Effective Highly Active Antiretroviral Therapy Research Articles

In silico drug repurposing approach to predict most effective HAART for HIV drug resistance variants prevalent in the Indian HIV-positive population.

HIV epidemics still exist as a major global public health burden, especially in middle- and low-income countries. Given the lack of approved vaccines, antiretroviral therapy (ART) remains the primary approach to reduce the mortality and morbidity linked to this disease. Effective treatment for HIV-1 requires the simultaneous administration of multiple drugs. However, the virus can show resistance to antiretroviral drugs, resulting in treatment failure. Therefore, this study focused on assessing the prevalence of mutations within the Indian HIV-positive population. After assessing the data, we intended to identify the most effective highly active ART (HAART) regimens for individuals with drug-resistant variants. Furthermore, our analysis revealed a spectrum of HIV mutations, with varying effects on protein stability. The significance of this analysis lies in its potential to optimize HAART selection for HIV-positive individuals by accounting for both prevalence and stability-altering mutations. By considering mutation effects on protein stability, we can modify treatment regimens, increasing the likelihood of therapy success and diminishing the risk of resistance. Moreover, this study contributes to the broader field of drug repurposing, offering insights into the rational design of antiretroviral therapies.

Effect of Highly Active Antiretroviral Therapy on Fundus Images and Retinal Microvessel Diameter in HIV/AIDS Patients

We aimed to investigate whether there were changes in fundus picture and retinal microvascularity of patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) who were treated with highly active antiretroviral therapy (HAART). From July 2015 to November 2016, 130 HIV/AIDS patients were collected by the Yunnan Institute of Traditional Chinese Medicine, including 63 treatment-naïve patients and 67 that received HAART for 12 months. Fundus picture lesions, retinal microvascular diameters, CD4+ T lymphocyte count and HIV-1 plasma viral loads were compared between the two groups. The recruited patients were mainly young and middle-aged, with more males than females. There were no significant differences in smoking history, comorbidities and opportunistic infections between the two groups. According to the analysis results from SPSS 20.0 software, the number of CD4+ T lymphocytes in the treated patients (563.34±2.56 cells/μL) increased significantly (P=0.009) as compared with untreated patients (451.37±2.10 cells/μL), and the HIV-1 plasma viral load reduced considerably (4794 vs 0 copy/mL, P=0.000). No significant differences were observed from the fundus picture of patients after effective HAART therapy, including the retinal artery diameter, venous diameter and arteriovenous diameter ratio.

Cytomegalovirus-Immune Recovery Retinitis After Initiation of Highly Active Antiretroviral Therapy: A Case Series.

PurposeTo delineate the characteristics and treatment of cytomegalovirus-immune recovery retinitis (CMV-IRR) in human immunodeficiency virus (HIV) patients with immune recovery under effective highly active antiretroviral therapy (HAART) regimen.MethodsWe reported four patients with HIV who were diagnosed with CMV-IRR soon after effective HAART. Plasma levels of CD4 T cells, HAART regimen, and other clinical and laboratory characteristics of the four patients were described. Patients were monitored for ocular manifestations and clinical signs under effective ocular and systemic anti-cytomegalovirus (CMV) and corticosteroid treatment for 12 months.ResultsWith HAART, plasma levels of CD4 T cell counts rose remarkably. The mean baseline CD4 count of the four patients was 14.5 (range from 7 to 33) cells/μl before HAART and 183.25 (range from 153 to 220) cells/μl when diagnosed with CMV-IRR. Ophthalmic examination demonstrated severe vitreous opacities and necrotizing retinitis, intraretinal hemorrhages, and vasculitis. A large number of CMV sequencing was detected by DNA sequencing of vitreous samples. All four patients were recovered from CMV-IRR with anti-CMV and corticosteroid treatment.ConclusionsCytomegalovirus-immune recovery retinitis is a new diagnosis of HIV-associated ocular complication under HAART. These findings suggest that the immunological effects of HAART may accelerate the CMV retinitis in patients with very low initial CD4 T cell counts. HIV patients are recommended to have a thorough fundus examination before HAART initiation and a close follow-up especially in those with low CD4 counts to avoid the progression of CMV retinitis.

Non-HIV Related Non-Communicable Diseases in HIV Patients

Authors examined the impact of additional factors on fatalities in Chronic HIV patient populations and should have remained on highly active antiretroviral therapy (HAART) for the at least 1 year: Inadequate response to HAART and the existence of AIDS-defining illnesses, depression, and drug and alcohol abuse, and especially in comparison the fatalities to that of the overall demographic. The enhanced rates of mortality in HIV-infected people are primarily impact on risk variables that can be recognized just before to or during the introductory phase of antiretroviral treatment. The fatality rate in patient populations without risk variables who are on effective HAART is virtually identical to something like the non-HIV-infected inhabitants. The significance of a holistic solution for lipid accumulation, cardiovascular, and glomerular comorbidity supervisors in the lengthy effective monitoring of chronic HIV old patients cannot be exaggerated.

Effects of Artesunate Tablet on Immune Activation and Reconstitution Among Highly Active Antiretroviral Therapy-Treated Patients with Incomplete Immune Responses

The level of T cell activation is a better predictor of CD4+ T cell depletion in highly active antiretroviral therapy (HAART) patients than viral load. Artesunate is an artemisinin derivative that has an immunomodulatory effect. This study investigated whether artesunate tablet reduces T cell activation and improves immune reconstitution among patients with suboptimal immune recovery despite receiving long-term effective HAART. This was a randomized prospective parallel open-label trial consisting of 45 participants whose plasma HIV load was effectively suppressed by HAART for >18 months and who had CD4+ T cell counts of <300 cells/μL or an increase of <20% from baseline. The patients were randomized 2:1 into the artesunate group or the control group and received artesunate tablets (orally, 50 mg two times daily) combined with HAART or HAART alone, respectively. T cell subsets, activation markers, clinical symptoms, viral load, and side effects were assessed. By 48 weeks, artesunate tablet did not improve CD4+ T cell recovery or reduce the activation of T cell subsets but induced in a smaller decline in the expression of T cell activation markers among HAART patients with incomplete immune responses. However, artesunate tablet did appear to reduce the level of T cell apoptosis. One subject developed moderate anemia. Long-term use of artesunate tablet is unlikely to produce substantial clinical benefits in patients receiving HAART who exhibit an incomplete immune response.

Anti-Retroviral Protease Inhibitors Regulate Human Papillomavirus 16 Infection of Primary Oral and Cervical Epithelium.

Simple SummaryIn 2016, globally, 36.7 million people were living with Human Immunodeficiency Virus (HIV), of which 53% had access to anti-retroviral therapy (ART) (UNAIDS 2017 Global HIV Statistics). The risk of Human Papillomavirus (HPV) associated oropharyngeal, cervical and anal cancers are higher among patients infected with HIV in the era of ART. Generally, HPV infections are self-limiting, however, persistent HPV infection is a major risk to carcinogenic progression. Long intervals between initial infection and cancer development imply cofactors are involved. Co-factors that increase infectivity, viral load, and persistence increase risk of cancer. We propose that the ART Protease Inhibitors (PI) class of drugs are novel co-factors that regulate HPV infection in HIV-infected patients. We developed a model system of organotypic epithelium to study impact of PI treatment on HPV16 infection. Our model could be used to study mechanisms of HPV infection in context of ART, and for developing drugs that minimize HPV infections.Epidemiology studies suggest that Human Immunodeficiency Virus (HIV)-infected patients on highly active anti-retroviral therapy (HAART) may be at increased risk of acquiring opportunistic Human Papillomavirus (HPV) infections and developing oral and cervical cancers. Effective HAART usage has improved survival but increased the risk for HPV-associated cancers. In this manuscript, we report that Protease Inhibitors (PI) treatment of three-dimensional tissues derived from primary human gingiva and cervical epithelial cells compromised cell-cell junctions within stratified epithelium and enhanced paracellular permeability of HPV16 to the basal layer for infection, culminating in de novo biosynthesis of progeny HPV16 as determined using 5-Bromo-2′-deoxyuridine (BrdU) labeling of newly synthesized genomes. We propose that HAART/PI represent a novel class of co-factors that modulate HPV infection of the target epithelium. Our in vitro tissue culture model is an important tool to study the mechanistic role of anti-retroviral drugs in promoting HPV infections in HAART-naïve primary epithelium. Changes in subsequent viral load could promote new infections, create HPV reservoirs that increase virus persistence, and increase the risk of oral and cervical cancer development in HIV-positive patients undergoing long-term HAART treatment.

Fundus manifestations and HIV viral loads of AIDS patients before and after HAART.

To investigate the fundus manifestations and human immunodeficiency virus (HIV) viral loads of acquired immune deficiency syndrome (AIDS) patients before and after highly active antiretroviral therapy (HAART). This retrospective study included 21 AIDS patients (42 eyes) who presented to the Department of Ophthalmology, Peking Union Medical College Hospital, from 2007 to 2011. Among the patients, 16 showed a good response to HAART, 3 presented drug resistance and 2 were pre-HAART. All patients underwent comprehensive ophthalmic examinations. The HIV viral loads and the CD4+ T-cell counts were also determined. The best-corrected visual acuity (BCVA) of 38 eyes (19 patients) was improved, and cytomegalovirus retinitis (CMVR) in 5 eyes (3 patients) regressed after HAART. Furthermore, 16 patients treated with effective HAART had decreased plasma HIV viral loads (<78 copies/mL) and increased CD4+ T-cell counts (343±161 cells/µL, P<0.005), but the HIV viral load in tears was still detected at 2404 copies/mL. The CD4+ T-cell count was lower in the CMVR group than in the non-CMVR group (P=0.022), but the HIV viral load in the tears was not significantly different between the two groups (P=0.439). Most patients with AIDS show a good viral response with a decreased HIV viral load and an increased CD4+ T-cell count in plasma after HAART. However, the HIV viral load remain quite high in the tear samples. Based on our results, we suggest that AIDS patients undergo long-term HAART that should not be interrupted.

Regulatory T-lymphocyte subsets in patients with HIV-infection receiving highly active antiretroviral therapy

Background. The reason why HIV-infected patients receiving highly active antiretroviral therapy (HAART) suffer from the increased immune activation remains elusive. Regulatory T-cells (Treg) are able to control immune activation, but their quantity may vary due to the infection. The aim of this work was to estimate the number and subsets of Tregs in HIV-positive patients receiving virologically effective HAART.Materials and methods. The CD4+ T-lymphocyte (CD3+CD4+) and Treg (CD3+CD4+FOXP3+) quantities were determined by flow cytometry. Treg subsets were assessed based on the FOXP3 expression level. The state of T-cell activation was established according to the simultaneous expression of CD38 and HLA-DR molecules.Results. It was shown that HIV-positive patients compared to healthy people have reduced CD4+ T-lymphocyte counts despite virologically effective HAART. At the same time in HIV-infected people, Treg absolute numbers were only slightly decreased. Moreover, the major part of Treg pool in their blood consisted of lymphocytes with a high level of FOXP3 expression that corresponded to the phenotype of cells with the highest suppressor activity. However, an increased relative amount of activated CD4+ T-lymphocytes was retained in the HIV-infected individuals’ blood.Conclusion. In HIV-infected patients who received HAART in time and whose treatment resulted in an effective HIV viral load suppression and a satisfactory CD4+ T-cell counts increase, a relatively large pool of peripheral Tregs is maintained. However, these lymphocytes are not enough to fully control immune activation that develops against the background of chronic lentivirus infection.

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

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

Mother-to-child HIV transmissions in Israel, 1985-2011.

Mother-to-child transmission (MTCT) is the leading cause of paediatric HIV-infection in Israel. This study aimed to assess MTCT rates and analyse temporal changes in relation to highly active antiretroviral therapy (HAART) introduction in 1996. This historical prospective study included all HIV-infected women who delivered in Israel between 1988 and 2011. Demographic, clinical, laboratory and therapy characteristics were compared between HIV-infected newborns with all others, and between infants born before and after 1996. Of all 796 infants born in Israel to HIV-infected women, 25 (3·1%) were infected. MTCT rates decreased significantly after HAART introduction compared with infants who were born before 1996 (16·3% vs. 1·7%). Mothers who infected vertically were more likely to be younger, Ethiopian-born, delivered trans-vaginally, not treated with HAART during pregnancy/labour and delivered before 1996 compared with mothers who did not transmit the HIV to their neonates. Newborns who did not receive antiretroviral therapy postpartum were more commonly HIV-infected and their mortality rate was higher. In conclusion, HAART during pregnancy/labour decreased MTCT significantly. Most MTCT in Israel was recorded among Ethiopian migrants, yet, in decreasing rates. Continuous efforts should be employed to encourage early HIV testing and allow effective HAART to pregnant women who belong to a key risk-group.

TB-HIV co-infection: a catastrophic comradeship.

The symbiotic association of tuberculosis (TB) and HIV poses a challenge to human survival. HIV complicates every aspect of TB including presentation, diagnosis and treatment. HIV-TB patients encounter unique problems like drug-drug interactions, cumulative toxicity, immune reconstitution inflammatory syndrome (IRIS), lower plasma drug levels and emergence of drug resistance during treatment despite adherence. TB may also be overdiagnosed in HIV due to a number of diseases that closely resemble TB. Notable among them are non-tuberculous mycobacteria, Pneumocystis Jirovecii and Nocardia. Even though diagnostic procedures have improved over the years, patients in developing countries usually seek health care at later stage of the disease. Research data ascertains the duration of therapy for TB to be 6months with rifampicin and isoniazid, reinforced with ethambutol and pyrazinamide in the first 2months. The schedule of therapy is still debatable with daily regimens being preferred in the context of HIV. Many reasons exist for persistence of Mycobacterium Tuberculosis (M.TB) in sputum, or delayed-clearance of TB from sputum smears in HIV, apart from emergence of drug resistance and non-compliance. Acquired rifampicin resistance (ARR) is a unique phenomenon complicating HIV-associated TB when an intermittent regimen of antituberculosis therapy (ATT) is used without timely initiation of highly active antiretroviral therapy (HAART), especially in patients harbouring isoniazid-resistant strains Immune restoration is often incomplete ('swiss cheese' pattern) even with effective HAART if not started early. Immune reconstitution inflammatory syndrome (IRIS) is the paradoxical worsening of the patient's condition often with radiological deterioration, due to an enhanced immune response with HAART. IRIS occurs despite an effective virological suppression and a favourable response to ATT. The incidence of IRIS in HIV has reached up to 54%, requiring utilization of experts and tertiary care which forms an obstacle to the decentralization of patients in the ART programme. Research in HIV-TB immunology and management needs further exploration in order to understand thediseases and offer appropriate treatment. The following paragraphs provide scientific evidences generated through research that could potentially guide management.

Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART.

BackgroundImmunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE).MethodsPatients highly-active antiretroviral therapy (HAART) with <200 CD4+/μl and achieving HIV-RNA <50 copies/ml within 12 (±3) months were categorized as INR if CD4+ T-cell count at year 1 was <200/μl. Predictors of nADE (malignancies, severe infections, renal failure—ie, estimated glomerular filtration rate <30 ml/min, cardiovascular events and liver decompensation) were assessed using multivariable Cox models. Follow-up was right-censored in case of HAART discontinuation or confirmed HIV-RNA>50.Results1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+ were 77/μl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9% infectious, 17.4% renal, 17.4% cardiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95%CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE.ConclusionsPatients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.

Drug susceptibility to etravirine and darunavir among Human Immunodeficiency Virus Type 1-derived pseudoviruses in treatment-experienced patients with HIV/AIDS in South Korea.

BackgroundIn South Korea, about 20 types of antiretroviral drugs are used in the treatment of patients with human immunodeficiency virus/acquired immune deficiency syndrome. Since 2010, raltegravir, etravirine, and darunavir have been spotlighted as new drugs for highly active antiretroviral therapy (HAART)-experienced adults with resistant HIV-1 in South Korea. In this study, we investigated potential susceptibility of pseudoviruses derived from treatment-experienced Korean patients to etravirine vs efavirenz and to darunavir vs amprenavir and indinavir using a modified single-round assay.MethodsPseudoviruses derived from nine treatment-experienced patients infected with HIV-1 were investigated by comparison with the wild-type strain pNL4-3. The 50% inhibitory concentration (IC50) values were calculated and drug susceptibility was compared. The intensity of genotypic drug resistance was classified based on the ‘SIR’ interpretation of the Stanford data base.ResultsDrug susceptibility was generally higher for etravirine and darunavir compared with efavirenz, amprenavir, and indinavir in pseudoviruses derived from treatment-experienced patients. Pseudoviruses derived from patients KRB4025 and KRB8014, who exhibited long-term use of protease inhibitors, showed an outside of tested drug concentration, especially for amprenavir and indinavir. However, they exhibited a lower fold-change in resistance to darunavir.ConclusionsEtravirine and darunavir have been used in HAART since 2010 in South Korea. Therefore, these antiretroviral drugs together with other newly introduced antiretroviral drugs are interesting for the optimal treatment of patients with treatment failure. This study may help to find a more effective HAART in the case of HIV-1 infected patients that have difficulty being treated.

HIV/AIDS and bone: an unrecognised threat?

Since the first isolated cases of acquired immunodeficiency syndrome (AIDS) was described in homosexual men in the United States in 1981, the Human Immunodeficiency Virus (HIV) infection has spread globally affecting 33 million people. With the advent of highly active antiretroviral therapy (HAART) there has been a paradigm shift in the clinical profile of patients with HIV. Prior to effective HAART, patients usually had a progressive fatal course characterised by recurrent opportunistic infections. Since the introduction of HAART, which has dramatically improved these patients survival, conditions associated with accelerated aging, have come to the fore, especially cardiovascular disease, malignancy, diabetes mellitus and metabolic bone disease. The aim of this review is to increase the knowledge of HIV associated metabolic bone disease, alert health care providers of the possible bone complications associated with HIV and HAART and stimulate further research in the field.

Serum protein electrophoresis under effective control of HIV-1 disease progression.

In this report, we compared the serum protein electrophoresis (SPE) patterns in a subset of HIV-1-infected subjects who did not progress to AIDS without antiretroviral treatment with those in whose control of disease progression was achieved by highly active antiretroviral therapy (HAART). SPE and immunofixation electrophoresis were performed on Helena Electrophoresis System according to manufacturer's instructions. The percentage of SPE abnormalities, resembling chronic inflammation, was significantly higher in HIV-1-infected subject without HAART compared with those under HAART (p = 0.001). The majority of individuals under HAART showed evidence of oligoclonal bands on the γ-band against a polyclonal background compared with those without HAART but ß-γ-band bridging was more evident. Immunofixation pattern was consistent with oligoclonal hypergammaglobulinaemia of IgG kappa type, which was found to be more intense in group without HAART. HIV clinical status did not show appreciable effect on the SPE pattern in subjects without HAART. However, under effective HAART, subjects with better CD4 T-cell count were associated with higher γ-globulin band. In group without HAART, acute infection was found to be associated the higher γ-globulin fraction compared with chronic infection. The opposite was the case under effective HAART. HIV infected subjects that did not progress to AIDS were associated with markedly abnormal SPE pattern. Overall results reflect the host ability compensate defective cellular immunity in HIV-1 infection with humoral immune responses. These findings underscore the usefulness of SPE monitoring HIV disease management and identifying individuals that may not progress to full-blown AIDS in the absence of treatment.

HIV-associated progressive multifocal leukoencephalopathy: longitudinal study of JC virus non-coding control region rearrangements and host immunity

John Cunningham virus (JCV), the etiological agent of progressive multifocal leukoencephalopathy (PML), contains a hyper-variable non-coding control region usually detected in urine of healthy individuals as archetype form and in the brain and cerebrospinal fluid (CSF) of PML patients as rearranged form. We report a case of HIV-related PML with clinical, immunological and virological data longitudinally collected. On admission (t0), after 8-week treatment with a rescue highly active antiretroviral therapy (HAART), the patient showed a CSF-JCV load of 16,732 gEq/ml, undetectable HIV-RNA and an increase of CD4+ cell count. Brain magnetic resonance imaging (MRI) showed PML-compatible lesions without contrast enhancement. We considered PML-immune reconstitution inflammatory syndrome as plausible because of the sudden onset of neurological symptoms after the effective HAART. An experimental JCV treatment with mefloquine and mirtazapine was added to steroid boli. Two weeks later (t1), motor function worsened and MRI showed expanded lesions with cytotoxic oedema. CSF JCV-DNA increased (26,263 gEq/ml) and JCV viremia was detected. After 4 weeks (t2), JCV was detected only in CSF (37,719 gEq/ml), and 8 weeks after admission (t3), JC viral load decreased in CSF and JCV viremia reappeared. The patient showed high level of immune activation both in peripheral blood and CSF. He died 4 weeks later. Considering disease progression, combined therapy failure and immune hyper-activation, we finally classified the case as classical PML. The archetype variant found in CSF at t0/t3 and a rearranged sequence detected at t1/t2 suggest that PML can develop from an archetype virus and that the appearance of rearranged genotypes contribute to faster disease progression.

Analysis of death causes of 345 cases with HIV/AIDS in Guangdong area

To analyze the death causes of 345 cases with HIV/AIDS in Guangdong area. The situations of 345 hospitalized death cases with HIV/AIDS were conducted by retrospective analysis. (1)There were total 3406 hospitalized cases with HIV/AIDS in a hospital from January 2001 to December 2011 and 345 cases died, the fatality rate was 10. 13%. Since 2005 the introduction of free anti-viral treatment, the fatality rate of HIV/AIDS declined. The fatality rate of the patients whose CD4+ T lymphocyte counts <200 cells/microl was 14.61% (299/2046) and it was significantly higher than that of patients whose CD4 T lymphocyte counts >or=200 cells/microl (P <0.01). (2) 99.42% of the death cases had more than one kind of opportunistic infections (OI) and there were 924 cases of OI totally. 84. 64% of OI related to the death directly. Fungal infection was the most common in OI, followed by bacterial infection. Most OI occurred in the lungs, mouth, other systemic disseminated diseases, gastrointestine, central nerver system, septicemia, skin. The AIDS defining opportunistic infections such as several pneumonia, disseminated penicilliosis marneffei and CNS infections accounted for 29.65%. Other factors that caused HIV/AIDS death included opportunistic tumors, HIV related disease and non AIDS-related disease accounted for 15.36%. No accepted effective highly active antiretroviral therapy (HARRT) also constituted factors of death. Among cases which accepted HARRT treatment, only 6.96% had the period of treatment over three months. The fatality rate of end-stage AIDS patients was high and the opportunistic infections was the most important cause of death. Early diagnosis and treatment for opportunistic infections, timely effective HARRT were the key to improve the quality of life of AIDS patients.

Graves’ Disease as a Late Manifestation of Immune Reconstitution Syndrome after Highly Active Antiretroviral Therapy in an HIV-1 Infected Patient

Context: Highly active antiretroviral therapy (HAART) inhibits the HIV replication and consequently increases CD4 levels and decreases viral load. This immune system improvement can trigger various immunological phenomena, entity called Immune Reconstitution Syndrome (IRS). Graves’ disease is a late Immune Reconstitution consequence. Patient: We report the case of a 48 years old man with HIV infection who developed Graves’ disease three years after he was on effective HAART because of the Immune Reconstitution Syndrome. At presentation he had a very low CD4 T-cell count (17 cells/μL). When he started HAART he presented a lipodystrophy syndrome. HAART was changed because of the persistent low CD4-T cells count (less than 100 cell/μL). Afterwards serum lipid levels began to decrease and that was the first manifestation of Graves’ disease, which was diagnosed when CD4 T-cells increased up to 343 cell/μL. Our patient developed Graves’ disease 36 months after initiating effective HAART with protease inhibitors which was coincident with viral suppression and a rise of CD4 T cells. Conclusion: The most immunosuppressed patients with a CD4 T cell count less than 100 cells/μL are at greatest risk for the development of Immune Reconstitution Syndrome after HAART initiation. We conclude that clinicians will have to consider the importance of the early diagnosis of thyroid disease to bring an adequate treatment.

Immune recovery uveitis masked as an endogenous endophthalmitis in a patient with active CMV retinitis.

Cytomegalovirus (CMV) retinitis may occur in profoundly immunocompromised patients and be the initial AIDS-defining infection. The incidence and prevalence of CMV retinitis has declined substantially in the era of highly active antiretroviral therapy (HAART); nevertheless, it remains a leading cause of ocular morbility. We report the case of a 40-year-old man with blurred vision and pain in the right eye, three weeks after the initiation of effective HAART treatment. Ocular examination revealed a panuveitis causing an anterior chamber reaction with hypopyon and a dense vitreous haze. An endogenous endophthalmitis was suspected and treatment was ensued, without improvement. A vitreous tap was performed, and a positive polymerase chain reaction for CMV was found. A diagnosis of immune recovery uveitis (IRU) was made, and the patient responded to treatment with valganciclovir and dexamethasone. IRU is an intraocular inflammation that develops in patients with HAART-induced immune recovery and inactive CMV retinitis, although cases of active CMV retinitis have been described. Presentation with panuveitis and hypopion is rare and may be misleading regarding diagnosis and management.

A Novel Immunogen to Modulate Cytokine Production and Promote Immune System Reconstitution in HIV–AIDS

This 'proof of concept' study was implemented in anticipation of identifying and testing a novel antigen of human origin as a potential immunogen in a paradigm that emphasizes immunomodulation and immune system reconstitution as requisites to the development of an effective human immunodeficiency virus (HIV)-acquired immune deficiency syndrome vaccine. Fifteen HIV-infected, highly active antiretroviral therapy (HAART) naive, otherwise healthy male seropositive patients were stratified by [CD4+] into 3 groups of 5 patients: group 1 >500/mm; group 2 > 250/mm but <500/mm; and group 3 < 250/mm. Five healthy male subjects were used as controls. Replicate peripheral blood mononuclear cell (PBMC) [H]thymidine uptake phytohemaglutinin-stimulated proliferation studies, and serum cytokine assays were carried out in the presence or absence of Kveim antigen at dilutions ranging from 0.001 to 100 μg/mL. Serum cytokines [interleukin-2 (IL-2), IL-4, IL-6, interferon gamma, and tumor necrosis factor alpha] were assayed using standardized methodology. Nonparametric statistical analyses and linear regression analysis were used to test for statistical significance and strength of associations. PBMCs harvested from HIV-infected patients and incubated, ex vivo, demonstrated reproducible, antigen concentration-dependent changes in cytokine production over a range of antigen concentrations (0.001-100 μg/mL) in contrast to antigen-naive PBMCs and controls. Significant correlations were demonstrated between antigen concentration and the amount of cytokines secreted. The magnitude of the cytokine response and the patterns of cytokine secretion were HIV group-specific and could be used to identify and distinguish between the 3 groups of HIV-infected subjects. A shift toward the production of type 1-like (Th1) cytokines characteristically seen in systemic sarcoidosis and associated with effective HAART was seen when patterns of cytokine secretion were compared between antigen exposed and antigen-naive PBMCs. PBMCs harvested from seropositive HIV-infected patients and exposed to the Kveim antigen have the following properties: (1) They demonstrate proliferation and exhibit an antigen concentration-dependent secretion of cytokines. The magnitude of the cytokine response can be used to identify and distinguish between groups of seropositive patients stratified by [CD4+]. (2) These PBMCs secrete cytokines in patterns suggestive of a shift to a type 1-like (Th1) response characteristic of HAART and sarcoidosis as opposed to the type 2-like (Th2) cytokine profile characteristic of HIV-acquired immune deficiency syndrome.