Opportunistic Infections In AIDS Research Articles

Indigenous traditional knowledge of medicinal plants used for the management of HIV / AIDS opportunistic infections in Katsina State, Nigeria

Background: Medicinal plants are widely used for the management of many diseases including HIV / AIDS opportunistic infections in Katsina State, North-western part of Nigeria. The usage of those plants is, however, poorly documented. Method: An ethnobotanical study was conducted to document medicinal plants used for the management of HIV / AIDS opportunistic infections in three Local Government Areas (one from each Senatorial Zone) of Katsina State, Nigeria. Information was obtained through a semi-structured questionnaire administered to 150 respondents comprising traditional healers, herbalists, farmers and HIV / AIDS patients. Results: The survey revealed 48 plant species distributed among 44 genera and 28 families. The highest Relative Frequency of Citation was observed in Anogeissus leiocarpa (DC.) Guill. and Perr (0.75). Fabaceae represented by 11 species appeared to be the most utilised family. Highest Informant Consensus factor was observed in abnormal vaginal discharge and genital ulcer. Most of the cited species are trees that are sourced from the wild and majority of medications are prepared in the form of decoction which is taken orally. The most used plant parts were leaves (40%). Conclusion: The study revealed substantial numbers and knowledge of medicinal plants used for the treatment of HIV / AIDS related infections in Katsina State, Nigeria. Further investigations to establish the pharmacological potentials of the cited species with regard to the treatment of HIV / AIDS are highly recommended. Keywords: Ethnobotanical survey; HIV / AIDS; Opportunistic infections; Medicinal plants; Katsina state

Distribution Characteristics of Drug Susceptibility Test Results of Tuberculosis and Non-Tuberculous Bacilli in Patients with Opportunistic Infections of AIDS

Objective: To understand the distribution of drug susceptibility test results of opportunistic infections of tuberculosis and non-tuberculous bacilli in AIDS patients. Methods: The AIDS patients who were hospitalized in our hospital from January 2016 to June 2019 were collected as the research objects, and patients with opportunistic tuberculosis and non-tuberculous bacilli from AIDS patients were screened for drug susceptibility tests, and the distribution characteristics of drug susceptibility were analyzed. Results: 179 strains of tuberculosis and non-tuberculous mycobacteria were isolated from the specimens of AIDS patients, including 135 cases of tuberculosis mycobacteria and 44 cases of non-tuberculous mycobacteria. In the results of the drug susceptibility test, most strains of Mycobacterium tuberculosis showed sensitivity to commonly used drugs, and a few strains showed resistance; most strains of non-tuberculous mycobacteria showed resistance, and a few strains showed sensitivity. Conclusion: AIDS opportunistic infection of Mycobacterium tuberculosis and non-tuberculous mycobacteria have significant differences in drug sensitivity test results. Timely detection and analysis are of great significance to the diagnosis and treatment of the disease.

The HIV Outpatient Study-25 Years of HIV Patient Care and Epidemiologic Research.

The clinical epidemiology of treated HIV infection in the United States has dramatically changed in the past 25 years. Few sources of longitudinal data exist for people with HIV (PWH) spanning that period. Cohort data enable investigating new exposure and disease associations and monitoring progress along the HIV care continuum. We synthesized key published findings and conducted primary data analyses in the HIV Outpatient Study (HOPS), an open cohort of PWH seen at public and private HIV clinics since 1993. We assessed temporal trends in health outcomes (1993-2017) and mortality (1994-2017) for 10 566 HOPS participants. The HOPS contributed to characterizing new conditions (eg, lipodystrophy), demonstrated reduced mortality with earlier HIV treatment, uncovered associations between select antiretroviral agents and cardiovascular disease, and documented remarkable shifts in morbidity from AIDS opportunistic infections to chronic noncommunicable diseases. The median CD4 cell count of participants increased from 244 cells/mm3 to 640 cells/mm3 from 1993 to 2017. Mortality fell from 121 to 16 per 1000 person-years from 1994 to 2017 (P < .001). In 2010, 83.7% of HOPS participants had a most recent HIV viral load <200 copies/mL, compared with 92.2% in 2017. Since 1993, the HOPS has been detecting emerging issues and challenges in HIV disease management. HOPS data can also be used for monitoring trends in infectious and chronic diseases, immunologic and viral suppression status, retention in care, and survival, thereby informing progress toward the Ending the HIV Epidemic initiative.

Pantothenic Acid Biosynthesis in the Parasite Toxoplasma gondii: a Target for Chemotherapy

Toxoplasma gondii is a major food pathogen and neglected parasitic infection that causes eye disease, birth defects, and fetal abortion and plays a role as an opportunistic infection in AIDS. In this study, we investigated pantothenic acid (vitamin B5) biosynthesis in T. gondii. Genes encoding the full repertoire of enzymes for pantothenate synthesis and subsequent metabolism to coenzyme A were identified and are expressed in T. gondii. A panel of inhibitors developed to target Mycobacterium tuberculosis pantothenate synthetase were tested and found to exhibit a range of values for inhibition of T. gondii growth. Two inhibitors exhibited lower effective concentrations than the currently used toxoplasmosis drug pyrimethamine. The inhibition was specific for the pantothenate pathway, as the effect of the pantothenate synthetase inhibitors was abrogated by supplementation with pantothenate. Hence, T. gondii encodes and expresses the enzymes for pantothenate synthesis, and this pathway is essential for parasite growth. These promising findings increase our understanding of growth and metabolism in this important parasite and highlight pantothenate synthetase as a new drug target.

Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy

Polyomavirus JC (JCV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a demyelinating infection of oligodendrocytes in the brain. PML, a frequently fatal opportunistic infection in AIDS, has also emerged as a consequence of treatment with several new immunosuppressive therapeutic agents. Although nearly 80% of adults are seropositive, JCV attains an ability to infect glial cells in only a minority of people. Data suggest that JCV undergoes sequence alterations that accompany this ability, and these changes can be derived from an archetype strain by mutation, deletion, and duplication. While the introductory source and primary tissue reservoir of JCV remain unknown, lymphoid cells have been identified as potential intermediaries in progression of JCV to the brain. This review is focused on sequence changes in the noncoding control region (NCCR) of the virus. We propose an adaptive mechanism that involves a sequential series of DNA replication-driven NCCR recombination events involving stalled DNA replication forks at NCCR palindromic secondary structures. We shall describe how the NCCR sequence changes point to a model in which viral DNA replication drives NCCR recombination, allowing JCV adaptation to different cell types in its progression to neurovirulence.

Decreasing incidence of cryptococcal meningitis in West Africa in the era of highly active antiretroviral therapy

Cryptococcosis remains a major opportunistic infection in AIDS in sub-Saharan Africa, but few data exist from its western part. We report data from Bobo Dioulasso University Hospital, Bobo-Dioulasso, Burkina Faso, with a steady decline from 14 to two cases per year from 2002 to 2010 which contrasts with the increase (from 147 to 3940) of patients on antiretroviral therapy (ART). Better ART availability decreases the incidence of cryptococcosis in Burkina Faso.

Clinical and immunological presentation of new HIV-infected patients in an outpatient clinic

Results 311 new patients were observed (305 HIV-1 infected and 6 HIV-2 infected), with a mean age of 42 ± 13,7 years. 218 (70%) patients were men. Risk factor for HIV-infection was sexual in 271 (87%) patients (18% were homo-bisexual). At the time of diagnosis the mean CD4+ cell count was 333 ± 305 cells/mm3; 132 (42,4%) patients had CD4 cell count <200/mm. In 89 (28,6%) patients an AIDS-defining illness was diagnosed simultaneously with HIV-infection diagnosis; 43% of these were tuberculosis. After a mean follow-up of 15 ± 9,7 months 27 (8,6%) patients died, 24/27 (88,8%) with AIDS and the other 3 patients one each with eosophageal cancer, hepatic failure and MSSA sepsis,. In 22/27 (81,4%) of the deceased patients the CD4 cell count was <200 cells/mm at the time of the HIV diagnosis. Discussion In the last 3 years, 42% of the new diagnosed patients had a serious immunological deficit. In 28% of them HIV-infection was diagnosed simultaneously with a defining AIDS opportunistic infection. The fact that 81,4% of the deceased patients had a CD4 cell count <200/mm at diagnosis shows that HIV-infection diagnosis was done too late for ART to be of benefit.

Acquired immunodeficiency syndrome and opportunistic infections

This article presents a clinical case of late diagnosis of cerebral toxoplasmosis and cytomegalovirus retinitis of right eye in a 32-year-old patient who was unaware of her HIV status. In addition, this article reviews the literature reflecting clinical, diagnostic, and treatment issues of some opportunistic infections in AIDS.

Kryptokokkenmeningoenzephalitis bei einem HIV-positiven Patienten mit Rezidiv bei Resistenz gegenüber Fluconazol und IRIS

□ History and Clinical Findings: A 24-year-old HIV-positive patient was admitted to hospital on account of increasing headache. □ Investigations: On admission, a patient with severe headache, nausea and vomiting but without neurologic deficiencies was seen. The diagnosis of a cryptococcal meningoencephalitis could be confirmed by direct detection of cryptococci in the liquor. □ Treatment and Course: The patient was treated with a combination of fluconazole, flucytosine and amphotericin B, and an antiretroviral therapy (ART) was started on account of the severe immunodeficiency. The patient improved during the following weeks, and fluconazole was administered as maintainance therapy. About 2 months later, the patient presented again with severe headache. On lumbar puncture, a great amount of cryptococci could be detected, and the antimycotic combination therapy was restarted. An antimycotic testing of the cryptococci revealed a partial resistance to fluconazole. Therefore, fluconazole was replaced by voriconazole which has been continued ever since. Cryptococci could not be detected on further investigations of the liquor. The patient's condition worsened again 8 months after initiation of the ART. MR scan showed a slight cerebral edema. There was no hint of an opportunistic infection nor of a lymphoma. The complaints were supposed to be due to an immune restoration inflammatory syndrome (IRIS), and administration of high steroid dosages was started. The complaints resolved within 48 h, and the patient's condition has been stable ever since (19 months). □ Conclusion: Cryptococcal meningoencephalitis is an opportunistic infection in AIDS. Therapeutically, various regimens containing two to three different antimycotic drugs show good efficacy but resistance to antimycotics has to be considered. As in other HIV associated infections, an IRIS has to be taken into account.

I-23 Opportunistic infections in AIDS: Thai experience

I-23 Opportunistic infections in AIDS: Thai experience

Rates of hospitalizations and associated diagnoses in a large multisite cohort of HIV patients in the United States, 1994–2005

To assess temporal trends in the rates of hospitalizations and associated diagnoses among HIV-infected patients before and during the era of highly active antiretroviral therapy. A prospective cohort study of 7155 patients enrolled in the HIV Outpatient Study at 10 US HIV clinics. We evaluated rates of hospitalizations for major categories of medical conditions during 1994-2005 and modeled trends in these rates using multivariable Poisson regression models for repeated observations. We assessed patient characteristics associated with hospitalization using multiple logistic regression. The rates of hospitalizations (per 100 person-years) fell from 24.6 in 1994 to 11.8 in 2005 (P < 0.0001). The rates of hospitalizations for AIDS opportunistic infections decreased from 7.6 in 1994-1996 to 1.0 in 2003-2005 (P < 0.0001). AIDS opportunistic infections were present at 31% of hospitalizations in 1994-1996 versus 9.5% in 2003-2005, and chronic end-organ disease conditions were present at 7.2% of such hospitalizations in 1994-1996 versus 14.3% in 2003-2005. Mean CD4+ cell count at hospitalization increased from 115 cells/mul in 1994 to 310 cells/mul in 2005. Factors independently associated with hospitalization in the highly active antiretroviral therapy era (1997-2005) included older age, history of substance abuse, lower CD4+ cell count, history of AIDS, and public health insurance. The rates of hospitalizations for HIV-infected patients declined substantially during 1994-2005, due mainly to reductions in the AIDS opportunistic infections. Compared with the period 1994-1997, patients in the highly active antiretroviral therapy era were hospitalized with higher CD4+ cell counts and more frequently for chronic end-organ conditions.

The New Challenges in management of HIV-infected patients

Dramatic advances in prevention and treatment of pediatric HIV infection occur in high-resource countries, but only 1% of the 2.3 million HIV-infected children live in these regions. Thus, two pediatric HIV epidemics have evolved, one in high-resource countries and one in low-resource countries. About the first epidemic, effective antiretroviral therapies for HIV in children have prolonged life and quality of life. As in adults, there has been evolution in causes of death over time, with decrease in AIDS-opportunistic infections and increase in ‘end-stage AIDS’ multiorgan failure, sepsis, and renal disease. In addition, spectrum of disease has changed: drug resistance (primary and acquired), lack of salvage drugs for children, complications of therapy, adherence, mental health, and adolescence-transition to adult care are the main problems that have emerged in the last years. In low-resource countries, few women know they are infected and there is poor access to antiretrovirals to prevent mother-to-child transmission, so children often present to health system with advanced disease and about 1000 infants are newly infected each day. Moreover, both diagnosis of infection in infants and drug access remain problematic: despite rapid progression and high mortality due to HIV in children, few receive treatment and, when available, it is started late. In this current evolving clinical context, we reviewed the epidemiology, clinical features, and treatment-related infectious complications of these two HIV-related epidemics.

Semisynthetic studies on the manzamine alkaloids.

Chemical transformation studies were conducted on (-)-8-hydroxymanzamine A ( 1), (-)-manzamine F ( 2), manzamine A ( 3), and (+)-8-hydroxymanzamine A ( 4), isolated from Indo-Pacific Acanthostrongylophora sponges. Thirteen new semisynthetic manzamine derivatives, including four Delta (34,35) manzamines ( 5, 6, 8, and 9) and the unprecedented manzamine derivative 17, are reported. The potent in vitro activities of the obtained semisynthetic manzamines against activated brain microglia and the AIDS opportunistic infection pathogen Mycobacterium tuberculosis are presented.

Genomic scale analysis of lateral gene transfer in Apicomplexan parasites: insights into early eukaryotic evolution, host-pathogen interaction and drug target development

The protozoan phylum Apicomplexa is comprised of >5000 species, including Toxoplasma gondii (a prominent opportunistic infection in AIDS), and the Plasmodium parasites responsible for malaria. Complete genome sequences are now available for several apicomplexan species, including both T. gondii and Plasmodium falciparum, making it possible to exploit comparative phylogenomic tools for insight into adaptations associated with intracellular parasitism, and in order to identify targets for therapeutic development. These parasites harbor a novel organelle, the 'apicoplast', which was acquired by endosymbiotic capture of a eukaryotic alga, and thus provides a dramatic example of lateral gene transfer (LGT). In order to determine the overall impact of LGT, we have employed phylogeny reconstruction to detect transfers on a genomicscale. Trees have been constructed for all genes in the Toxoplasma and Plasmodium genomes, and compared with a whole genome species treederived from 55 taxa represented in the orthologous protein database OrthoMCL-DB [1]. Non-apicomplexan specific ortholog groups containing4 to 100 sequences were examined, pruning outlying species based on their degree of connectivity to the group as a whole, and robustness of the resulting tree. A pilot study based on intensive manual curation of T. gondii genes coding for metabolic enzymes estimates that ~15% of these genes were acquired by LGT. Turning to the entire parasite genome(s), Horizstory software identifies 1552 groups where T. gondii gene placement contrasts with the species tree, and 1520 instances of potential LGTinvolving P. falciparum. In order to identify the most probable LGT events, we developed a strategy that ranks the probability ofLGT based on the taxonomic consistency of results for sibling species within the tree, and bootstrap support for the relevant internalnode(s). This 'LGTsmart' strategy yields a ranked list of probable lateral gene transfer events (Figure ​(Figure1)1) including 226 high confidence events that occurred at different times during the course of apicomplexan evolution. Many of these transfers involve genes exhibiting phylogenetic affinity with plants, consistent with the algal origin of the apicoplast endosymbiont. Additional, more recent, transfers appear to have a bacterial origin, and both classes of genes include promising targets for drug development. Interestingly, we also detected LGT of metazoan-like genes, possibly acquired through interaction with the host during adaptation to the parasitic lifestyle. Figure 1 Probable source of transfer events identified by the LGT smart algorithm. Parentheses indicate possible LGT events for each source clade; bold indicates high confidence transfers.

Bacterial Disease in HIV-Infected Patients

Bacterial Disease in HIV-Infected Patients

Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion

Although HAART has led to a reduction in overall mortality among HIV-infected individuals, its impact on death from specific causes is unknown. Twenty-two cohorts of HIV-infected individuals with known dates of seroconversion are pooled in the CASCADE collaboration. Causes of death (COD) were categorized into three AIDS-related and seven non-AIDS-related causes. The unknown causes were assigned a separate category. The cumulative incidence for each COD was calculated in the presence of the other competing COD, for the pre-HAART and HAART eras. A multivariate regression analyses for the cumulative rate of progression to the different COD was performed. A total of 1938 of 7680 HIV-seroconverters died. Pre-HAART, AIDS opportunistic infections (OI) was the most common COD, followed by unknown and HIV/AIDS-unspecified. In the HAART era, the cumulative incidence for all AIDS-related COD decreased, OI remaining the most important. Large reductions in death due to other infections and organ failure were seen. Cumulative death risk decreased in the HAART era for most causes. The effect of HAART was not the same for all risk groups. The cumulative risk of death from AIDS-related malignancies, OI and non-AIDS-related malignancies decreased significantly among homosexual men (MSM), whereas the risk of dying from (un)-intentional death increased significantly among injecting drug users (IDU). A non-significant increase in hepatitis/liver-related death was seen in MSM, IDU and haemophiliacs. Overall and cause specific mortality decreased following the introduction of HAART. OI remain the most common COD in the HAART era, suggesting that AIDS-related events will continue to be important in the future. Future trends in COD should be monitored using standardized guidelines.

Cancers et infection par le VIH : quelles associations ?

Purpose. – Morbidity and mortality related to neoplasia are increasing in HIV-infected patients. Current knowledge and key-points. – The incidence of AIDS opportunistic infections dramatically decreased since the introduction of highly active antiretroviral therapy (HAART). Among AIDS-cancers, the incidences of Kaposi sarcoma and of cerebral lymphoma decreased in a same way than AIDS infections but the incidences of systemic non-Hodgkin lymphoma and of cervical cancer decreased less than the others and remain higher than in the general population. This suggests that other factors than the quantitative immune reconstitution could be implicated. The most recent and large studies have also shown a 1.7 to 3 fold increased risk of developing non-AIDS cancers in HIV-infected patients when compared to the general population without significant impact of HAART on incidence curves. These malignancies include Hodgkin disease, lung, anal, head and neck cancers, hemopathies, and conjunctival cancers. Perspectives. – Epidemiologic survey will help to define priorities in terms of prevention and screening in this specific population and to evaluate interventions which should be systematically proposed (alcohol and tobacco cessation programs, viral coinfection). The own roles of HIV itself and of antiretrovirals as prooncogenic factors need to be assessed.

HIV, hepatitis C and HIV/hepatitis C virus co-infection in vulnerable populations

To describe basic patient demographic and clinical characteristics of HIV-infected and HIV/hepatitis C virus (HCV)-co-infected patients receiving care in the Department of Veterans Affairs (VA) with a focus on some patient factors that place such patients at an increased risk of poor health outcomes. An observational retrospective cohort study. The study cohort consisted of veterans in the VA Immunology Case Registry who received care in the VA in 2002. Of 18,349 HIV-infected patients, 6782 (37.0%) were HCV seropositive. Compared with HIV-alone-infected patients, HIV/HCV-co-infected patients were older, more likely to be men, more likely to be black or Hispanic, and more likely to report intravenous drug use as a risk factor for HIV acquisition. HIV/HCV-co-infected patients were more likely to have diagnoses of mental health illness, depression, alcohol abuse, substance abuse and hard drug abuse compared with HIV-alone-infected patients. Co-infected patients were less likely to have a history of an AIDS opportunistic infection ever and were less likely to have received HIV antiretroviral drugs in 2002. The VA's HIV and HIV/HCV-co-infected patient populations have very high rates of additional comorbid conditions that complicate both the pharmacological therapy and clinical course of both HIV and HCV infections. Given the overlap in viral illness and comorbidities, optimal models of integrated care need to be developed for populations with HIV, HCV, and HIV/HCV co-infection and who need substance abuse treatment or mental healthcare.

Newer Aminopyrimidinimino Isatin Analogues as Non‐Nucleoside HIV‐1 Reverse Transcriptase Inhibitors for HIV and Other Opportunistic Infections of AIDS: Design, Synthesis and Biological Evaluation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Newer aminopyrimidinimino isatin analogues as non-nucleoside HIV-1 reverse transcriptase inhibitors for HIV and other opportunistic infections of AIDS: design, synthesis and biological evaluation

Human immuno deficiency virus (HIV) weakens the immune system so that many opportunistic infections (OIs) like tuberculosis, hepatitis, bacterial infections etc can develop. In this paper, we designed aminopyrimidinimino isatin lead compound as a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with broad-spectrum chemotherapeutic properties for the effective treatment of AIDS and AIDS-related OIs. Compound 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[[N 4-[3'-(4'-amino-5'-trimethoxybenzyl pyrimidin-2'-yl)imino-1'-(5-methylisatinyl)]methyl]-N 1-piperazinyl]-3-quinoline carboxylic acid ( 10) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV, HCV, Mycobacterium tuberculosis and various pathogenic bacteria.