Acquired Immunodeficiency Disease Research Articles

Reactive Neutrophilic Dermatoses in Adult-Onset Immunodeficiency due to Interferon-Gamma Autoantibody and Their Associated Factors

Background: Adult-onset immunodeficiency (AOID) due to interferon-gamma autoantibody is a rare, acquired immunodeficiency disease. Reactive neutrophilic dermatoses (RND), predominantly Sweet syndrome (SS), and generalized pustular eruption have been reported repeatedly. Objectives: The aims of this study were to describe the cutaneous manifestations in AOID patients and determine the incidence of RND and associated factors using a larger population size than have been previously reported. Methods: A retrospective chart review of all confirmed AOID cases in Chiang Mai University Hospital from January 2006 to June 2020 was conducted. The demographics and characteristics of RND including type, onset, and laboratory information in every episode of cutaneous manifestations were collected. Generalized estimating equations of binary logistic regression were used to determine the indicators of RND. Results: A total of 146 patients with confirmed AOID were identified. Of these, 57 cases (39%) developed at least one episode of RND. Thirteen cases (23%) of the patients experienced RND twice during the follow-up period. All recurrence of RND displayed the same cutaneous phenotype, with the exception of 2 cases who had both SS and generalized pustular eruption. Finally, 49 episodes of SS and 22 episodes of generalized pustular eruption were included in the analysis. All patients with RND had concomitant active opportunistic infections, of which most were non-tuberculous mycobacterium (NTM) infection. NTM infection (prevalence odds ratio [POR] 2.87), lymphadenopathy (POR 3.30) as well as lower serum alkaline phosphatase (ALP) level (POR 0.71 for every 100-unit increment in ALP) were found to be significantly associated with RND occurrence. Conclusions: 39% of our AOID patients experienced RND once during the course of the disease. Notable factors associated with RND occurrence were concomitant NTM infection, lymphadenopathy, and lower level of ALP.

Utilization of antiviral for HIV prevention

Acquired immunodeficiency disease syndrome (AIDS) and AIDS-related illnesses continue to cause a public and economic burden on any given community. Different preventive strategies have been reported, which vary in their effectiveness and safety to limit human immunodeficiency virus (HIV) transmission, the causative virus of AIDS. Antiretroviral therapy (ART) is the main agent used for HIV treatment, and it has been used as a prevention method, or prophylaxis, to prevent HIV transmission. This review was conducted to evaluate clinical trials, and updated recommendations for preventing HIV infection for individuals at risk using ART. We reviewed the literature, and six studies responded to our inclusion criteria. Most of the recent studies that used ART seemed effective in preventing HIV infection among seronegative individuals. Further studies on a larger and different population are recommended to ensure the best preventive methods against HIV.

The Role of CD4+CD8+ T Cells in HIV Infection With Tuberculosis

BackgroundTuberculosis (TB) is an important opportunistic infection in acquired immunodeficiency diseases (AIDS). Although the frequency of CD4+CD8+ double-positive (DP) T cells has been observed to increase in pathological conditions, their role (phenotypic and functional) is poorly described, especially in human immunodeficiency virus (HIV) infection with TB (HIV/TB (HT) coinfection).MethodsThe percentage and phenotypic and functional properties of peripheral blood DP T cells in patients with HT coinfection in comparison to uninfected controls and to patients with HIV or TB mono-infection were analyzed by direct intracellular cytokine staining (ICS).ResultsTotal and CD4lowCD8high DP T cells were significantly increased in patients with both HIV and TB mono-infection, especially in patients with HT coinfection. Compared with healthy controls (HCs), the percentage of DP T cells expressing chemokine receptor 5 (CCR5) in patients with HT coinfection was significantly higher. Compared with HCs and patients with TB, a lower percentage of tumor necrosis factor α (TNF-α) secreting DP T cells and a higher percentage of granzyme A-secreting DP T cells were observed in patients with HIV mono-infection and HT coinfection, respectively. In addition, DP T cells expressed more cytolytic markers (granzyme A and perforin) than CD4+ T cells, but similarly to CD8+ T cells in patients with HT coinfection.ConclusionsOur data suggested that HT coinfection resulted in a marked increase in DP T cells, especially the CD4lowCD8high subpopulation. DP T cells may be susceptible to HT coinfection, and have the same cytotoxic function as CD8+ T cells.

COVID-19 Vaccines for HIV-Infected Patients.

Nearly 40 years have passed since the initial cases of infection with the human mmunodeficiency virus (HIV) were identified as a new disease entity and the cause of acquired immunodeficiency disease (AIDS). This virus, unlike any other, is capable of causing severe suppression of our adaptive immune defense mechanisms by directly infecting and destroying helper T cells leading to increased susceptibility to a wide variety of microbial pathogens, especially those considered to be intracellular or opportunistic. After T cells are infected, HIV reproduces itself via a somewhat unique mechanism involving various metabolic steps, which includes the use of a reverse transcriptase enzyme that enables the viral RNA to produce copies of its complementary DNA. Subsequent physiologic steps lead to the production of new virus progeny and the eventual death of the invaded T cell. Fortunately, both serologic and molecular tests (such as PCR) can be used to confirm the diagnosis of an HIV infection. In the wake of the current COVID-19 pandemic, it appears that people living with HIV/AIDS are equally or slightly more susceptible to the etiologic agent, SARS-CoV-2, than the general population having intact immune systems, but they may have more serious outcomes. Limited clinical trials have also shown that the currently available COVID-19 vaccines are both safe and effective in affording protection to HIV/AIDS patients. In this review, we further explore the unique dynamic of HIV/AIDS in the context of the worldwide COVID-19 pandemic and the implementation of vaccines as a protective measure against COVID-19, as well as what immune parameters and safeguards should be monitored in this immunocompromised group following vaccination.

Pneumocystis Pneumonia: Immunity, Vaccines, and Treatments.

For individuals who are immunocompromised, the opportunistic fungal pathogen Pneumocystis jirovecii is capable of causing life-threatening pneumonia as the causative agent of Pneumocystis pneumonia (PCP). PCP remains an acquired immunodeficiency disease (AIDS)-defining illness in the era of antiretroviral therapy. In addition, a rise in non-human immunodeficiency virus (HIV)-associated PCP has been observed due to increased usage of immunosuppressive and immunomodulating therapies. With the persistence of HIV-related PCP cases and associated morbidity and mortality, as well as difficult to diagnose non-HIV-related PCP cases, an improvement over current treatment and prevention standards is warranted. Current therapeutic strategies have primarily focused on the administration of trimethoprim-sulfamethoxazole, which is effective at disease prevention. However, current treatments are inadequate for treatment of PCP and prevention of PCP-related death, as evidenced by consistently high mortality rates for those hospitalized with PCP. There are no vaccines in clinical trials for the prevention of PCP, and significant obstacles exist that have slowed development, including host range specificity, and the inability to culture Pneumocystis spp. in vitro. In this review, we overview the immune response to Pneumocystis spp., and discuss current progress on novel vaccines and therapies currently in the preclinical and clinical pipeline.

An appraisal on quality of life in AIDS patient

Quality of life is the expectation of the individual or society for a good life which outline both positive and negative features of life. Acquired immunodeficiency disease is caused by human retrovirus which was considered as a fat illness before the introduction of proper treatment. Symptoms of the disease include flu like illness, skin rash, sore throat, opportunistic infections, enlarged lymohnodes in necks and so on. According to Who ,since the beginning of pandemic 76 million people have been infected with hiv virus and about 33 million deaths has been reported. At the end of 2019 about 38.0 million people were living with the disease globally. Antiretroviral drugs are used for the treatment of human immune deficiency virus. The review paper was prepared by referring review and research papers from research gate, pubmed, goggle scholar, science direct and search was based on key words such as AIDS, HAART, Quality of life in Aids patients. Aids was considered as a fatal illness till the introduction of proper treatment regimen. The morbidity, mortality and disease severity was reduced to a great extent by antiretroviral drugs. Quality of life was also seen to be improved in patients. Social support has a positive impact on quality of life. Factors like depression, emotional stress, unemployment, suicidal ideation affect the quality of life in AIDS patients.

Epidemiological Determinants of Acute Respiratory Syndrome Coronavirus-2 Disease Pandemic and The Role of the Bacille-Calmette-Guerin Vaccine in Reducing Morbidity and Mortality

This study analyzed the determinants of morbidity, mortality, and case fatality rate (CFR) of the ongoing pandemic of severe acute respiratory syndrome coronavirus-2 disease 2019 (COVID-19). Data for 210 countries and territories available in public domains were analyzed in relation to mandatory vaccination with Bacille-Calmette-Guerin (BCG), population density, median age of the country population, health care expenditure per capita, life expectancy at birth, healthy life expectancy, literacy rate, per capita gross domestic production adjusted to purchasing power (PPP), burden of tuberculosis (TB), acquired immunodeficiency disease caused by human immunodeficiency virus (HIV-AIDS), malaria, cardiovascular disease (CVD), neoplasm, diabetes, deaths due to energy-protein (food) deficiency (EPD), and per capita government spending on safe water and sanitation. Mandatory BCG vaccination showed a highly significant (p<0.0001) negative correlation with COVID-19 morbidity (r = -0.62) and mortality (r = -0.58) rates, but no significant correlation with CFR. The median age of the nation showed a significant (p<0.0001) positive correlation with COVID-19 morbidity (r= 0.40) and mortality (r = 0.34) rates, but no significant correlation with CFR. The pandemic resulted in higher morbidity (r= 0.47, p<0.0001) and mortality (r= 0.25, p = 0.01) rates in countries with a higher PPP than in those with a lower PPP. COVID-19 CFR and morbidity and mortality rates showed no significant correlation with population density, the burden of malaria or diabetes, or the level of spending on safe water and sanitation. Only the burden of TB showed a positive correlation with CFR (r = 0.17, p = 0.05). However, COVID-19 morbidity showed a significant (p ≤0.05) negative correlation with the burden of TB, HIV-AIDS, CVD, and EPD. Mortality and morbidity in COVID-19 patients showed a positive correlation with per capita health expenditure, life expectancy, the burden of neoplasia, and PPP.

Selected genes of Human herpesvirus-8 associated Kaposi's sarcoma among patients with Human Immunodeficiency Virus-1 and Acquired Immunodeficiency Disease Syndrome.

IntroductionKaposi's sarcoma (KS) is a kind of cancer that causes flat or raised lesions containing Human herpes virus 8 (HHV8). The KS lesions are common among immunosuppressed HIV patients. Highly Active Antiretroviral (HHART) treats and prevents the development of KS. The objective of this study was to determine the presence of K1 and K15 (predominant alleles) genes in Kaposi's sarcoma-associated herpes virus (KSHV) among immunosuppressed patients due to HIV-1.MethodsThis was a cross-sectional descriptive study where consecutive sampling technique was adopted to pick archived tissue blocks from the Thematic Unit of Anatomic Pathology, Department of Human Pathology, College of Health Sciences, University of Nairobi and Department of Laboratory Medicine, Histology Section, Kenyatta National Hospital.ResultsUpon staining 81 tissue blocks with H & E, 84% (68/81) were diagnosed as KS and 16% (13/81) as KS-like. The K1 and K15 (P) genes were both detected at 88.9% (72/81) in the tissue blocks, with 95.8% (69/72) detection from KS and 4.2% (3/72) from the KS-like.ConclusionThe K1 and K15 (P) genes of KSHV were present among the immunosuppressed patients with Human Immunodeficiency Virus (HIV)-1. It is important to carry out K1 and K15 (P) genes detection on tissues that are diagnosed as KS or KS-like by histology technique.

Retroviruses and reproduction revisited

Thanks to effective anti-HIV medications, deaths from acquired immunodeficiency disease (AIDS) have plummeted, although the incidence of new HIV infections has decreased little, approximately 36,000 annually in the USA. The CDC estimates 1.1 million persons, mostly men, are living with HIV in the USA, with approximately 14% unaware they are infected. Since the global blood supply is essentially free of HIV today, infected semen is fueling the pandemic (88% of new infections in the USA), with needle sharing among IV drug abusers (7% of new US infections) and female to male transmission (5% of new infections) accounting for the balance. In spite of the importance to disease prevention and strategies for safe conception, semen transmission of HIV is not well understood. Because anti-HIV therapy does not eliminate HIV from semen, the Centers for Disease Control (CDC) for the past 25 years has espoused condom use as the safest approach to prevent HIV transmission, as well as other sexually transmitted diseases. A few months ago, however, an MMWR was circulated by the CDC that suggested condomless sex might be safe if the HIV-infected partner’s medications achieved an undetectable viral load in his blood. This new opinion was based on reports by three teams of investigators cited in the MMWR: “All three studies observed no HIV transmission to the uninfected partner while the partner with HIV was virologically suppressed with ART.” Unfortunately, this CDC statement does not fully describe the data presented in the studies, and abandoning condom use puts uninfected partners, including women seeking to conceive, at risk for infection by HIV and other STDs.

Differentiation and Function of Follicular CD8 T Cells During Human Immunodeficiency Virus Infection.

The combination antiretroviral therapeutic (cART) regime effectively suppresses human immunodeficiency virus (HIV) replication and prevents progression to acquired immunodeficiency diseases. However, cART is not a cure, and viral rebound will occur immediately after treatment is interrupted largely due to the long-term presence of an HIV reservoir that is composed of latently infected target cells that maintain a quiescent state or persistently produce infectious viruses. CD4 T cells that reside in B-cell follicles within lymphoid tissues, called follicular helper T cells (TFH), have been identified as a major HIV reservoir. Due to their specialized anatomical structure, HIV-specific CD8 T cells are largely insulated from this TFH reservoir. It is increasingly clear that the elimination of TFH reservoirs is a key step toward a functional cure for HIV infection. Recently, several studies have suggested that a fraction of HIV-specific CD8 T cells can differentiate into a CXCR5-expressing subset, which are able to migrate into B-cell follicles and inhibit viral replication. In this review, we discuss the differentiation and functions of this newly identified CD8 T-cell subset and propose potential strategies for purging TFH HIV reservoirs by utilizing this unique population.

C-X-C RECEPTOR 4 {CXCR4} METASTASIS KANKER PAYUDARA

The chemokine receptors CXCR4 (chemokine C-X-C motif receptor 4) and its ligand (stromal derived factor-1/SDF-1 or chemokinemotif ligand 12/CXCL12) play an important role in cancer invasion and metastasis. The spread of breast cancer follows a nonrandommetastatic pattern typically involving spread of tumor to regional lymph nodes, lung, liver, and/or bone marrow. The ligand for CXCR4,SDF-1/CXCL12, is highly expressed by stromal fibroblasts within these tissues. The chemokine receptors CXCR4 is structurally related tochemokine receptor belonging to the superfamily of the seven transmembrane G-protein coupled receptors. In contrast to normal breasttissue, breast cancer cells typically express high levels of functional CXCR4 receptors that can direct chemotaxis and invasive responses.Expression of SDF-1/CXCL-12 in turn, promotes the progression of breast cancer by directly enhancing tumor-cell growth and by recruitingendothelial progenitor cells that are required for tumor angiogenesis. High-level expression of CXCR4 on neoplastic cells is associated withrelatively poor overall survival and bad prognosis in patients with breast cancer. The promising results in the preclinical tumor modelsindicate that CXCR4 antagonists may have to reduce the spread of cancer that is called anti tumor activity in patients with breast cancer.The chemokine receptors CXCR4 antagonists, although initially developed for treatment of acquired immunodeficiency diseases syndrome(AIDS), actually may become effective agents as a molecular targeted therapy for breast cancer.

Pneumocystis pneumonia as the first presentation of acquired immunodeficiency disease

Pneumocystis pneumonia (PCP) is a challenging disease faced in immunodeficiency diseases. PCP became important when human immunodeficiency virus (HIV) epidemic in the world. Due to the increasing prevalence of the disease, especially people with acquired immunodeficiency disease (AIDs), here, we report a patient with AIDs and PCP. A 42-year-old woman living in a care center has been presented with a 2-month history of fever, chills, rough cough, and 6 kg weight loss. She was admitted to our hospital due to nonresponse to the outpatient treatments. The result of smear and staining was positive for PCP and patient was treated with trimethoprim-sulfamethoxazole. After 1 week, respiratory symptoms and fever has been getting better. No specific cause was determined for pancytopenia and for the second time viral markers was tested, and HIV mix reactive by Eliza was positive this time. Hence, she has been introduced to the health center to get treatment. Negative HIV test does not rule out the disease. In patients with long-term respiratory infections with leukopenia and failure to respond to common antibiotics, checking PCP is needed.

Mycological Profile of Sputum of HIV Positive Patients with Lower Respiratory Tract Infection and its Correlation with CD4+ T Lymphocyte Count.

Fungal respiratory infections are important cause of mortality and morbidity among HIV positive individuals. They account for up to 70% of illness in Acquired Immunodeficiency Disease Syndrome cases (AIDS). The range of illness varies from asymptomatic mucosal candidiasis to overwhelming disseminated infections. In these patients dissemination of fungus leads to very serious outcomes hence, it is important to have the knowledge of prevailing profile of fungus causing infections, so that it can be treated at the onset. Low CD4+ T lymphocyte count is an excellent indicator of decreased immunity and can also be helpful to predict opportunistic fungal respiratory infections and other complications. To define the fungal aetiology of lower respiratory tract infections in HIV positive patients and to correlate the occurrence of different fungi with CD4+ T lymphocyte count. This was a cross sectional study conducted between May 2014 to April 2015, on 180 treatment naive HIV seropositive patients with lower respiratory tract infections attending the Integrated Counselling and Testing Centre, SMS Medical College, Jaipur, Rajasthan. Early morning expectorated and induced sputum samples were collected and processed for isolation and identification of fungal species. CD4+ T lymphocyte count estimation was done by BD FACS Calibur. Fungal species were isolated from 155 (86.1%) patients. The most common isolate was Candida albicans (31.7%), followed by Aspergillus niger (17.7%) and Aspergillus flavus (10%). The fungal species were most commonly isolated from patients with CD4+ T lymphocyte cell less than 200 cells/μl. Fungal infections were seen in 86.1% of HIV positive patients with lower respiratory tract infections hence, high level of clinical suspicion for fungal aetiology of respiratory infections in HIV positive patients should be kept in mind.

Ocular syphilis in patients with Human Immunodeficiency Virus infection

As Acquired Immunodeficiency Disease (AIDS) turns thirty-years old, much progress has been made. 56,000 new cases of the Human Immunodeficiency Virus (HIV) infection are expected in Americans this year. At least half or more will be in African Americans. Reports of the association between syphilis and HIV infection are well documented. We present a case of bilateral optic neuritis and panuveitis as the initial presentation in a previously undiagnosed patient with human immunodeficiency virus (HIV) and syphilis.

Key role of human leukocyte antigen in modulating human immunodeficiency virus progression: An overview of the possible applications.

Host and viral factors deeply influence the human immunodeficiency virus (HIV) disease progression. Among them human leukocyte antigen (HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class I molecules are recognized by CD8(+) T-cells and natural killers (NK) cells towards the interaction with T cell receptor (TCR) and Killer Immunoglobulin Receptor (KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA class I peptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLA-receptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.

Perceptions and outlook towards HIV/AIDS among reproductive age group of urban slum population

Background: Acquired Immunodeficiency Disease Syndrome (AIDS) has evolved into a pandemic affecting millions of people worldwide. The global HIV/AIDS epidemic has had a major detrimental impact on high risk group and general population leading to morbidity and mortality. Aims & Objective: To assess the perceptions and attitude among reproductive age group of urban slum population towards HIV/AIDS. Materials and Methods: This was a Community Based Cross Sectional Study carried out in the urban slums, field practice area of Community Medicine attached to a tertiary care hospital. The study was conducted by interviewing general population in the reproductive age group for four months in the urban slums using pre-designed and pre-tested proforma. Results: A total of 188 were interviewed. Out of which 48.94% were more than 35 years of age. 51.59% were housewives and belonged to middle class families. 80.85% were aware about sexual transmission and 67.18% opined that it can be prevented by using condoms. Literates were more aware about HIV/AIDS, when compared to illiterates, which was statistically significant (p<0.05). However, majority of them lacked the knowledge of risks associated with breastfeeding by HIV positive mothers. Conclusion: Thus, impetus has to be laid upon awareness and counselling regarding HIV/AIDS at all levels of health care. Integrated Counselling Testing Centres (ICTC) should be made available at all the hospitals, so as to heighten the knowledge of facilities available at a negligible cost, to lead safer and better life.

Glucose Phosphate Isomerase Deficiency In 2 Patients With Novel Mutations Presenting As Severe Neurologic Abnormalities and Transfusion Dependent Hemolytic Anemia

▪ IntroductionGlucose phosphate isomerase (GPI) deficiency is the third most common red cell enzymopathy. GPI is an enzyme that reversibly catalyzes the conversion of glucose-6-phosphate into fructose 6-phosphate in the second step of glycolysis. Patients afflicted by GPI deficiency have chronic hemolysis and may also suffer from acute hemolytic crises. There are 184 known mutations of the GPI gene and to date, a neurological deficit is found in only five patients and only two of these have been characterized at a molecular level. We report 2 patients with previously unknown mutations of the GPI gene associated with, severe neurologic abnormalities and hemolytic anemia. Case 1He was born at 38 weeks gestation; marked pallor and hepatosplenomegaly were noted at birth. The bilirubin was elevated at birth (indirect 7.5 mg/dl and direct 2.2mg/dl) requiring phototherapy. He has transfusion dependent anemia since birth. Enzymes studied were performed which showed GPI levels of 2.02 EU/gm hb ( normal range 16.3-24.7 ) and elevated glucose 6 phosphate dehydrogenase , pyruvate kinase and hexokinase. The pyrimidine 5'-nucleotidase screen was normal. In his subsequent course, he started to have seizures at 6 months of age, refractory to anticonvulsant therapy. He has severe hypotonia and global developmental delay. Magnetic resonance imaging of the brain showed generalized cerebral atrophy with no evidence of kernicterus. Case 2He was noted to have anemia and marked hepatosplenomegaly at birth. He required exchange transfusions and phototherapy in the neonatal period. He has subsequently suffered from lifelong transfusion-dependent hemolytic anemia. He also suffers from developmental delay, ataxia, spasticity, and seizures. Of note, MRI did not exhibit evidence of kernicterus.Table. Mutations of the GPI gene in both the patientsMutation : Change in amino acid and locationLocation of amino acid in GPI crystal structureCarrier parentCASE 1Histidine to arginine at codon 191 (H191R)located in alpha helix tenFatherGlycine to tryptophan at codon 381 (G381W)located in beta sheet fourMotherCASE 2Arginine to glutamine at codon 104 (R104Q)boundary of alpha helix sevenMotherLeucine to phenylalanine at codon 297 (L297F).located in alpha helix fifteenFatherThe mutations were predicted to be pathogenic (probably damaging) by PolyPhen. Both these mutations were in a highly conserved residue. Genetic probe for preimplantation diagnosis is being used for selection of an embryo which is does not have GPI deficiency and is also a potential HLA match with the hope of undergoing hematopoietic stem cell transplantation to avoid the complications of chronic transfusions and iron overload. DiscussionGPI has many functions. In dimeric form, it exhibits its catalytic function. In monomeric form, it acts as a neurotrophic growth factor, neuroleukin, which in vitro promotes survival of neurons. Abnormalities in neuroleukin have been found in motor neuron disease and in patients with central nervous system abnormalities in patients with acquired immunodeficiency disease. These effects of GPI/neuroleukin and relative deficiency in brain and neurons of this protein may explain the neurologic presentation. Decreased phosphatide phosphatase 1 activity, a lipogeneic enzyme due to mTOR activation by accumulated glucose-6-phosphate has been suggested to contribute to the neurologic symptoms. Why some of these mutation are associated with neurologic deficits while most others are not is not known. It has been speculated that the mutations which affect the folding may cause altered structure and function causing neurologic symptoms as well as hemolytic anemia while mutations affecting the catalytic site presents only as hemolytic anemia without neurologic symptoms. Disclosures:No relevant conflicts of interest to declare.

Closing the door to human immunodeficiency virus

The pandemic of human immunodeficiency virus type one (HIV-1), the major etiologic agent of acquired immunodeficiency disease (AIDS), has led to over 33 million people living with the virus, among which 18 million are women and children. Until now, there is neither an effective vaccine nor a therapeutic cure despite over 30 years of efforts. Although the Thai RV144 vaccine trial has demonstrated an efficacy of 31.2%, an effective vaccine will likely rely on a breakthrough discovery of immunogens to elicit broadly reactive neutralizing antibodies, which may take years to achieve. Therefore, there is an urgency of exploring other prophylactic strategies. Recently, antiretroviral treatment as prevention is an exciting area of progress in HIV-1 research. Although effective, the implementation of such strategy faces great financial, political and social challenges in heavily affected regions such as developing countries where drug resistant viruses have already been found with growing incidence. Activating latently infected cells for therapeutic cure is another area of challenge. Since it is greatly difficult to eradicate HIV-1 after the establishment of viral latency, it is necessary to investigate strategies that may close the door to HIV-1. Here, we review studies on non-vaccine strategies in targeting viral entry, which may have critical implications for HIV-1 prevention.

Association of Hematological Profile of Human Immunodeficiency Virus-Positive Patients with Clinicoimmunologic Stages of the Disease

Aim:This work was carried out to study the hematologic profile of human immunodeficiency virus (HIV)-positive patients and its association with the clinicoimmunologic stage of the disease.Materials and Methods:A total of 187 patients with HIV, whether symptomatic or asymptomatic, diagnosed by enzyme-linked immunosorbent assay (ELISA) method according to the National AIDS Control Organization (NACO) guidelines were included in this study. Patients in the study population were divided into two groups: (1) Group A (antiretroviral therapy (ART) included patients receiving ART [ART-Y]) and (2) Group B included treatment naïve patients (ART-N). The patients were tested for hemoglobin (Hb), total red blood cells (RBC) count, RBC indices, reticulocyte count, packed cell volume (PCV), total lymphocyte counts(TLC), differential leukocyte counts (DLC), platelet count, and erythrocyte sedimentation rate (ESR). Cut-off values were determined as Hb < 10 g/dl, platelet count < 1.5 lakh/cumm, and TLC < 4,000/cumm. The group or categorical data were tested for statistical significance using Chi-square test and Z-test. The difference was reported as significant if P < 0.05.Results:(1) Anemia (predominantly normocytic normochromic) was prevalent in 40.1%, with slightly higher prevalence in those not receiving ART. It occurred with high frequency in patients with immunological (42.05%) and clinical acquired immunodeficiency disease syndrome (AIDS) (70.58%) compared with those who had an asymptomatic HIV infection with CD4 > 200/μl (28.57%). Patients on zidovudine (AZT) therapy had 34.6% anemia with increased mean corpuscular volume (MCV). (2) Thrombocytopenia was seen in 3.74% patients (higher percentage in untreated patients). (3) Leucopenia was observed in 5.88% in ART-Y (Group A) and 8.14% in ART-N (Group B) patients. (4) Pancytopenia was found in 1.6% patients.

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Case Reports: Patients with Acquired Immunodeficiency Disease Syndrome (AIDS) present diagnostic and therapeutic dilemmas to the intensive care physician. In this rare case, we describe a patient presenting with profound meningitis with cerebral sinus thrombosis secondary to Group A streptococcus mastoiditis. A 30 year-old HIV-infected man was brought to the ED because of acute-onset altered mental status. In the emergency department, the patient was stuporous, mumbling words, and combative. Temperature was 103.4 degrees, blood pressure 138/94, respiratory rate 18, and heart rate 145. Physical exam was positive for purulent discharge from left ear, with erythema on posterior wall of the left ear, and nuchal rigidity. The patient was admitted to the intensive care unit after being intubated for airway protection. He received intravenous dexamethasone, vancomycin, ceftriaxone, and acyclovir. A CT of the head without contrast demonstrated under-pneumatized left mastoid air cells, with no evidence of any mass effect. Lumbar puncture showed a cloudy CSF with an opening pressure of >60 cm/H20, with elevated protein, low glucose, high PMNs, and gram stain was negative. The CD4 count was 53. A brain MRI showed extensive left mastoiditis, left cerebellar cerebritis, multiple small acute infarcts in the supratentorial brain, and occlusion of the left transverse and sagital sinus, which was later confirmed by an MRA. He was started on anticoagulation with unfractioned heparin, later bridged to warfarin. The blood and ear drainage cultures grew penicillin-sensitive S. pyogenes, and antibiotics were appropriately managed. Inicidentally, Strongyloides larvae were noted on a stool exam after developing diarrhea, sand the patient was given 2 doses of ivermectin. On Day 6 with appropriate therapy, the patient’s mental status slowly improved and he was extubated. After the initial presentation, HAART was started and a total of six months anticoagulation with warfarin was recommended. The patient completed a total antibiotic course of 6 weeks, with a moderate neurologic recovery requiring aggressive physical therapy and a feeding tube for improved nutrition. Patients with AIDS present with complicated infectious courses. Although the intensivist is concerned with prototypic diseases such as toxoplasmosis, pneumocystis, and mycobacteria; common bacterial illness with sequelae such as group A streptococcus must be ascertained. Although cerebral sinus thrombosis and meningitis is more commonly seen in pediatrics as sequelae from mastoiditis, adult intensive care physicians must be aware of rare presentations in adults among immunocompromised patients.