other words, they are groups of people maintaining an uninfected status for a long time, even after being exposed to HIV several times. The long-term non-progressors (LTNPs), on the other hand, are a group of HIV-infected individuals (approx. 5%) who remain clinically and immunologically stable for an extended number of years without combination antiretroviral therapy (cART). Meanwhile, elite controllers are comprise a much lower number (0.5%) of HIV-infected persons who spontaneously and durably control viremia to below levels of detection for at least 12 months, even when using the most sensitive assays, such as polymerase chain reaction (PCR) in the absence of cART. Despite the fact that there is no universal agreement regarding the mechanisms by which these groups of individuals are able to control HIV infection and/or disease progression, there is a general consensus that the mechanisms of protection are multifaceted and include genetic, immunological as well as viral factors. In this review, we analyze and compare the biological factors responsible for the control of HIV in these unique groups of individuals.

The central nervous system (CNS) is highly compartmentalized and serves as a specific site of human immunodeficiency virus (HIV) infection. Therefore, an understanding of the cellular populations that are infected by HIV or that harbor latent HIV proviruses is imperative in the attempts to address cure strategies, taking into account that HIV infection and latency in the CNS may differ considerably from those in the periphery. HIV replication in the CNS is reported to persist despite prolonged combination antiretroviral therapy due to the inability of the current antiretroviral drugs to penetrate and cross the blood–brain barrier. Consequently, as a result of sustained HIV replication in the CNS even in the face of combination antiretroviral therapy, there is a high incidence of HIV-associated neurocognitive disorders (HAND). This article, therefore, provides a comprehensive review of HIV transcriptional regulation, latency, and therapy in the CNS.

Unsafe sex with HIV-infected individuals remains a major route for HIV transmission, and protective strategies, such as the distribution of free condoms and pre-or post-prophylaxis medication, have failed to control the spread of HIV, particularly in resource-limited settings and high HIV prevalence areas. An additional key strategy for HIV prevention is voluntary male circumcision (MC). International health organizations (e.g., the World Health Organization, UNAIDS) have recommended this strategy on a larger scale, however, there is a general lack of public understanding about how MC effectively protects against HIV infection. This review aims to discuss the acquisition of HIV through the male genital tract and explain how and why circumcised men are more protected from HIV infection during sexual activity than uncircumcised men who are at higher risk of HIV acquisition.

In 2020, the global prevalence of human immunodeficiency virus (HIV) infection was estimated to be 38 million, and a total of 690,000 people died from acquired immunodeficiency syndrome (AIDS)–related complications. Notably, around 12.6 million people living with HIIV/AIDS did not have access to life-saving treatment. The advent of the highly active antiretroviral therapy (HAART) in the mid-1990s remarkably enhanced the life expectancy of people living with HIV/AIDS as a result of improved immune functions. However, HAART has several drawbacks, especially when it is not used properly, including a high risk for the development of drug resistance, as well as undesirable side effects such as lipodystrophy and endocrine dysfunctions, which result in HAART intolerability. HAART is also not curative. Furthermore, new HIV infections continue to occur globally at a high rate, with an estimated 1.7 million new infections occurring in 2018 alone. Therefore, there is still an urgent need for an affordable, effective, and readily available preventive vaccine against HIV/AIDS. Despite this urgent need, however, progress toward an effective HIV vaccine has been modest over the last four decades. Reasons for this slow progress are mainly associated with the unique aspects of HIV itself and its ability to rapidly mutate, targeting immune cells and escape host immune responses. Several approaches to an HIV vaccine have been undertaken. However, this review will mainly discuss progress made, including the pre-clinical and clinical trials involving vector-based HIV DNA vaccines and the use of integrating lentiviral vectors in HIV vaccine development. We concluded by recommending particularly the use of integrase-defective lentiviral vectors, owing to their safety profiles, as one of the promising vectors in HIV DNA vaccine strategies both for prophylactic and therapeutic HIV vaccines.

The persistence of latent HIV provirus pools in different resting CD4+ cell subsets remains the greatest obstacle in the current efforts to treat and cure HIV infection. Recent efforts to purge out latently infected memory CD4+ T-cells using latency-reversing agents have failed in clinical trials. This review discusses the epigenetic and non-epigenetic mechanisms of HIV latency control, major limitations of the current approaches of using latency-reversing agents to reactivate HIV latency in resting CD4+ T-cells, and potential solutions to these limitations.