Plasma Virome of HIV-infected Subjects on Suppressive Antiretroviral Therapy Reveals Association of Differentially Abundant Viruses with Distinct T-cell Phenotypes and Inflammation.

Background: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment naïve and immunocompromised (CD4 count < 200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objectives: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods: Plasma viral DNA from PWH on ART and controls was used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.

Humoral and cellular immune response in patients of liver cirrhosis and immunocompetent recipient of ChAdOx1nCoV-19 Vaccine (Covishield).

Despite the effectiveness of COVID-19 vaccination in reducing the severity of the disease, the demand for booster is increasing in vulnerable populations like elderly and immunocompromised individuals especially with each new wave of COVID-19 in different countries. There is limited data on the sustained immunity against COVID-19 in patients with liver cirrhosis. The study was aimed to compare the T cell and humoral immune response after 1 year of ChAdOx1nCoV-19 Vaccine in patients with liver cirrhosis and healthy health care workers (HCW). This was a prospective observational study including 36 HCW, 19 liver cirrhosis patients and 10 unvaccinated individuals. Anti-SARS-CoV-2S antibody, neutralizing antibody and memory T cell subsets were evaluated by ELISA and flow cytometry, respectively, in all three groups after 1 year of initial vaccination. Compared to HCW and unvaccinated individuals, liver cirrhosis patients had significantly depleted T cells, although CD4:CD8 + T cell ratio was normal. Both cirrhotic patients and HCW developed memory T cell subset [effector memory RA (P = 0.141, P < 0.001), effector memory (P < 0.001, P < 0.001), central memory (P < 0.001, P < 0.01), stem cell memory (P = 0.009, P = 0.08) and naïve (P < 0.001, P = 0.02)] compared to unvaccinated unexposed individuals of CD4 + T and CD8 + T, respectively. However, among HCW and cirrhotic group no difference was noted on central memory and stem cell memory cells on T cells. Patients with liver cirrhosis developed comparable memory T cells after vaccination which can evoke sustainable immune response on reinfection. Therefore, additional vaccine doses may not be necessary for cirrhosis patients.

Study of pattern and outcome of acute poisoning cases at tertiary care hospital in North India.

Introduction: The WHO 2021 data estimate that 2 million lives and 53 million disability-adjusted life-years were lost in 2019 due to exposures to selected chemicals. It is important to know the pattern and outcome of acute poisoning cases for proper planning, prevention and management. Knowing the pattern will also help in designing training modules for primary care physicians to make them aware about newer poisons and their management. Awareness regarding newer poisons consumed is necessary for early identification, initial management and timely referral to higher centres by primary care physicians. This study was performed to see the pattern and outcome of acute poisoning cases in North Indian population and various factors related to outcome. Materials and Methods: This study was conducted in department of medicine of a teaching institute in North India after approval by the Institutional Review Board. Patients admitted in the department during the study and fulfilling the inclusion criteria were enrolled in the study after obtaining consent. Results: A total of 417 patients with poisoning were recruited in the study. Out of 417 patients, majority were males (59.5%). Maximum number of patients were in the age group of 21-30 years (33.8%), and rural population (79.9%) was found to be more affected. Most of the patients were students and private employees. Most common types of poisoning were snakebite (n = 109, 26.1%), organophosphate (n = 49, 11.8%) and aluminium phosphide (n = 39, 9.3%). Out of 417 patients, 349 (83.69%) improved, while 68 (16.3%) expired. Requirement of ventilatory support was most commonly associated with aluminium phosphide poisoning (30.12%) followed by organophosphate poisoning (24.1%). Conclusion: Poisoning was more common in young males and more prevalent in rural population. Pesticides and snakebite were major causes of poisoning. Among suicidal cases, family conflict (problem/altercation with family members/marital discord) was main reason for the consumption of poison. There is need for creation of poison information centre along with separate toxicological units in tertiary care hospitals.

Increased IL-6 Levels and the Upregulation of Iron Regulatory Biomarkers Contribute to the Progression of Japanese Encephalitis Virus Infection's Pathogenesis.

Integrated analysis of iron regulatory biomarkers and inflammatory response could be an important strategy for Japanese encephalitis viral (JEV) infection disease management. In the present study, the inflammatory response was assessed by measuring serum Interleukin-6 (IL-6) levels using ELISA, and the transcription levels of iron homeostasis regulators were analyzed via RT-PCR. Furthermore, inter-individual variation in the transferrin gene was analyzed by PCR-RFLP and their association with clinical symptoms, susceptibility, severity, and outcomes was assessed through binary logistic regression and classification and regression tree (CART) analysis. Our findings revealed elevated levels of IL-6 in serum as well as increased expression of hepcidin (HAMP), transferrin (TF), and transferrin receptor-1 (TFR1) mRNA in JEV infection cases. Moreover, we found a genetic variation in TF (rs4481157) associated with clinical symptoms of meningoencephalitis. CART analysis indicates that individuals with the wild-type TF genotype are more susceptible to moderate JEV infection, while those with the homozygous type are in the high-risk group to develop a severe JEV condition. In summary, the study highlights that JEV infection induces alteration in both IL-6 levels and iron regulatory processes, which play pivotal roles in the development of JEV disease pathologies.

Severe COVID-19-associated hyperinflammatory syndrome versus classic hemophagocytic lymphohistiocytosis: similarities, differences, and the way forward.

The hyperinflammatory immune response in severe COVID-19 infection shares features with secondary hemophagocytic lymphohistiocytosis (sHLH) in the form of fever, cytopenia, elevated inflammatory markers, and high mortality. There are contrasting opinions regarding utility of HLH 2004 or HScore in the diagnosis of severe COVID-19-related hyperinflammatory syndrome (COVID-HIS). This was a retrospective study of 47 patients of severe COVID-19 infection, suspected to have COVID-HIS and 22 patients of sHLH to other illnesses, to evaluate the diagnostic utility and limitations of HLH 2004 and/or HScore in context to COVID-HIS and to also evaluate the utility of Temple criteria for predicting severity and outcome in COVID-HIS. Clinical findings, hematological, and biochemical parameters along with the predictor of mortality were compared between two groups. Only 6.4% (3/47) of cases fulfilled ≥5/8 HLH 2004 criteria and only 40.52% (19/47) of patients showed HScore >169 in COVID-HIS group. 65.9% (31/47) satisfied the Temple criteria in COVID-HIS as compared with 40.9% (9/22) in the non-COVID group (p = 0.04). Serum ferritin (p = 0.02), lactate dehydrogenase (p = 0.02), direct bilirubin (p = 0.02), and C-reactive protein (p = 0.03) were associated with mortality in COVID-HIS. Both HScore and HLH-2004 criteria perform poorly for identifying COVID-HIS. Presence of bone marrow hemophagocytosis may help to identify about one-third of COVID-HIS missed by the Temple Criteria.

T-cell dysfunction as a potential contributing factor in post-COVID-19 mucormycosis.

BACKGROUND: The second wave of COVID-19 in India was followed by large number of mucormycosis cases. Indiscriminate use of immunosuppressive drugs, underlying diseases such as diabetes, cancers, or autoimmune diseases was thought to be the cause. However, the mortality was not as high as that seen in non-COVID mucormycosis. OBJECTIVE: To study the detailed characteristics of T-cells for evaluating the underlying differences in the T-cell immune dysfunction in post-COVID and non-COVID mucor patients. MATERIAL AND METHOD: The study included histopathologically confirmed cases of mucor (13 post-COVID, 13 non-COVID) and 15 healthy individuals (HI). Expression of T-cell activation (CD44, HLADR, CD69, CD38) and exhaustion (CTLA, PD-1, LAG-3 and TIM-3) markers was evaluated by flow cytometry. RESULTS: All cases showed significant depletion of T-cells compared to HI. Both post-COVID and non-COVID groups showed increased activation and exhaustion as compared to HI. Non-COVID mucor group showed significant activation of CD4+ T cells for HLADR and CD38 (p = .025, p = .054) and marked T-cell exhaustion in form of expression of LAG-3 on both CD4+ T and CD8+ T cells in comparison with post-COVID patients (p = .011, p = .036). Additionally, co-expression of PD-1 & LAG-3 and LAG-3 & TIM-3 on CD8+ T cells was statistically significant in non-COVID mucor patients (p = .016, p = .027). CONCLUSION: Immunosuppression in non-COVID mucor showed pronounced exhaustion of T-cells in comparison to post-COVID mucor cases implicating T-cell immune dysfunction is much more severe in non-COVID mucor which are in a state of continuous activation followed by extreme exhaustion leading to poorer outcome.

Acute Methanol Toxicity: Clinical Correlation with Autopsy Findings, a Descriptive Study.

BACKGROUND: Methyl alcohol poisoning or deaths from drinking illegally brewed cheap alcohol which is often spiked with chemicals to increase its potency are frequent in India. Many outbreaks from different parts of the country have been reported from time to time. A total of 11,830 lives were lost between 2006 and 2015 due to the consumption of spurious liquor in the country. The symptoms can range from mild to severe depending upon factors like the amount of exposure and time of presentation. AIMS AND OBJECTIVES: The present study was designed to describe the clinical presentation, management, and outcome of the patients during a recent methanol outbreak that can form a basis for diagnosis and management. This study also highlights the salient autopsy findings and their correlation with clinical features. MATERIALS AND METHODS: It is a retrospective, descriptive study discussing clinical features of patients with methanol intoxication, their outcome, and the clinical correlation with autopsy findings of patients who succumbed to death. The study was conducted at King George's Medical University, Lucknow. The patients were enrolled from a methanol intoxication outbreak in Barabanki district on 28th May 2019 followed by a similar outbreak in Sitapur district two days later. RESULTS: A total of 33 patients were included in this study based on predefined clinical characteristics. The average amount of alcohol consumed was about 223 mL (range: 100-300 mL). The majority of patients had onset of symptoms between 12 and 24 hours. All patients had gastrointestinal symptoms, 97% of patients had visual disturbances, 91% of patients had central nervous system manifestation while frank coma was observed in 15% of patients. Decreased urine output was reported in 6% of patients. About 90% of patients had metabolic acidosis. Out of 33 patients included in this study, 30 patients were discharged in stable condition while two died and one absconded. Autopsy findings revealed marked cerebral edema and hyperemia, hyperemic heart, and congested lungs in all the patients. One patient showed putaminal necrosis which is characteristic of methanol poisoning. Kidneys in two cases were hyperemic and show parenchymal degeneration which co-relates with both patients being anuric. CONCLUSION: Methanol intoxication is a serious problem in developing countries like ours. Timely intervention is an important factor in reducing mortality among these patients. The study highlights the very important fact that methanol intoxication can be managed at the very ground level with minimal resources (as available) if intervened and recognized in time.

Utility of itraconazole and terbinafine in mucormycosis: a proof-of-concept analysis.

An epidemic of mucormycosis followed the second wave of COVID 19 in the state of Uttar Pradesh, India in May 2021. This epidemic, however, had additional challenges to offer in the form of acute shortage of all forms of amphotericin B, posaconazole and isavuconazole. It was, therefore, planned to assess the trends in minimum inhibitory concentration (MIC) of antifungal agents, viz itraconazole and terbinafine, and provide a template for personalized therapy to see whether the results could be translated clinically. This is an observational, single-center study. Samples comprising nasal swab, nasal and paranasal sinus tissue, brain tissue, brain abscess and orbital content, derived from 322 patients from northern India with mucormycosis, of whom 215 were male and 107 were female, were used for analysis. Cultures were identified both by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and conventional methods of identification. Antifungal susceptibility was done for amphotericin B, posaconazole, isavuconazole, itraconazole and terbinafine as per Clinical Laboratory Standard Institute M38-A2. The outcome was identification of the species of mucormycosis and susceptibility to itraconazole and terbinafine besides other primary antifungal agents. Patients or the public were not involved in the design, or conduct, or reporting or in the dissemination plans of our research. Of 322 patients, 203 were culture-positive, of whom 173 were positive by both MALDI-TOF and conventional methods of identification. Final antifungal susceptibility testing was available for 150 patients. The most common Mucorales found to cause this epidemic was Rhizopus oryzae, followed by R. microsporus Amphotericin B, posaconazole and isavuconazole had low MIC values in 98.8% of all Mucorales identified. The MIC of itraconazole was species-dependent. 97.7% of Roryzae had MIC ≤2 µg/mL. However, only 36.5% of Rmicrosporus had MIC ≤2 µg/mL. For terbinafine, 85.2% of R. microsporus had MIC ≤2 µg/mL. We conclude that identification at the species level is required as antifungal susceptibilities seem to be species-dependent. Assessment of the efficacy of itraconazole and terbinafine warrants further studies with clinical assessment and therapeutic drug monitoring as they seem to be potential candidates especially when the primary agents are not available.

A preliminary experience of plasma exchange in liver failure.

INTRODUCTION: Plasma exchange (PLEX) is one of the experimental modalities of treatment for liver failure. We report our experience of PLEX in patients with acute-(ALF) or acute-on-chronic (ACLF) liver failure. METHODS: Hemodynamically stable adult patients with ALF or ACLF, encephalopathy, model for end-stage liver disease (MELD) score ≥ 15, and clinical worsening/no improvement after 72-h of inpatient care were included. PLEX cycles repeated every 48 h, each of 2.5-4.0 h duration with 1-1.5 times of estimated plasma volume, were given. PLEX cycle was repeated till either of the end-points were achieved (i) MELD < 20 for 48 h or reaches below the baseline, whichever is lower, (ii) completed three PLEX cycles, (iii) hemodynamic instability, (iv) or outcome achieved. Outcome of interest was categorized as favorable (discharged in stable condition) or unfavorable (death or discharge in moribund condition). Data are expressed as median (interquartile range). RESULTS: Sixteen patients (age 35 [27-48] years; male 8; ALF 5, ACLF 11; MELD 33 [27-37]; CLIF-SOFA 10 [8.5-12]) were included. Participants received 2 (1-3) cycles of PLEX during 13 (11-25) days of hospitalization. Overall, serum bilirubin, INR, creatinine, MELD, and CLIF-SOFA scores were significantly improved after PLEX. Five patients (5/16, 31%) had complete resolution of HE. Eight patients (50%) had a favorable outcome. Those with favorable outcome had significant improvement in serum bilirubin, INR, and CLIF-SOFA scores as compared to those with unfavorable outcome. CONCLUSION: PLEX may be effective in patients with ALF or ACLF. More data are needed to establish its role in the management of liver failure.

Study of central aortic blood pressure in hypertensive patients & its relation with blood pressure-lowering drugs.

Background & objectives: In clinical settings, peripheral blood pressure (PBP) is measured routinely. It is thought that central blood pressure (CBP) which reflects aortic BP, may be more predictive of outcomes in specific populations. Hence, this study was carried out to measure CBP in patients with hypertension and to see the effect of antihypertensive drugs on CBP. Methods: This cross-sectional study was conducted on 134 hypertensive patients and 134 normotensive healthy individuals as controls. Peripheral BPs and CBPs were measured of all patients and controls. The data were correlated and the effect of antihypertensive drugs on CBP was also evaluated. Results: Of the 134 hypertensive patients, 44 (32.84%) were newly diagnosed and the rest 90 (67.16%) had a history of hypertension and were on treatment. Of these 90 patients on treatment, 37 (41.11%) had uncontrolled peripheral BP and 53 (58.89%) had normal peripheral BP. Of the 134 hypertensive patients, 45 (33.58%) had controlled CBP. In 90 patients, who were on antihypertensive treatment, 45 (50%) had controlled CBP and 45 (50%) had uncontrolled CBP. Patients on calcium channel blockers (CCBs) had better control of CBP. Interpretation & conclusions: Hypertension is diagnosed mainly by measuring peripheral BP. CBP, which correlates better with the incidence of cardiovascular events, is not routinely measured. Patients with a history of hypertension and on treatment had normal office peripheral BP, but a few of them had high CBP and may require modification in treatment for control of CBP. Control of CBP was better in patients taking CCB.

COVID-19 associated mucormycosis: Staging and management recommendations (Report of a multi-disciplinary expert committee).

Even before the onslaught of COVID-19 pandemic could settle, the unprecedented rise in cases with COVID-19 associated mucormycosis pushed the medical health to the fringe. Hyperglycaemia and corticosteroids appear to be the most consistent associations leading to the commonest manifestation of mucormycosis, Rhino-Orbito-Cerebral Mucormycosis. To address challenges right from categorisation and staging of the disease to the management of relentless progression, a multi-disciplinary expert committee was formed to handle the task in an evidence-based format to enforce best practices. The report of the committee on one hand attempts to succinctly present the currently available evidence while at the other also attempts to bridge the evidence-deficient gaps with the specialty-specific virtuosity of experts.

COVID-19-associated Guillain-Barre syndrome: Postinfectious alone or neuroinvasive too?

Coronavirus disease 2019 (COVID-19) has been shown to be associated with a lot of neurological complications, of whom Guillain-Barre syndrome (GBS) is an important post-infectious consequentiality. More than 220 patients with GBS have been reported thus far. We intend to share our experience with five patients of GBS where one of them had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the cerebrospinal fluid (CSF). This is the first-ever report demonstrating the presence of SARS-CoV-2 in the CSF of an adult patient; a similar occurrence has recently been described in a pediatric patient. We wish to emphasize the fact that commonly GBS occurs as a result of a post-infectious process but in a few cases where the symptoms of COVID-19 and GBS occur concurrently, corresponding to the viremic phase, separate pathogenesis needs to be thought of. This para-infectious nature is exemplified by the presence of virus in the cerebrospinal fluid of one of our patients. We review the neuroinvasive potential of SARS-Cov-2 in this regard and draw parallels with Cytomegalovirus, Zika virus, and Human Immunodeficiency virus-associated occurrences of GBS.

Hemophagocytic histiocytosis in severe SARS-CoV-2 infection: A bone marrow study.

INTRODUCTION: The clinical and laboratory features of severe COVID-19 infection overlap with those of hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory disorder often associated with several viral infections. The clinical syndrome of HLH encompasses fever, organomegaly, cytopenias, hyperferritinemia, hypertriglyceridemia, raised transaminases, hypofibrinogenemia, absent natural killer (NK) cell activity, increased soluble CD25 and hemophagocytic lymphohistiocytosis in bone marrow, spleen, and lymph nodes. METHODS: We analyzed clinicopathological and laboratory features of thirteen patients with severe COVID-19 infection suspected to have HLH and found to have hemophagocytic histiocytosis on bone marrow examination (BME). RESULTS: Five of thirteen (38.46%) patients fulfilled five of eight HLH 2004 criteria and/or had a H-score ≥169. Three (23.08%) satisfied four of eight and remainder five (38.46%) satisfied three of eight HLH 2004 criteria. Fever, raised serum ferritin (13/13, 100%), transaminases (9/13, 69.23%), triglycerides (4/13, 30.76%), cytopenias (5/13, 38.46%), hypofibrinogenemia (2/13, 15.38%), and organomegaly (1/13, 7.69%) were observed in our patients. BME showed hemophagocytic histiocytosis without lymphocytosis in all. Contrary to HLH, lymphocytopenia (11/13, 84.61%), leukocytosis (7/13, 53.84%), neutrophilia (7/13, 53.84%), and hyperfibrinogenemia (7/13, 53.84%) were observed. Serum CRP, LDH, and plasma D-dimer were elevated in all, while serum albumin was decreased in 12 of 13 (92.3%) patients. Five patients recovered with high-dose pulsed corticosteroid therapy. CONCLUSION: The immune response associated with severe COVID-19 infection is similar to HLH with few differences. HLH should be suspected in severe COVID-19 infection although all patients may not fulfill required HLH diagnostic criteria. BME should be done in suspected cases so that appropriate therapy may be initiated early.

Complicated case of COVID-19 disease with overlapping features of thrombotic thrombocytopenic purpura and haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis has been reported as an uncommon complication of severe COVID-19 disease while thrombotic thrombocytopenic purpura has been rarely reported. Here, we are reporting a 21-year-old man who developed a combination of these complications during the hospital stay in the post-COVID-19 recovery period. He presented with fever and bilateral COVID-19-related pneumonia requiring invasive ventilation. His hospital course was complicated by the development of pneumothorax, ventilator-associated pneumonia, thrombotic thrombocytopenic purpura and haemophagocytic lymphohistiocytosis. He received remdesivir, IVIG, steroid, fresh frozen plasma and supportive care but had a fatal outcome.

A Phase II Safety and Efficacy Study on Prognosis of Moderate Pneumonia in Coronavirus Disease 2019 Patients With Regular Intravenous Immunoglobulin Therapy.

BACKGROUND: Currently, there is no specific drug for the treatment of coronavirus disease 2019 (COVID-19). Therapeutic benefits of intravenous immunoglobulin (IVIG) have been demonstrated in wide range of diseases. The present study is conducted to evaluate the safety and efficacy of IVIG in the treatment of COVID-19 patients with moderate pneumonia. METHODS: An open-label, multicenter, comparative, randomized study was conducted on COVID-19 patients with moderate pneumonia. One hundred eligible patients were randomized in 1:1 ratio either to receive IVIG + standard of care (SOC) or SOC. RESULTS: Duration of hospital stay was significantly shorter in the IVIG group compared with that of SOC alone (7.7 vs 17.5 days). Duration for normalization of body temperature, oxygen saturation, and mechanical ventilation were significantly shorter in IVIG compared with SOC. Percentages of patients on mechanical ventilation in 2 groups were not significantly different (24% vs 38%). Median time to reverse-transcription polymerase chain reaction negativity was significantly shorter with IVIG than SOC (7 vs 18 days). There were only mild to moderate adverse events in both groups except for 1 patient (2%), who died in SOC. CONCLUSIONS: Intravenous immunoglobulin was safe and efficacious as an adjuvant with other antiviral drugs in the treatment of COVID-19.

COVID-19: benefits and risks of passive immunotherapeutics.

Passive immunotherapeutics (PITs), including convalescent plasma, serum, or hyperimmune immunoglobulin, have been of clinical importance during sudden outbreaks since the early twentieth century for the treatment of viral diseases such as severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and swine flu (H1N1). With the recent SARS-CoV-2 pandemic, wherein effective antivirals and vaccines are still lacking, an interest in convalescent plasma therapy as a lifesaving option has resurfaced due to its capacity for antigenic neutralization and reducing viremia. This review summarizes convalescent blood products (CBPs) in terms of current technologies and the shortcomings related to the collection, manufacture, pathogen inactivation, and banking of CBPs, with a specific focus on their plausible applications, benefits, and risks in the COVID-19 pandemic.

Global Perspective of Novel Therapeutic Strategies for the Management of NeuroAIDS.

Among Human immunodeficiency virus (HIV) infected individuals, around two-thirds of patients present with neuroAIDS, where HIV-associated neurocognitive disorders (HAND), and HIV-associated dementia (HAD) are the most prevailing neurological complications. The neuropathology of neuroAIDS can be characterized by the presence of HIV infected macrophages and microglia in the brain, with the formation of multinucleated giant cells. Global predominant subtypes of HIV-1 clade B and C infections influence the differential effect of immune and neuronal dysfunctions, leading to clade-specific clinical variation in neuroAIDS patient cohorts. Highly active antiretroviral therapy (HAART) enhances the survival rate among AIDS patients, but due to the inability to cross the Blood-Brain-Barrier (BBB), incidence of neuroAIDS during disease progression may be envisaged. The complex structure of blood-brain-barrier, and poor pharmacokinetic profile coupled with weak bio-distribution of antiretroviral drugs, are the principle barriers for the treatment of neuroAIDS. In the combined antiretroviral therapy (cART) era, the frequency of HAD has decreased; however the incidence of asymptomatic neurocognitive impairment (ANI) and minor neurocognitive disorder (MND) remains consistent. Therefore, several effective novel nanotechnology based therapeutic approaches have been developed to improve the availability of antiretroviral drugs in the brain for the management of neuroAIDS.