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Despite the transformative impact of combination antiretroviral therapy (cART) in improving survival and systemic viral suppression, human immunodeficiency virus (HIV) continues to pose major global health challenges, particularly through its persistent effects on the central nervous system (CNS). The neurological complications associated with HIV, collectively termed neuroAIDS, remain a significant clinical concern due to the CNS’s role as a reservoir for latent infection. This sanctuary status is facilitated by the restrictive nature of the blood-brain barrier and the long-lived persistence of infected microglia, macrophages, astrocytes, and resting CD4+ T cells. Mechanisms of viral entry into the CNS—such as the “Trojan Horse” hypothesis and direct transcytosis—enable early seeding of the brain, complicating long-term viral eradication efforts. While antiretroviral therapy (ART) regimens with higher CNS penetration effectiveness (CPE) scores are generally more successful in suppressing cerebrospinal fluid (CSF) viral loads, neurotoxicity associated with some high-CPE agents underscores the delicate balance between efficacy and safety. Therapeutic challenges also include incomplete CNS drug penetration, the evolution of compartmentalized drug-resistant viral variants, and adverse interactions with treatments for comorbid conditions, all of which limit full neurocognitive recovery. This chapter reviews the recent therapeutic advances aimed at overcoming these barriers, including intensified ART regimens, CCR5 antagonists, nanoparticle-based CNS drug delivery, gene-editing strategies, neuroprotective interventions, and immunomodulatory therapies. By examining these emerging approaches through a global health lens, we explore their potential to inform more effective, accessible, and sustainable strategies for the management of neuroAIDS—ultimately progressing toward the goal of long-term remission and a functional cure.
Centre for Advanced Research (CFAR), Faculty of Medicine, King George’s Medical University (KGMU), Lucknow, India
† Contributed equally to the chapter
Arpita S. Harnam
Centre for Advanced Research (CFAR), Faculty of Medicine, King George’s Medical University (KGMU), Lucknow, India
Hari Kishan
Centre for Advanced Research (CFAR), Faculty of Medicine, King George’s Medical University (KGMU), Lucknow, India
Shailendra K. Saxena
*
Centre for Advanced Research (CFAR), Faculty of Medicine, King George’s Medical University (KGMU), Lucknow, India
† Contributed equally to the chapter
*Address all correspondence to: shailen@kgmcindia.edu
1. Introduction
Human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system, CD4+ T cells, and causes progressive immunodeficiency. Acquired immunodeficiency syndrome (AIDS) is a very late stage of the HIV infection, which is extremely immunosuppressed and vulnerable to opportunistic diseases and cancer. By 2024, there will be about 39 million individuals residing with HIV across the world, and it is estimated that 630,000 deaths related to AIDs will occur within the same year, notwithstanding the excellent advancements in prevention, testing, and treatment interventions. The virus is spread by the means of certain body fluids such as blood, semen, vaginal secretions, and breast milk and may also be transferred by mother to child during pregnancy, childbirth, or breastfeeding. Hugging, kissing, or sharing food do not aid transmission since it is casual. Combination antiretroviral therapy (cART) is the most significant way of managing HIV infection and thereby slowing down the progression of the disease by inhibiting the synthesis of the virus and also restoring the immune system. The current definition of advanced HIV disease (AHD) as provided by the World Health Organization (WHO) is a CD4+ cell count below 200 cells/mm3 or the occurrence of WHO clinical stage 3 or 4 ailments in adults and adolescents. Moreover, children less than 5 years old who have HIV are all considered to have an advanced HIV disease since they are more susceptible [1]. NeuroAIDS is a term used to describe the range of neurological conditions linked to HIV infection. These complications comprise cognitive, motor, and behavioral dysfunctions, which occur as the virus affects the central and peripheral nervous systems [2]. It includes conditions such as HIV-associated neurocognitive disorders (HAND) and HIV-associated dementia (HAD), manifested through cognitive and motor disabilities caused by the effects of HIV on the central nervous system [3]. Other symptoms are peripheral neuropathies, opportunistic infections (tuberculous and cryptococcal meningitis), and AIDS dementia complex [4]. HIV/AIDS management is based on antiretroviral therapy (ART), a combination of medications meant to interfere with various HIV life cycle stages. Its main objective is to inhibit viral replication, rebuild and maintain immune activity, and prevent morbidity and death related to HIV. The cART, previously referred to as highly active antiretroviral therapy (HAART), has played an incredible role in reducing the prevalence of AIDS-defining conditions, including neurological complications like AIDS dementia complex (ADC) and HIV-associated neurocognitive disorders (HAND). ART is not only associated with decreased plasma viral load but also with reduced HIV replication in the central nervous system (CNS), resulting in improved neurological function and a significant decrease in opportunistic infections of the CNS [5, 6, 7].
HIV is a neurotropic virus and can penetrate the brain in 1–2 weeks following its systemic infection. Despite the availability of HAART, HIV disease still continues to prevail in the CNS, and CNS-related neurological issues are still present [8]. HIV can evade the intense blood-brain barrier (BBB) and enter the brain (Figure 1). Major pathways proposed for HIV entry into the brain (Table 1).
Figure 1.
Mechanisms of HIV entry into the CNS and establishment of viral reservoirs in the brain. (A) The mechanisms by which HIV crosses the blood-brain barrier (BBB). In the periphery, HIV infects CD4+ T lymphocytes and monocytes, which releases viral proteins such as Tat and inflammatory cytokines. These HIV-infected monocytes and lymphocytes migrate across the BBB, aided by BBB disruption and cytokine signaling, and differentiate into infected macrophages within the brain parenchyma. (B) Establishes persistent viral reservoirs in the central nervous system (CNS). Another way HIV crosses the BBB is via brain microvascular endothelial cells (BMVEC) through transcytosis. Once within the CNS, HIV infects resident microglia, macrophages, and astrocytes, which acts as long-lived viral reservoirs. These infected glial cells contribute to chronic neuroinflammation through sustained production of chemokines and cytokines, exacerbating neuronal dysfunction and contributing to the development of HIV-associated neurocognitive disorders (HAND).
Step
Performers
Procedure
Peripheral infection
CD4+ T cells, monocytes
HIV infects circulating CD4+ T-lymphocytes and monocytes, and releases Tat and cytokines
BBB crossing
Infected monocytes (“Trojan Horse”)
Monocytes transmigrate into the CNS via disrupted tight junctions (occludin/ZO-1)
Cell-free transcytosis
HIV virions, BMVEC
Direct uptake and transcytosis through brain microvascular endothelial cells
Differentiation in the brain
Monocyte → macrophage
Transmigrated monocytes differentiate into perivascular macrophages, and harbor latent virus
Infection of resident glia
Microglia, astrocytes
Virus spreads to microglia and astrocytes; astrocyte infection via endocytosis or cell-cell contact
Reservoir establishment
Microglia, macrophages, astrocytes, and memory CD4+ T cells
Long-lived cells maintain a latent provirus and can reactivate under inflammatory/immune stimuli
Neuroinflammatory amplification
Cytokines, chemokines, and viral proteins
Infected glia releases inflammatory mediators and exosomes → neuronal injury → HAND
Table 1.
Mechanisms of HIV entry into the CNS and reservoir establishment.
2.1.1 Trojan Horse hypothesis
This hypothesis proposes that the brain becomes infected as HIV-infected immune cells, particularly monocytes and lymphocytes, migrate across the BBB [9]. HIV-infected monocytes and T-lymphocytes have been hypothesized to be important in the transfer of HIV into the CNS. Various adhesion molecules, tight junction proteins, and chemokine receptors are expressed to a higher degree in the HIV infected monocytes (CD14+ and CD16+), facilitating their transmigration into the CNS [10].
2.1.2 Cell-free virus entry into CNS
The HIV components in the blood can penetrate the brain through the brain microvascular endothelial cells (BMVEC), which form the BBB, can internalize HIV particles into intracellular vacuoles, and transport them across the BBB via transcytosis. Although BMVECs typically lack CD4 receptors, HIV entry occurs through alternative pathways such as adsorptive endocytosis mediated by gp120. However, the majority (over 99%) of the internalized virus is subsequently degraded in lysosomes, with less than 1% successfully traversing the endothelial layer to reach the brain parenchyma [11]. BMVECs usually do not express CD4 receptors, and the entry of HIV into these cells is not blocked by chemokines or CD4-targeting inhibitors. Other cell surface molecules, such as the C-type lectins DC-SIGN and L-SIGN, and cell-surface proteoglycans, are more likely to mediate HIV attachment and entry [12]. Despite this, the majority of the virus internalized in the BMVECs is degraded in lysosomes, and it is believed that fewer than 1 percent of the virus that gets through successfully crosses the BMVEC layer [13].
2.2 HIV reservoirs and viral persistence in the brain
Some of the HIV reservoirs in the body include the brain and the gut, where the virus may remain despite ART. This survival makes it difficult to cure HIV because the infection returns rapidly when treatment is not continually followed or discontinued [8]. A virus might remain in the gut due to certain genetic variations among the various sections of the gut [14]. Similarly, HIV can also become compartmentalized in the brain, and the virus can evolve in the same way, which allows the virus to escape the clearance mechanism of the body. This gives rise to a different form of a virus that can only multiply in the case of a weak immune system [15]. In CNS, HIV infects both microglia and monocyte-derived macrophages that serve as key cellular reservoirs, producing inflammatory mediators like IL-18, IL-1β, and caspase-1 via NLRP3 inflammasome activation, contributing to neuroinflammation and neuronal damage [16]. HIV susceptible macrophages and microglia migrate to the site of infection and release inflammatory superoxide due to the HIV negative regulatory factor (Nef) protein [17]. Monocytes that enter the CNS to differentiate into macrophages undergo β-catenin downregulation, making them more susceptible to HIV infection [18]. HIV-infected macrophages resist apoptosis and immune clearance, maintaining latent infection under ART, with factors like leukotriene C4 facilitating infected CD4+ T cell trafficking into the brain and viral spread to resident macrophages and microglia [19, 20]. Astrocytes, the most abundant glial cells in the brain, despite a low HIV integration rate (0.1–1%), constitute a significant reservoir due to their abundance, confirmed by techniques such as in situ hybridization and RNA/DNA scope [21]. Infected astrocytes disrupt the BBB, impair gap junctions, and drive neuroinflammation via altered β-catenin signaling, while latency-reversing agents (LRAs) can reactivate HIV within them [22, 23]. Astrocytes can also transfer HIV to CD4+ T cells, potentially reseeding peripheral infection during treatment interruptions. Though lacking classic HIV entry receptors, astrocytes acquire HIV through pH-dependent endocytosis or direct contact with infected T cells [24, 25]. HIV is primarily maintained in a small fraction (<0.05%) of resting CD4+ T cells, particularly long-lived memory CD4+ T cells, which harbors an integrated but transcriptionally silent HIV-1 provirus. Despite their low frequency, these cells represent a major obstacle to viral eradication. Naive CD4+ T cells are generally CCR5-negative, while memory CD4+ T cell subsets can express variable levels of both CCR5 and CXCR4, with CCR5 expression particularly associated with the activated and effector memory subsets. Memory CD4+ T cells are especially suited to maintain latency due to their longevity and quiescent state, which supports minimal viral transcription and evades immune detection. These cells can produce low levels of virus, potentially reseeding infection, and can reactivate under immune stimulation [26].
The most conventional treatment of HIV infection is through ART. It implies a combination of drugs that act on various stages of the HIV life cycle with the aim of inhibiting viral replication, lowering viral load, and restoring immune function. Standard ART regimens for neuroAIDS have historically included two nucleoside analogues (NAs), such as zidovudine or stavudine, which were among the first agents shown to penetrate the CSF and exert a beneficial effect on HIV-associated brain disease. However, due to the significant long-term toxicities, including mitochondrial toxicity and bone marrow suppression, these agents have largely been phased out of modern treatment protocols. Contemporary guidelines now favor better-tolerated NRTIs such as tenofovir and emtricitabine or lamivudine. Protease inhibitors (PIs) have been variably used for CNS protection, though their value remains under evaluation. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), particularly nevirapine and efavirenz, were historically regarded as CNS-active agents. While combinations of two NAs and one NNRTI were once widely recommended, modern first-line regimens now prioritize integrase strand transfer inhibitors (INSTIs) due to their superior efficacy, tolerability, and favorable CNS penetration profiles. Nevertheless, historical regimens and their CNS penetration data remain relevant in understanding neuroAIDS management evolution and guiding care in resource-limited settings where older drugs may still be in use [27].
The application of ART has revolutionized the process of managing HIV and its related neurological disorders, collectively referred to as neuroAIDS. With the advent of HAART, the CNS has emerged as a key sanctuary site of HIV-1, thus rendering CNS-active ART regimens as crucial determinants of prophylaxis and treatment of HAND and AIDS dementia complex (ADC) [28].
A combination of two NAs and one NNRTI is usually suggested, particularly among patients with high plasma viral loads and some abnormalities of the neurologic system. But it is accompanied by a subpopulation of non-responders who have to be offered other or supplementary treatments [28].
The success of using ART in the treatment of neuroAIDS is closely correlated with the capacity of antiretroviral drugs to cross the CNS barrier. This will be quantified through CNS penetration effectiveness (CPE) score, which is used to rank ART drugs in terms of chemical properties, CSF concentrations, and clinical efficacy in the CNS. The CNS penetration values of each ART drug come out as a CPE score of between 1 (below average) and 4 (much above average). Higher cumulative CPE score drugs (zidovudine, nevirapine, and ritonavir-boosted indinavir) are linked to interventions that result in better suppression of HIV in the CSF, while poor CNS penetration permits further replication of HIV in the CNS, which results in increased CSF HIV viral loads and possibly poorer neurocognitive outcomes [29, 30].
Although higher CPE regimens are usually associated with better CSF virus suppression, there are inconsistent results on their effects on neuropsychological performance. Other high-CNS penetrating regimens have been linked to worse neuropsychological results, which might exist due to neurotoxicity of some agents. The correlation between CSF drug concentrations and those of the actual brain tissue is not well understood, and there are mechanisms through which drugs can be restricted from gaining access to the brain, for example, protein pump (e.g., P-glycoprotein) [29]. Adjunctive therapies are also under investigation to target neuroinflammation and neuroprotection, although none have so far consistently shown clinical benefit in large studies.
Inadequate penetration of drugs into the CNS remains a major therapeutic challenge in managing neuroAIDS, as the BBB restricts many agents from achieving effective concentrations in CSF. Certain classes of efflux transporters, such as those of P-glycoprotein, MRP, and BCRP, actively pump drugs such as ritonavir and saquinavir out of the brain, and physicochemical characteristics such as increased molecular size and reduced lipophilicity further impede passive diffusion. For instance, tenofovir disoproxil fumarate achieves CSF concentrations of less than 7 ng/mL, a fraction of its plasma concentration, which may be insufficient for optimal viral suppression in the CNS. Although regimens with greater CPE scores can enhance suppression of CSF viral loads, clinical benefits remain inconsistent, and neurotoxicity risks from certain high-CPE agents persist, for example, efavirenz [31, 32]. This limited entry enables HIV reservoirs to exist in microglia and perivascular macrophages, supporting low-level viral replication and clonal expansion. Compounding this issue, subtherapeutic levels of ART in the CNS promote the independent evolution of HIV-1, predisposing the selection of resistance mutations that subsequently can expand systemically. Concordant resistance mutations have been reported in CSF and plasma to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs), with ART itself an increasing risk factor for CSF resistance (OR = 4.25) because of partial suppression [33]. Also, long-term ART treatment is the cause of CNS complications through mitochondrial disease since NRTIs such as zidovudine block mitochondrial DNA polymerase-γ, which causes oxidative stress and neuronal damage, whereas protease inhibitors, like darunavir, disintegrate the BBB, triggering microglia, increasing the levels of neurofilament light chains in CSF. Efavirenz is a notable example, associated with neuropsychiatric adverse effects including depression, hallucinations, and vivid dreams in up to 40% of patients, particularly during the early phases of treatment or in antiretroviral-naïve individuals. These effects are thought to be mediated through NMDA receptor modulation and serotonergic pathways, and while often transient, can lead to poor adherence or necessitate regimen changes in the affected individuals. Drug-drug interactions and co-infections further complicate the management of neuroAIDS; ritonavir-enhanced regimens have the effect of inhibiting CYP3A4, thereby increasing the neurotoxic levels of drugs such as sertraline and anticonvulsants. Other risks include co-infections like tuberculosis, whereby rifampicin reduces the nevirapine concentrations by 37%, which leads to the increased risk of virologic failure in the CNS, and hepatitis C co-infection that complicates ART because of the risk of hepatotoxicity and neuroinflammation caused by HCV that aggravates HIV-associated neurocognitive disorders (HAND). The continued inflammation in the CNS with the development of ART, evidenced in elevated CSF myoinositol/creatinine ratios, also makes the effective treatment of neuroAIDS complicated due to these co-morbidities [31, 32]. ART challenges and emerging neuroAIDS strategies are shown in Table 2.
Although the introduction of cART in managing HIV disease has transformed the disease by improving life expectancy, there are still many challenges in managing HIV-related neurological comorbidities (neuroAIDS). These challenges involve the existence of the CNS as the viral reservoir, the BBB obstacle to successful pharmaceutical entry, and chronic neuroinflammation and neurotoxicity despite the viral suppression [34]. In response to these persistent issues, recent advances and emerging strategies in ART for neuroAIDS focus on improving cART efficacy within the CNS, developing novel drug delivery methods, repurposing existing drugs to target downstream neuropathogenesis, and exploring the non-pharmacological interventions.
5.1 Enhancing CNS penetrance
In recent ART advances, drug penetration into the CNS has been approached by improving the passage of drugs through the BBB to achieve better drug access to HIV reservoirs in the CNS. The concept of CPE scores has been developed to rank antiretroviral drugs based on their ability to penetrate the BBB. While the clinical significance of CPE in terms of reducing HAND symptoms is not entirely clear, and some studies show paradoxical associations, some evidence suggests that higher CPE may correlate with better CNS HIV suppression and potential benefits for HIV-associated neurocognitive impairment (HIV-NCI) [34]. Newer integrase strand transfer inhibitors (INSTIs), including elvitegravir, have shown better CNS penetration, particularly when given in an enhanced delivery formulation [35, 36]. Second-generation INSTIs have become preferred in most first-line regimens, and a dose adjustment is being contemplated in the case of CNS resistance. However, the optimization of CNS penetration should be balanced with the risk of neurotoxicity, with a subset of high-penetrance agents (e.g., dolutegravir, efavirenz) leading to the neuropsychiatric adverse effects [35].
5.2 Chemokine receptor blockade
ART intensification with the use of the CCR5 chemokine receptor antagonist maraviroc, an HIV-entry inhibitor, was studied as a method of minimizing the risk of HIV-NCI. Pilot studies demonstrated the promising effects, with cognitive outcomes in virally suppressed people with HAND, with or without an associated improvement in inflammatory biomarkers. There is enthusiasm for CCR5 blockade in general neuroinflammatory disorders. The dual CCR2 and CCR5 antagonist cenicriviroc inhibits not only HIV infection but also inflammation and monocyte migration. In a pilot trial in virally suppressed individuals with mild-to-moderate HIV-NCI, small positive changes in neurocognitive performance and a reduction in plasma measures of monocyte activation markers were observed. The potential neuroprotective effects of blocking both CCR5 and CCR2 are being considered for larger studies [34].
5.3 Nanoparticle-based drug delivery
Nanoparticle-based drug delivery systems target to enhance the distribution of ARV drugs in the brain and have the following advantages: enhanced bioavailability, extended circulation time, and targeting capabilities [36]. Poloxamer-PLGA and nanodiamonds are the nanoparticles (NPs) that have been designed to deliver ART drugs such as efavirenz and elvitegravir across the BBB and exhibit greater uptake and inhibition of viruses in vitro, in HIV-infected macrophages, and in vivo [35, 37, 38]. Liposome-based nanomedicines play a critical role in the delivery of hydrophobic antiviral HIV drugs (i.e., zidovudine, zalcitabine, didanosine) across the BBB, and the stability and circulation of these drugs can be enhanced by making alterations such as PEGylation [39]. Magnetic nanoparticles (MNPs) such as magnetite (Fe3O4) and maghemite (γ-Fe2O3) provided the targeted drug delivery with the capacity of external guidance and simultaneous monitoring via MRI [39]. nanoART may also be ex vivo loaded into cell-mediated delivery mononuclear phagocytes (MP) such as dendritic cells, monocytes, and macrophages that once re-introduced to the body can cross the BBB and deposit drugs locally at sites of infection and can sustain the therapeutic levels of drugs in the CNS over prolonged periods of time [37]. This has been done with nanosuspensions of ritonavir and efavirenz [39]. To increase the uptake by HIV-infected cells and increase specificity of targeting, NP surfaces are being modified with ligands (e.g., mannose, tuftsin) [40].
5.4 Targeting downstream pathways and repurposing existing drugs
Drugs like baricitinib (JAK1/2 inhibitor) have shown the ability to cross the BBB and reduce HIV persistence in the CNS in preclinical and early clinical studies, with ongoing trials assessing their impact on neurocognitive outcomes [41]. The neuroprotective agents (minocycline, selegiline, and statins) have been evaluated in their neuroprotective or anti-inflammatory properties, but clinical trials have not shown definite cognitive effects of drugs in HAND [35, 42]. Probiotic supplementation has shown early evidence of decreasing CSF neopterin concentration and improving neurocognitive performance in small pilot studies [34].
5.5 Gene therapy and immunotherapeutic approaches
CRISPR/Cas9 gene-editing technology is being explored to disrupt HIV proviral DNA or modify host genes such as CCR5 to confer resistance to infection. Early clinical trials have demonstrated the feasibility of infusing gene-edited immune cells to reduce viral loads and enhance resistance in patients. However, concerns regarding off-target effects, immune responses, and safety in CNS applications remain significant hurdles for clinical translation [43, 44]. Metabolic Therapies Shock-and-kill tactics employ latency-reversing agents (LRAs) to re-activate dormant HIV in CNS reservoirs, as well as subsequent eradication by immune responses or suicide gene therapy. However, the reactivation in the CNS can lead to unacceptable neuron injury and inflammation, and this factor presents a considerable safety issue [35, 43]. Additional strategies, including therapeutic vaccines, cytokine therapies (e.g., IL-7, IL-15, IL-21), broadly neutralizing antibodies, and immune checkpoint modulation, are also under investigation for their potential to augment immune clearance of infected cells within the CNS. Antibody-based therapies and immune checkpoint modulation are also being studied to enhance the immune system targeting HIV-infected cells [44, 45].
Despite remarkable advances in cART transforming HIV from a fatal disease into a manageable chronic infection in regions with consistent access to ART, significant challenges remain in addressing the neurological complications collectively known as neuroAIDS. The CNS serves as a critical viral reservoir, sheltering HIV within long-lived cells such as microglia, macrophages, astrocytes, and resting memory CD4+ T cells, where the virus persists in a latent state, often inaccessible to standard ART regimens. While higher CNS-penetrating antiretrovirals offer improved CSF viral suppression, their clinical impact on neurocognitive outcomes remains inconsistent, with certain high-penetrance agents associated with neurotoxicity. Persistent neuroinflammation, the emergence of drug-resistant viral variants within the CNS, and complex drug-drug interactions further complicate long-term management. However, recent advances in CNS-targeted drug delivery systems, such as nanoparticle-based formulations and cell-mediated therapies, alongside novel strategies such as CCR5 and CCR2 antagonism, gene-editing technologies, and immunomodulatory approaches, offer promising avenues to overcome these barriers. Moving forward, future strategies must focus on improving CNS drug bioavailability, effectively targeting latent reservoirs, mitigating chronic neuroinflammation, and integrating multimodal therapies to reduce the burden of HAND. A multidisciplinary, globally coordinated effort will be essential to refine therapeutic strategies, translate emerging interventions into clinical practice, and ultimately improve the quality of life and neurological health outcomes for people living with HIV.
The management of neuroAIDS remains a significant challenge despite the success of cART. Future strategies must prioritize the development of antiretroviral agents with enhanced CNS penetration and minimized neurotoxicity, along with innovative drug delivery systems such as nanoparticle-based formulations to effectively target latent viral reservoirs within the brain. Promising avenues include gene-editing technologies, CCR5/CCR2 receptor antagonists, immunotherapies, and neuroprotective agents aimed at suppressing viral persistence and mitigating chronic neuroinflammation. The integration of these emerging interventions into personalized, CNS-focused treatment regimens should be supported by well-designed multicentric clinical trials and translational research programs to validate their safety, efficacy, and long-term impact on neurocognitive outcomes, ultimately advancing the field toward a functional cure for HIV.
The authors are grateful to the Vice Chancellor, King George’s Medical University (KGMU), Lucknow, for the encouragement and support for this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
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Written By
Jitesh Yadav, Arpita S. Harnam, Hari Kishan and Shailendra K. Saxena
Submitted: 28 July 2025Reviewed: 16 October 2025Published: 13 November 2025
Open access peer-reviewed chapter
