Human Immunodeficiency Virus Eradication Research Articles

Use of \u2018eradication\u2019 in HIV cure-related research: a public health debate

BackgroundThe landscape of Human Immunodeficiency Virus (HIV) research has changed drastically over the past three decades. With the remarkable success of antiretroviral treatment (ART) in decreasing AIDS-related mortality, some researchers have shifted their HIV research focus from treatment to cure research. The HIV cure research community often uses the term eradication to describe the science, and talks about eradicating the virus from the body. In public discourse, the term eradication could be conflated with disease eradication at the population level. In this paper, we call for a reframing of HIV cure research as control, as it is a more accurate descriptor and achievable goal in the foreseeable future.DiscussionThe properties of HIV are discordant with eradicability standards at both the individual level (as a clinical concept), and at the population level (as a public health concept). At the individual level, true eradication would necessitate absolute elimination of all latent HIV reservoirs from the body. Current HIV cure-related research strategies have proven unsuccessful at accurately quantifying, let alone eliminating these reservoirs. At the population level, eradication implies the permanent global reduction of HIV to zero new cases and to zero risk for future cases. Given the absence of an efficacious HIV vaccine and the impracticality and unethicality of eliminating animal reservoirs, global eradication of HIV is highly implausible. From a public health perspective, HIV eradication remains an elusive goal.ConclusionThe term ‘eradication’ is a misleading description of current HIV cure-related research. Instead, we call for the use of more realistic expressions such as ‘sustained virologic HIV suppression (or control)’ or ‘management of HIV persistence’ to describe HIV cure-related research. Using these terms reorients what HIV cure science can potentially achieve in the near future and avoids creating unrealistic expectations, particularly among the millions of people globally who live with HIV.

Human Immunodeficiency Virus in the Brain-Culprit or Facilitator?

Introduction:Human immunodeficiency virus (HIV) enters the brain early, where it can persist, evolve, and become compartmentalized. Central nervous system (CNS) disease can be attributed to HIV alone or to the complex interplay between the virus and other neurotropic pathogens.Aim:The current review aims to describe the direct impact of HIV on the brain as well as its relationship with other pathogens from a practitioner’s perspective, to provide a general clinical overview, brief workup, and, whenever possible, treatment guidance.Methods:A review of PubMed was conducted to identify studies on neuropathogenesis of HIV in relation to host responses. Furthermore, the interaction between the CNS pathogens and the host damage responses were revised in the setting of advanced and also well-controlled HIV infection.Results:Similar to other pathogens, HIV leads to CNS immune activation, inflammation, and viral persistence. Therefore, almost half of the infected individuals present with neurocognitive disorders, albeit mild. Compartmentalized HIV in the CNS can be responsible in a minority of cases for the dramatic presentation of symptomatic HIV escape. Disruption of the immune system secondary to HIV may reactivate latent infections or allow new pathogens to enter the CNS. Opportunistic infections with an inflammatory component are associated with elevated HIV loads in the cerebrospinal fluid and also with greater cognitive impairment. The inflammatory immune reconstitution syndrome associated with CNS opportunistic infections can be a life-threatening condition, which needs to be recognized and managed by efficiently controlling the pathogen burden and timely balanced combination antiretroviral therapy. Latent neurotropic pathogens can reactivate in the brain and mimic HIV-associated severe neurological diseases or contribute to neurocognitive impairment in the setting of stable HIV infection.Conclusions:As HIV can be responsible for considerable brain damage directly or by facilitating other pathogens, more effort is needed to recognize and manage HIV-associated CNS disorders and to eventually target HIV eradication from the brain.

Modern biotechnology-based therapeutic approaches against HIV infection.

The causative agent of acquired immune deficiency syndrome (AIDS) is human immunodeficiency virus (HIV). Since its discovery before 30 years, a number of drugs known as highly active antiretroviral therapy have been developed to suppress the life cycle of the virus at different stages. With the current therapeutic approaches, ending AIDS means providing treatment to 35 million individuals living with HIV for the rest of their lives or until a cure is developed. Additionally, therapy is associated with various other challenges such as potential of drug resistance, toxicity and presence of latent viral reservoir. Therefore, it is imperative to search for treatments and to identify new therapeutic approaches against HIV infection to avoid daily intake of drugs. The aim of the current review was to summarize different therapeutic strategies against HIV infection, including stem cell therapy, RNA interference, CRISPR/Cas9 pathways, antibodies, intrabodies and nanotechnology. Silencing RNA against chemokine receptor 5 and other HIV RNAs have been tested and found to elicit homology-based, post-transcriptional silencing. The CRISPR/Cas9 is a gene editing technology that produces a double-stranded nick in the virus DNA, which is repaired by the host machinery either by non-homology end joining mechanism or via homology recombination leading to insertion, deletion mutation which further leads to frame shift mutation and non-functional products. Intrabodies are intracellular-expressed antibodies that are directed towards the targets inside the cell unlike the naturally expressed antibodies which target outside the cell. Different nanotechnology-based therapeutic approaches are also in progress against HIV. HIV eradication is not feasible without deploying a cure or vaccine alongside the treatment.

A pilot molecular mechanism study on lacrimal gland as a potential human immunodeficiency virus reservoir

Background Acquired immune deficiency syndrome (AIDS) is an infectious disease caused by human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is an effective treatment for AIDS, but it cannot completely eliminate the viral load in the body for the existence of HIV reservoir.Previous studies demonstrated that HIV could be detected in tears of virus load negative AIDS patients who received effective HAART, suggesting that lacrimal gland is another member of HIV reservoirs. Objective The aim of this study was to explore whether lacrimal gland has a molecular basis of HIV infection and the mechanism of lacrimal gland infection of HIV. Methods Fourteen specimens of lacrimal gland were collected during the surgery from 14 patients with lacrimal gland diseases in Peking Union Medical College Hospital from November 2013 to December 2015, including 13 non-HIV-infected patients and 1 HIV-infected patient.In 13 non-HIV infected patients, lacrimal glands prolapse was in 12 patients with the normal pathological tissue structure and dacryoadenitis was in 1 patient with the histopathological diagnosis of interstitial lymphoid tissue hyperplasia.The clinical manifestation of HIV-infected patient was dacryoadenitis with the histopathological diagnosis of interstitial lymphoid tissue hyperplasia.The paraffin sections of 12 non-HIV-infected specimens and 1 HIV-infected specimen were prepared, and the expressions of CD4, C-X-C chemokine receptor 4 (CXCR4)and C-C chemokine receptor type 5 (CCR5) in lacrimal gland specimens were detected by immunohistochemistry and verified in 1 specimen of non-HIV-infected specimen by immunofluorescence technology. Results Immunohistochemistry showed that CD4 was suspiciously positive expression in non-HIV-infected specimens with the strong background staining.CXCR4 was positively expressed in cytoplasm and nuclei of most lacrimal epithelial cells of lacrimal gland epithelial cells in each specimen, and CCR5 was focally expressed in few lacrimal gland epithelial cells in each specimen.In addition, CD4, CXCR4 and CCR5 were positively expressed in intercellular scattered lymphocytes on the specimens.Immunofluorescence assay showed that CD4, CXCR4 and CCR5 were expressed in the specimens with the red fluorescence, with the linear- and patchy-like distribution mainly in cellular membrane for CD4 or spot-like distribution for CXCR4 and CCR5 in the cytoplasm. Conclusions HIV receptor CD4 and accessory receptor CXCR4, CCR5 are positively expressed in the lacrimal gland epithelial cells, which is the molecular basis of HIV infection and become a potential HIV reservoir preventing HIV eradication. Key words: Acquired immunodeficiency syndrome/immunology; AIDS-associated ophthalmopathy/metabolism; HIV Infections/metabolism; Virus latency; Tears/virology; Receptors, CD4+ T-lymphocytes/virology; Receptors, CXCR4/metabolism; Receptors, CCR5/metabolism; Lacrimal gland epithelial cells

Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection.

The human immunodeficiency virus (HIV) accesses the central nervous system (CNS) early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency virus (SIV)-infected macaques, a model for HIV infection. We found increased expression of inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV-infected macaques. Conversely, the frontal lobe showed downregulation of inflammatory genes associated with interferon-γ and interleukin-6 pathways, and absence of perivascular cuffing. These immunologic alterations were not accompanied by differences in SIV transcriptional activity within the tissue. Altered expression of genes associated with neurotoxicity was observed in both midbrain and frontal lobe. The segregation of inflammatory responses to specific regions of the CNS may both account for HIV-associated neurological symptoms and constitute a critical hurdle for HIV eradication by shielding the CNS viral reservoir from antiviral immunity.

Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir.

Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects. We focus on strategies that may maximize target recognition and eradication by the sequential activation of a reconstituted immune system, together with delivery of optimal T-cell responses that can eliminate the reservoir and serve as means to maintain control of HIV spread in the absence of antiretroviral therapy (ART). As evidenced by the evolution of ART, we argue that a combination of immune-based strategies will be a superior path to cell-mediated HIV control and eradication. Available data from several human pilot trials already identify target strategies that may maximize antiviral pressure by joining innate and engineered T cell responses toward testing for sustained HIV remission and/or cure.

Occurrence of HIV eradication for preexposure prophylaxis treatment with a deterministic HIV model.

The authors examine the human immunodeficiency virus (HIV) eradication in this study using a mathematical model and analyse the occurrence of virus eradication during the early stage of infection. To this end they use a deterministic HIV-infection model, modify it to describe the pharmacological dynamics of antiretroviral HIV drugs, and consider the clinical experimental results of preexposure prophylaxis HIV treatment. They also use numerical simulation to model the experimental scenario, thereby supporting the clinical results with a model-based explanation. The study results indicate that the protocol employed in the experiment can eradicate HIV in infected patients at the early stage of the infection.

Barriers to HIV Cure.

Since the beginning of the epidemic, more than 70 million people have been infected with human immunodeficiency virus (HIV) and about 38 million have died from acquired immune deficiency syndrome (AIDS)-related illnesses. While the discovery of highly active antiretroviral therapy (HAART) in the mid 90's has saved millions of lives, a complete eradication of HIV is still not possible as HIV can persist for decades in a small reservoir of latently infected cells. Once reactivated, these latently infected cells can actively produce viral particles. Recent studies suggest that several sanctuaries exist within infected individuals where HIV can remain undetected by the immune system. These cellular, anatomical and microanatomical viral reservoirs represent a major obstacle for the eradication of HIV. Here we review recent findings on potential sanctuaries of HIV and address potential avenues to overcome these immunological barriers.

Natural Products as Anti-HIV Agents and Role in HIV-Associated Neurocognitive Disorders (HAND): A Brief Overview.

As the threat of Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) persists to rise, effective drug treatments are required to treat the infected people. Even though combination antiretroviral therapy (cART) provides stable viral suppression, it is not devoid of undesirable side effects, especially in persons undergoing long-term treatment. The present therapy finds its limitations in the emergence of multidrug resistance and accordingly finding new drugs and novel targets is the need of the hour to treat the infected persons and further to attack HIV reservoirs in the body like brain, lymph nodes to achieve the ultimate goal of complete eradication of HIV and AIDS. Natural products such as plant-originated compounds and plant extracts have enormous potential to become drug leads with anti-HIV and neuroprotective activity. Accordingly, many research groups are exploring the biodiversity of the plant kingdom to find new and better anti-HIV drugs with novel mechanisms of action and for HIV-associated neurocognitive disorders (HAND). The basic challenge that still persists is to develop viral replication-targeted therapy using novel anti-HIV compounds with new mode of action, accepted toxicity and less resistance profile. Against this backdrop, the World Health Organization (WHO) suggested the need to evaluate ethno-medicines for the management of HIV/AIDS. Consequently, there is need to evaluate traditional medicine, particularly medicinal plants and other natural products that may yield effective and affordable therapeutic agents. Although there are a good number of reports on traditional uses of plants to treat various diseases, knowledge of herbal remedies used to manage HIV/AIDS and HAND are scanty, vague and not well documented. In this review, plant substances showing a promising action that is anti-HIV and HAND will be explored along with what they interact. Since some plant substances are also known to modulate several cellular factors which are also involved in the replication of HIV and hence their role as potential candidates will be discussed. HIV/AIDS being an exceptional epidemic, demands an exceptional approach and that forms very much focus for the current review.

Dynamics of HIV infection in lymphoid tissue network.

Human immunodeficiency virus (HIV) is a fast replicating ribonucleic acid virus, which can easily mutate in order to escape the effects of drug administration. Hence, understanding the basic mechanisms underlying HIV persistence in the body is essential in the development of new therapies that could eradicate HIV infection. Lymphoid tissues are the primary sites of HIV infection. Despite the recent progress in real-time monitoring technology, HIV infection dynamics in a whole body is unknown. Mathematical modeling and simulations provide speculations on global behavior of HIV infection in the lymphatic system. We propose a new mathematical model that describes the spread of HIV infection throughout the lymphoid tissue network. In order to represent the volume difference between lymphoid tissues, we propose the proportionality of several kinetic parameters to the lymphoid tissues' volume distribution. Under this assumption, we perform extensive numerical computations in order to simulate the spread of HIV infection in the lymphoid tissue network. Numerical computations simulate single drug treatments of an HIV infection. One of the important biological speculations derived from this study is a drug saturation effect generated by lymphoid network connection. This implies that a portion of reservoir lymphoid tissues to which drug is not sufficiently delivered would inhibit HIV eradication despite of extensive drug injection.

Modified Release Biodegradable Polymeric Microspheres of Stavudine: Cell Viability, Cellular Uptake, Hemolysis Studies and In Vivo Pharmacokinetics.

Family of retroviruses which replicates through the use of the reverse transcriptase enzyme or the enzyme needed to convert RNA to DNA for replication bears Human Immunodeficiency Virus (HIV). It causes irreversible destruction of the immune system leading to the occurrence of opportunistic infections and malignancies. The eradication of HIV is highly unlikely as the cells of the mononuclear phagocyte system (MPS) besides CD4 T lymphocytes are the specific hosts for HIV which need to be targeted even after extended blood plasma profile of antiviral drug to maintain viral suppression and reduced disease progression. Aiming the current goal, biodegradable polymeric microspheres of PLGA 50: 50 (RESOMER(®) 505H) were developed and evaluated. These polymeric particles encapsulating Stavudine (d4T) exhibited nearly 100% cell viability during cytotoxicity studies in comparison to pure d4T. The histological studies have revealed the in vivo biocompatibility while hemolysis studies certified the liability of formulation to be used parenteraly exhibiting no significant hemolytic toxixicty. The in vivo pharmacokinetics has shown the extended drug release from microsphere matrix upto a month. The calculated AUCtotal for d4T loaded polymeric microspheres was found to be 3341.656 μM h/ml; which was nearly 54 times than the total AUC of free d4T injected subcutaneously to the control group of animals; exhibiting the stable d4T concentration in blood avoiding fluctuation of the same indicating decreased probabilities of development of resistance against the treatment. Combination of targeted and subcutaneous administration of d4T will not only provide the stable and extended release of drug but also eradicate the hidden HIV hosted by macrophages. The concomitant regimen will potentially enhance the therapeutic efficacy with patient compliance; renewing new hopes for complete cure and improved quality of life in the AIDS patient.

Enhancing Human Immunodeficiency Virus-Specific CD8(+) T Cell Responses with Heteroclitic Peptides.

Human immunodeficiency virus (HIV)-specific CD8+ T cells play a critical role in containing HIV replication and delaying disease progression. However, HIV-specific CD8+ T cells become progressively more “exhausted” as chronic HIV infection proceeds. Symptoms of T cell exhaustion range from expression of inhibitory receptors and selective loss of cytokine production capacity through reduced proliferative potential, impaired differentiation into effector cells and increased susceptibility to apoptosis. While effective combination antiretroviral therapy (cART) durably reduces HIV viremia to undetectable levels, this alone does not restore the full pluripotency of HIV-specific CD8+ T cells. In a number of studies, a subset of peptide epitope variants categorized as heteroclitic, restimulated more potent cellular immune responses in vitro than did the native, immunizing peptides themselves. This property of heteroclitic peptides has been exploited in experimental cancer and chronic viral infection models to promote clearance of transformed cells and persistent viruses. In this review, we consider the possibility that heteroclitic peptides could improve the efficacy of therapeutic vaccines as part of HIV immunotherapy or eradication strategies. We review literature on heteroclitic peptides and illustrate their potential to beneficially modulate the nature of HIV-specific T cell responses toward those found in the small minority of HIV-infected, aviremic cART-naïve persons termed elite controllers or long-term non-progressors. Our review suggests that the efficacy of HIV vaccines could be improved by identification, testing, and incorporation of heteroclitic variants of native HIV peptide epitopes.

Physical and Metabolic Integrity of the Blood-Brain Barrier in HIV Infection: A Special Focus on Intercellular Junctions, Influx and Efflux Transporters and Metabolizing Enzymes.

The advent of highly active antiretroviral therapy has significantly reduced morbidity and mortality in human immunodeficiency virus (HIV) infection. Despite this reduction, complete eradication of HIV from the human body is not feasible in the nearly seen future. The central nervous system (CNS) is protected from blood-borne substances by a subtle structure of vascular endothelia known as blood-brain barrier (BBB). The BBB expresses transporters and metabolizing enzymes that modulate drug permeability in the CNS. This paper reviews the changes of the BBB phenotype as a physical and metabolic barrier in HIV infection. The effects of HIV and its proteins on intercellular junctions, influx and efflux transporters and metabolizing enzymes expressed at the BBB are reviewed. In HIV infection, the integrity of the BBB is severely compromised which often leads to serious neuropathological manifestations in the CNS. HIV and its proteins affect signaling pathways leading to oxidative stress, induction of matrix metalloproteinases and cytokines, down-regulation of different structural components of intercellular junctions, transporters and metabolizing enzymes. Taken together, HIV infection severely disrupts the integrity of the BBB and homeostasis of the CNS leading to modulation of drug disposition in the CNS and neurotoxicity. Applying knowledge of these mechanisms may lead to new therapeutic avenues to reduce neurological complications of HIV infection in the CNS.

Can HIV Be Cured and Should We Try?

An estimated 35.0 million persons live with HIV; 2.1 million new infections occurred and 1.5 million persons died of HIV in 2013 (World Health Organization, http://www.who.int/hiv/data/epi_core_dec2014.png?ua=1). Despite effective combination antiretroviral therapy (cART), less than one-quarter of patients can access these life-prolonging medications; and despite its effectiveness, cART does not normalize life expectancy, as premature aging, metabolic complications and chronic inflammation complicate HIV therapy. HIV is incurable due to the presence of a latent viral reservoir. During the life cycle of the virus, HIV integrates into the host DNA. A subset of integrated HIV provirus remains transcriptionally silent, producing neither viral proteins nor viral progeny, until reactivation by various physiologic stimuli. This latency of HIV allows some infected cells to escape immune detection and elimination, and these latently infected cells constitute the viral reservoir. The latent viral reservoir allows viral rebound within weeks of interruption of cART, 1,2 where the magnitude of viral replication approaches that present pre-therapy. Although it was once thought that viral rebound occurred universally following therapy interruption, several recent reports challenge that paradigm. The “Berlin patient” successfully cleared HIV after two allogeneic transplants from a donor with homozygous CCR5Δ32 mutation,3 and he has not rebounded HIV after nearly seven years. This case likely represents a cure from HIV; yet other cases have been described where HIV rebound has been attenuated, or delayed. The “Mississippi” baby was a perinatally HIV-infected infant who initiated cART within hours of birth, and when interrupted eighteen months later, viremia remained undetectable for nearly two years.4 The Harvard BMT cases underwent allogeneic BMT, developed undetectable HIV DNA, yet rebounded viremia within only eight months after cART discontinuation.5 Together these cases demonstrate that control of viremia in the absence of cART is possible, if not durable.4 The VISCONTI cohort of 14 HIV-infected adults who initiated antiretroviral therapy during acute infection, and in whom high level rebound viremia had not occurred several years after cessation of therapy,6 similarly demonstrated that viral rebound following cART interruption can be attenuated. These cases have reinvigorated research toward finding a cure for HIV, which certainly will require an exceptional investment of time, talent and resources. Thus it is prudent to question whether such resources would be better devoted to more proximate needs with proven results (such as supplying cART to those without access to it, or supplying pre/post exposure prophylaxis to reduce the rate of new infections).

Expanded cytotoxic T-cell lymphocytes target the latent HIV reservoir.

Enhanced human immunodeficiency virus (HIV)-specific immunity may be required for HIV eradication. Administration of autologous, ex vivo expanded, virus-specific, cytotoxic T-lymphocytes derived from HIV-infected patients on suppressive antiretroviral therapy (HXTCs) are a powerful tool for proof-of-concept studies. Broadly specific, polyclonal HXTCs resulting from ex vivo expansion demonstrated improved control of autologous reservoir virus compared to bulk CD8(+) T cells in viral inhibition assays. Furthermore, patient-derived HXTCs were able to clear latently infected autologous resting CD4(+) T cells following exposure to the latency-reversing agent, vorinostat. HXTCs will be ideal reagents to administer with precise control in future in vivo studies in combination with latency-reversing agents.

Focusing National Institutes of Health HIV/AIDS research for maximum population impact.

Progress in advancing research on the pathophysiology, prevention, treatment, and impact of human immunodeficiency virus (HIV) is threatened by the decaying purchasing power of National Institutes of Health (NIH) dollars. A working group of the NIH Office of AIDS Research Advisory Council was charged by the NIH Director with developing a focused and concise blueprint to guide the use of limited funding over the next few years. Science priorities outlined by the working group and reported here are intended to maximally address individuals, groups, and settings most affected by the epidemic, and to redress shortcomings in realizing population-level HIV prevention, treatment, and eradication goals. Optimizing these priorities requires that traditional silos--defined by topic focus and by scientific discipline--be dissolved and that structural issues affecting the pipeline of new investigators and the ability of the Office of AIDS Research to fulfill its role of steward of the NIH HIV/AIDS research program be directly addressed.

Eradication of human immunodeficiency virus from brain reservoirs.

Isolated cases in which human immunodeficiency virus (HIV) infection was claimed to have been eradicated generated renewed interest in HIV reservoirs in the brain particularly since attempts to reproduce the findings using genetically engineered stem cells and immune- or myeloablation have failed. A clear understanding of the cell types in which the virus resides in the brain, the mechanism of viral persistence, restricted replication and latency, and the turnover rate of the infected cells is critical for us to develop ways to control or get rid of the virus in the brain. The brain has several unique features compared to other reservoirs. There are no resident T cells in the brain; the virus resides in macrophages and astrocytes where the viral infection is non-cytopathic. The virus evolves in the brain and since the turnover rate of these cells is low, the virus has the potential to reside in these cells for several decades and possibly for the life of the individual. This review discusses the HIV reservoirs in the brain, issues related to eradication of the virus from sanctuaries in the brain, and current challenges faced by neuroscientists in finding a cure.

Effect of HIV-reactivating agents on blood brain barrier permeability

Soon after primary infection, the human immunodeficiency virus (HIV) crosses the blood–brain barrier (BBB), and then maintains its presence in the brain throughout the individual's life. The brain is an ideal reservoir for HIV where it can escape the immune system and some antiretrovirals. To achieve HIV eradication, it has been suggested that treating patients simultaneously with highly active antiretroviral therapy (HAART) and agents that reactivate latent HIV might eliminate viral reservoirs.

Targeting strategies for delivery of anti-HIV drugs.

Human Immunodeficiency Virus (HIV) infection remains a significant cause of mortality globally. Though antiretroviral therapy has significantly reduced AIDS-related morbidity and mortality, there are several drawbacks in the current therapy, including toxicity, drug–drug interactions, development of drug resistance, necessity for long-term drug therapy, poor bio-availability and lack of access to tissues and reservoirs. To circumvent these problems, recent anti-HIV therapeutic research has focused on improving drug delivery systems through drug delivery targeted specifically to host cells infected with HIV or could potentially get infected with HIV. In this regard, several surface molecules of both viral and host cell origin have been described in recent years, that would enable targeted drug delivery in HIV infection. In the present review, we provide a comprehensive overview of the need for novel drug delivery systems, and the successes and challenges in the identification of novel viral and host-cell molecules for the targeted drug delivery of anti-HIV drugs. Such targeted anti-retroviral drug delivery approaches could pave the way for effective treatment and eradication of HIV from the body.

One Step Closer to HIV Eradication?

In the global fight against HIV/AIDS, the persistence of viral reservoirs, established early during primary infection by the Human Immunodeficiency virus (HIV), is probably the biggest challenge to finding a cure for HIV, despite the major progress provided by antiviral treatments. This persistence reflects virus latency in the immune system and imposes the prospect of life-long treatment with risk of toxicities, and major costs for society. Innovative strategies aimed at purging these viral reservoirs are therefore required, but the complexity of the latency mechanisms has made a sterilization cure difficult to realize until now. However, recent cases of HIV remission have encouraged the research community, and a functional cure seems to be a more realistic goal to attempt. A better understanding of the mechanisms responsible for such latency has been provided by basic research, although recent attempts at purging the reservoirs by disrupting latency have been somewhat disappointing. In contrast, the early initiation of anti-retroviral treatment appears to be extremely beneficial for HIV remission, as recently suggested by the Mississippi baby case or by the series of post-treatment controllers, respectively. Early treatment initiation can indeed rapidly limit the size of viral reservoirs, or hamper their formation and preserve the host’s immune responses. Despite these encouraging results, it is nevertheless important to deploy more effort toward a better understanding of latency mechanisms and to the development of innovative approaches and molecules in the hope of achieving a cure for HIV.