AIDS-defining Opportunistic Infection Research Articles

Impact of HIV status on prognosis of malignancies among people living with HIV in Japan.

Antiretroviral therapy has reduced the incidence and mortality of AIDS-defining malignancies (ADM); however, non-AIDS-defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS-defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS-defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T-cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5-year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS-defining opportunistic infections after receiving chemotherapy.

Cytomegalovirus retinitis and antiretroviral treatment: A fifteen year experience.

BackgroundSouth Africa’s public antiretroviral treatment (ART) programme has undergone progressive changes since its introduction in 2004. The effect of this on the burden of the AIDS-defining opportunistic infection, cytomegalovirus retinitis (CMVR), in SA, has not been fully appreciated.ObjectivesTo determine the effect of ART availability in the public sector of SA on the trend in the number of cases of newly diagnosed CMVR over time.MethodsThis is a retrospective study from 01 November 2002 to 31 August 2017 that took place at a tertiary hospital in the KwaZulu-Natal (KZN) province.ResultsA total of 383 participants were included in the study, with 60.1% being female and 94% of black African origin. The mean age of patients was 34.08 years (SD ± 7.24). A linear trend model suggested an overall linear decrease in the number of new cases of CMVR per year (R2 of 0.67). The average number of new cases of CMVR per year prior to ART being available to all persons living with HIV (PLWH) with a CD4+ ≤ 350 cells/μL and after was 34 and 13, respectively, and the difference (61.76%) between these values was statistically significant, P = 0.001. The median CD4+ count at diagnosis of CMVR was 22 (interquartile range: 9–51.25) cells/μL. An overall 51% of patients in this study were on ART at diagnosis of CMVR. There was a higher proportion of patients on ART ≤ 6 months (63.3%), compared with those on ART > 6 months (36.7%), and the difference was statistically significant, P < 0.01.ConclusionART has resulted in a decrease in the burden of CMVR on ophthalmic services for many in KZN, particularly following the introduction of ART for all PLWH with a CD4 ≤ 350 cells/μL.

Spectrum of AIDS-defining Opportunistic Infections among Anti-retroviral treatment-naïve HIV-seropositive Cases in Northeast India

This is Letter to the Editor

Gastrointestinal disseminated histoplasmosis in HIV-infected patients: A descriptive and comparative study.

Disseminated histoplasmosis is one the main AIDS-defining opportunistic infections in HIV-infected patients, notably in Latin America. The non-specific and proteiform clinical presentation leads to diagnostic delays that may lead to fatal outcomes. This retrospective multicentric study aimed to describe the frequency and manifestations of gastrointestinal histoplasmosis in French Guiana, and to compare patients with disseminated histoplasmosis with or without gastrointestinal involvement.Between January 1, 1981 and October 1, 2014 co-infections with HIV and histoplasmosis were enrolled. Inclusion criteria were: age >18 years, confirmed HIV infection; first proven episode of histoplasmosis.Among 349 cases of disseminated histoplasmosis, 245 (70%) had a gastrointestinal presentation. Half of patients with gastrointestinal signs had abdominal pain or diarrhea, mostly watery. Half of patients with abdominal pain had diarrhea (63/124) and half of those with diarrhea (63/123) had abdominal pain. A significant proportion of patients also had hepatomegaly and, to a lesser degree, splenomegaly. After adjusting for potential confounding, the presence of lymphadenopathies >2cm (AOR = 0.2, IC95 = 0.04–0.7, P = 0.01), Haitian origin (AOR = 0.04, IC95 = 0.004–0.4, P = 0.006) were associated with a lower prevalence of gastrointestinal signs and positive gastrointestinal presence of H. capsulatum. Persons with a gastrointestinal H. capsulatum were more likely to have a decreased prothrombin time, lower ferritin, lower liver enzymes, and lower concentrations of LDH than those without gastrointestinal signs and symptoms. They also had a shorter interval between symptoms onset and diagnosis. Patients with a positive gastrointestinal identification of H. capsulatum were less likely to die at 1 month than those without a gastrointestinal presentation (respectively, 4.6% vs 18.5%, P = 0.01).Subacute or chronic gastrointestinal presentations are very frequent during disseminated histoplasmosis, they seem less severe, and should lead to suspect the diagnosis in endemic areas. There were populational or geographic differences in the frequency of gastrointestinal manifestations that could not be explained.

Getting Histoplasmosis on the Map of International Recommendations for Patients with Advanced HIV Disease.

Progressive disseminated histoplasmosis, caused by H. capsulatum, is a life-threatening illness and is an AIDS-defining opportunistic infection. It is neglected, worryingly under-diagnosed, and often misdiagnosed as cancer or tuberculosis with fatal consequences. Globally, over 100,000 cases of disseminated histoplasmosis have been estimated. In 2017, the World Health Organization (WHO) noted that disseminated histoplasmosis is a significant cause of mortality in AIDS patients. Through the rigorous efforts of the Global Action Fund for Fungal Infections (GAFFI) and partners, in 2019, the Histoplasma antigen test was included on the 2nd Edition of the WHO List of Essential Diagnostics. The drugs used in the treatment of histoplasmosis (amphotericin B and itraconazole) are on the WHO Essential Medicine List. The Manaus Declaration on histoplasmosis in the Americas and the Caribbean, where histoplasmosis kills more people with HIV than tuberculosis, advocates for universal access to rapid testing for histoplasmosis and availability of essential drugs for the treatment of histoplasmosis in every country by 2025. Hyperendemic areas are present in the Americas, Caribbean, Southeast Asia, and Latin America. In conclusion, histoplasmosis remains an important clinical and public health problem. To reduce HIV-associated mortality, disseminated histoplasmosis must be addressed through advocacy, increased awareness, and universal access to essential diagnostics and antifungal agents.

Trends in Mortality From Human Immunodeficiency Virus Infection, 1984-2016: An Autopsy-Based Study.

With increasing use and efficacy of antiretroviral therapy for human immunodeficiency virus (HIV) infection, deaths from acquired immunodeficiency syndrome (AIDS)-defining conditions have decreased. To examine trends in the cause of death of HIV-infected patients who underwent autopsy at a major New York City hospital from 1984 to 2016, a period including the major epochs of the AIDS epidemic. Retrospective review of autopsy records and charts with modeling of trends by logistic regression using polynomial models. We identified 252 autopsies in adult patients with AIDS (by 1982 definition) or HIV infection. Prior to widespread use of highly active antiretroviral therapy, in 1984-1995, on average 13 autopsies per year were done. Post-highly active antiretroviral therapy, the average number of autopsies declined to 4.5 per year. The fitted mean age at death was 35 years in 1984 and increased curvilinearly to 46 years (95% CI, 43-49) in 2016 (P < .001). By regression analysis, mean CD4+ T-cell count increased from 6 in 1992 to 64 in 2016 (P = .01). The proportion of AIDS-defining opportunistic infections decreased, from 79% in 1984-1987 to 41% in 2008-2011 and 29% in 2012-2016 (P = .04). The frequency of nonopportunistic infections, however, increased from 37% in 1984-1987 to 73% in 2008-2011 and 57% in 2012-2016 (P = .001). The frequency of AIDS-defining and other malignancies did not change significantly during the study period. The prevalence of atherosclerosis at autopsy rose dramatically, from 21% in 1988-1991 to 54% in 2008-2011 (P < .001). Despite limitations of autopsy studies, many trends in the evolution of the HIV/AIDS epidemic are readily discernable.

Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial

Thai patients with HIV have higher exposure to HIV protease inhibitors than do white people and dose reduction might be possible. We compared the efficacy of low-dose with standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai patients with HIV. In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years or older who were receiving ritonavir-boosted protease-inhibitor-based antiretroviral therapy (ART) with HIV plasma viral loads of less than 50 copies per mL, an alanine aminotransferase concentration of less than 200 IU/L, and a creatinine clearance of at least 60 mL/min from 14 hospitals in Thailand. We excluded patients who had active AIDS-defining disease or opportunistic infections, had a history of an HIV viral load of 1000 copies per mL or more after 24 weeks of any ritonavir-boosted protease-inhibitor-based ART, used concomitant medications that could interact with the study drugs, were pregnant or lactating, had illnesses that might change the effect of the study drugs, or had a history of sensitivity to the study drugs. A biostatistician at the study coordinating centre randomly allocated patients (1:1) to switch the protease inhibitor for oral atazanavir 200 mg and ritonavir 100 mg or for atazanavir 300 mg and ritonavir 100 mg once daily, both with two nucleoside or nucleotide reverse transcriptase inhibitors at recommended doses. Randomisation was done with a minimisation schedule, stratified by recruiting centre, use of tenofovir, and use of indinavir as a component of the preswitch regimen. The primary endpoint was the proportion of patients with viral loads of less than 200 copies per mL at week 48, and we followed up patients every 12 weeks. Treatments were open label, the non-inferiority margin was -10%, and all patients who received at least one dose of study medication were analysed. This trial is registered with ClinicalTrials.gov, number NCT01159223. Between July 6, 2011, and Dec 23, 2013, we randomly assigned 559 patients: 279 to receive atazanavir 200 mg and ritonavir 100 mg (low dose) and 280 to atazanavir 300 mg and ritonavir 100 mg (standard dose). At week 48, 265 (97·1%) of 273 in the low-dose group and 267 (96·4%) of 277 in the standard-dose group had viral loads of less than 200 copies per mL (difference 0·68; 95% CI -2·29 to 3·65). Seven (3%) of 273 in the low-dose group and 21 (8%) of 277 in the standard-dose group discontinued their assigned treatment (p=0·01). 46 (17%) of 273 participants in the low-dose group and 97 (35%) of 277 in the standard-dose group had total bilirubin grade 3 or higher toxicity (≥3·12 mg/dL; p<0·0001). A switch to low-dose atazanavir should be recommended for Thai patients with well controlled HIV viraemia while on regimens based on boosted protease inhibitors. The National Health Security Office and Kirby Institute for Infection and Immunity in Society.

Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000-2010.

There are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in care in the United States and Canada. We studied HIV-infected participants in 16 cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) during 2000-2010. After excluding 16 737 (21%) with any AIDS-defining clinical events documented before NA-ACCORD enrollment, we analyzed incident OIs among the remaining 63 541 persons, most of whom received antiretroviral therapy during the observation. We calculated incidence rates per 100 person-years of observation (hereafter, "person-years") with 95% confidence intervals (CIs) for the first occurrence of any OI and select individual OIs during 2000-2003, 2004-2007, and 2008-2010. A total of 63 541 persons contributed 261 573 person-years, of whom 5836 (9%) developed at least 1 OI. The incidence rate of any first OI decreased over the 3 observation periods, with 3.0 cases, 2.4 cases, and 1.5 cases per 100 person-years of observation during 2000-2003, 2004-2007, and 2008-2010, respectively (Ptrend<.001); the rates of most individual OIs decreased as well. During 2008-2010, the leading OIs included Pneumocystis jiroveci pneumonia, esophageal candidiasis, and disseminated Mycobacterium avium complex or Mycobacterium kansasii infection. For HIV-infected persons in care during 2000-2010, rates of first OI were relatively low and generally declined over this time.

Pneumocystis jirovecii Pneumonia in Human Immunodeficiency Virus Infection.

The presentation of Pneumocystis pneumonia (PCP) in previously healthy men having sex with men (MSM) in San Francisco and New York City in 1981 heralded the beginning of the human immunodeficiency virus (HIV) pandemic. Despite a decreasing incidence of PCP among patients with HIV/AIDS (acquired immunodeficiency syndrome) since the advent of combination antiretroviral therapy in the mid-1990s, PCP remains one of the most common AIDS-defining opportunistic infections in the United States and Western Europe. Newer molecular diagnostic tests in conjunction with standard immunofluorescent or colorimetric tests have allowed for more rapid and accurate diagnosis. Although several effective oral and intravenous therapies exist to treat PCP, mortality rates in HIV-infected individuals remain unacceptably high, especially in those with advanced AIDS. The identification of specific mutations in Pneumocystis genes targeted by trimethoprim-sulfamethoxazole has raised concerns about the development of resistance to the drug of choice and may ultimately lead to greater utilization of alternative therapies to treat PCP in the future.

Incidence of AIDS-Defining Opportunistic Infections and Mortality during Antiretroviral Therapy in a Cohort of Adult HIV-Infected Individuals in Hanoi, 2007-2014.

BackgroundAlthough the prognosis for HIV-infected individuals has improved after antiretroviral therapy (ART) scale-up, limited data exist on the incidence of AIDS-defining opportunistic infections (ADIs) and mortality during ART in resource-limited settings.MethodsHIV-infected adults in two large hospitals in urban Hanoi were enrolled to the prospective cohort, from October 2007 through December 2013. Those who started ART less than one year before enrollment were assigned to the survival analysis. Data on ART history and ADIs were collected retrospectively at enrollment and followed-up prospectively until April 2014.ResultsOf 2,070 cohort participants, 1,197 were eligible for analysis and provided 3,446 person-years (PYs) of being on ART. Overall, 161 ADIs episodes were noted at a median of 3.20 months after ART initiation (range 0.03–75.8) with an incidence 46.7/1,000 PYs (95% confidence interval [CI] 39.8–54.5). The most common ADI was tuberculosis with an incidence of 29.9/1,000 PYs. Mortality after ART initiation was 8.68/1,000 PYs and 45% (19/45) died of AIDS-related illnesses. Age over 50 years at ART initiation was significantly associated with shorter survival after controlling for baseline CD4 count, but neither having injection drug use (IDU) history nor previous ADIs were associated with poor survival. Semi-competing risks analysis in 951 patients without ADIs history prior to ART showed those who developed ADIs after starting ART were at higher risk of death in the first six months than after six months.ConclusionADIs were not rare in spite of being on effective ART. Age over 50 years, but not IDU history, was associated with shorter survival in the cohort. This study provides in-depth data on the prognosis of patients on ART in Vietnam during the first decade of ART scale-up.

Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000–2010

Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000–2010

Effect of subsequent pregnancies on HIV disease progression among women in the Mulago Hospital MTCT-Plus program in Uganda

To investigate the effect of subsequent pregnancies on HIV disease progression among HIV-infected women at Mulago Hospital, Uganda. In a retrospective cohort study, data were analyzed from women enrolled in the Mother-To-Child Transmission Plus program from March 2003 to December 2011. The CD4 cell count, the development of new AIDS-defining opportunistic infections, and the AIDS-related mortality were compared between women with and without subsequent pregnancies. Overall, 409 women were enrolled and 195 (47.7%) had subsequent pregnancies. Antiretroviral therapy (ART) was initiated in 143 (73.3%) women with and 155 (72.4%) women without subsequent pregnancies. Kaplan-Meier analysis for women receiving ART showed no differences between women with and without subsequent pregnancies in the median times to clinical failure (62.7 vs 64.7 months; P=0.31), immunological failure (68.8 vs 75.5 months; P=0.10), and death (68.8 vs 75.5 months; P=0.53). In a Cox regression analysis, subsequent pregnancies were not associated with immunological failure during follow-up (adjusted hazard ratio 1.13, 95% confidence interval 0.06-2.09). Subsequent pregnancies could have no detrimental effect on HIV disease progression among HIV-infected women whose treatment is well managed.

Tropical and travel-related dermatomycoses : Part 2: cutaneous infections due to yeasts, moulds, and dimorphic fungi

Besides dermatophytoses, a broad range of cutaneous infections due to yeasts and moulds may occur in subtropical and tropical countries where they can affect travellers. Not to be forgotten are endemic occurring dimorphic or biphasic fungi in countries with hot climate, which cause systemic and secondary cutaneous infections in immunosuppressed and immunocompetent people. In the tropics, the prevalence of pityriasis versicolor, caused by the lipophilic yeast Malassezia spp., is about 30-40 %, in distinct areas even 50 %. Increased hyperhidrosis under tropical conditions and simultaneously humidity congestion have to be considered as significant disposing factors for pityriasis versicolor. In tropical countries, therefore, an exacerbation of a preexisting pityriasis versicolor in travellers is not rare. Today, mostly genital yeast infections due to the new species Candida africana can be found worldwide. Due to migration from Africa this yeast pathogen has reached Germany and Europe. Eumycetomas due to mould fungi are rarely diagnosed in Europe. These deep cutaneous mould infections are only found in immigrants from African countries. The therapy of eumycetoma is protracted and often not successful. Cutaneous cryptococcoses due to the yeast species Cryptococcus neoformans and Cryptococcus gattii occur worldwide; however, they are found more frequently in the tropics. Immunosuppressed patients, especially those with HIV/AIDS, are affected by cryptococcoses. Furthermore, Cryptococcus gattii also causes infections in immunocompetent hosts in Central Africa, Australia, California, and Central America.Rarely found are infections due to dimorphic fungi after travel to countries where these fungal pathogens are endemic. In individual cases, cutaneous or lymphogenic transferred sporotrichosis due to Sporothrix schenkii can occur. Furthermore, scarcely known is secondary cutaneous coccidioidomycosis due to Coccidioides immitis after travelling to desert-like endemic regions in southwestern states of the United States and in Latin America, where primary respiratory infection due to this biphasic fungus can be acquired. The antifungal agent itraconazole is the treatment of choice for sporotrichosis and coccidioidomycosis. Talaromyces marneffei-until recently known as Penicillium marneffei-is only found in Southeastern Asia. Mycosis due to this dimorphic fungus has to be considered as an AIDS-defining opportunistic infection. After hematogeneous spread, Talaromyces marneffei affects the skin and mucous membranes of the mouth. Amphotericin B and itraconazole can be used for therapy.

Deep Vein Thrombosis Following Enteric Fever &amp; Immunological Failure in HIV Positive Soldier: Case Report

Incidence of deep vein thrombosis (DVT) is 2–10 times more in human immunodeficiency virus (HIV)-infected persons than non-HIV cohort. Risk factors involved with DVT in HIV-infected patients are age older than 45 years, use of protease inhibitor in highly active antiretroviral therapy (ART), most common indinavir, hospitalization and presence of AIDS-defining opportunistic infections such as cytomegalovirus, Pneumocystis jiroveci (is a yeast like fungus particularly in immune-compromised host), and Mycobacterium-intracellular. Others well known thrombogenic risk factors include are such as immobility, cigarette smoking, advanced age, pregnancy, pelvic surgery, and personal or family history of DVT may be absent in HIV-infected patients presenting with DVT. Inflammation and venous thrombosis are related to each other, and the associations between them are strong when the inflammation or the infection has occurred recently, or the inflammation is active. A 29-year-old HIV-positive soldier on first line ART with poor adherence presented with fever pain abdomen and diarrhea and was diagnosed to have an enteric fever with immunological and clinical failure. He was treated for enteric fever but during treatment of enteric fever he complains of painful left lower limb swelling after 4 weeks and was suspect to have DVT of left lower limb based on Doppler studies. After confirmation of DVT by Doppler images, thrombolytic therapy was started, and gradually improvement was seen in the condition. Recent Infection or inflammation has a strong association with the development of thrombosis in HIV-positive patients, absent with classical predisposing factors of DVT. Physicians involved in the care of HIV-positive patients should be aware of this condition and the associated aggravating risk factors in them so as to provide timely management.

AIDS defining opportunistic infections in patients with high CD4 counts in the combination antiretroviral therapy (cART) era: things ain't what they used to be

IntroductionAccording to reports from observational databases, classic AIDS-defining opportunistic infections (ADOIs) occur in patients with CD4 counts above 500/µL on and off cART. Adjudication of these events is usually not performed. However, ADOIs are often used as endpoints, for example, in analyses on when to start cART.Materials and MethodsIn the database, Swiss HIV Cohort Study (SHCS) database, we identified 91 cases of ADOIs that occurred from 1996 onwards in patients with the nearest CD4 count >500/µL. Cases of tuberculosis and recurrent bacterial pneumonia were excluded as they also occur in non-immunocompromised patients. Chart review was performed in 82 cases, and in 50 cases we identified CD4 counts within six months before until one month after ADOI and had chart review material to allow an in-depth review. In these 50 cases, we assessed whether (1) the ADOI fulfilled the SHCS diagnostic criteria (www.shcs.ch), and (2) HIV infection with CD4 >500/µL was the main immune-compromising condition to cause the ADOI. Adjudication of cases was done by two experienced clinicians who had to agree on the interpretation.ResultsMore than 13,000 participants were followed in SHCS in the period of interest. Twenty-four (48%) of the chart-reviewed 50 patients with ADOI and CD4 >500/µL had an HIV RNA <400 copies/mL at the time of ADOI. In the 50 cases, candida oesophagitis was the most frequent ADOI in 30 patients (60%) followed by pneumocystis pneumonia and chronic ulcerative HSV disease (Table 1). Overall chronic HIV infection with a CD4 count >500/µL was the likely explanation for the ADOI in only seven cases (14%). Other reasons (Table 1) were ADOIs occurring during primary HIV infection in 5 (10%) cases, unmasking IRIS in 1 (2%) case, chronic HIV infection with CD4 counts <500/µL near the ADOI in 13 (26%) cases, diagnosis not according to SHCS diagnostic criteria in 7 (14%) cases and most importantly other additional immune-compromising conditions such as immunosuppressive drugs in 14 (34%). ConclusionsIn patients with CD4 counts >500/ µL, chronic HIV infection is the cause of ADOIs in only a minority of cases. Other immuno-compromising conditions are more likely explanations in one-third of the patients, especially in cases of candida oesophagitis. ADOIs in HIV patients with high CD4 counts should be used as endpoints only with much caution in studies based on observational databases.

CD4+ cell count recovery in naïve patients initiating cART, who achieved and maintained plasma HIV-RNA suppression.

IntroductionA key objective of combined antiretroviral therapy (cART) is to reach and maintain high CD4 cell counts to provide long-term protection against AIDS-defining opportunistic infections and malignancies, as well as other comorbidities. However, a high proportion of patients present late for care. Our objective was to assess CD4 cell count recovery up to seven years in naïve patients initiating cART with at least three drugs in usual clinical care.MethodsFrom the French Hospital Database on HIV, we selected naïve individuals initiating cART from 2000 with at least two years of follow-up. Participants were further required to have achieved viral load suppression by six months after initiating cART and were censored in case of virological failure. We calculated the proportion of patients (Kaplan-Meier estimates) who achieved CD4 recovery to >500/mm3 according to baseline CD4 cell count.ResultsA total of 15,025 patients were analyzed with a median follow-up on ART of 65.5 months (IQR: 42.3–96.0). At cART initiation, the median age was 38.6 years (IQR: 32.2–46.0), 9734 (64.8%) were men, median CD4 cell count was 239 (IQR: 130–336) and 2668 (17.8%) had a prior AIDS event. Results are presented in the Table 1.ConclusionsThis study shows that CD4 cell counts continue to increase seven years after cART initiation, whatever the baseline CD4 cell count. Failing to achieve CD4 recovery with continuous viral load suppression is rare for naïve patients initiating cART in routine clinical practice, but takes substantially longer in patients who initiate antiretroviral therapy at low CD4 cell counts.

Oral Candidiasis: An Opportunistic Infection of AIDS

Copyright: © 2014 Jabra-Rizk MA. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Candida albicans (C. albicans) is an opportunistic fungal species commonly colonizing human mucosal surfaces. However, when host defenses are weakened, C. albicans can proliferate causing an array of infections ranging from mucosal to systemic infections that are often life-threatening. Specifically, oral candidiasis is considered an AIDSdefining opportunistic infection with up to 80% of HIV+ individuals suffering recurrent episodes during the course of their HIV disease progression. As a dimorphic microbial species, C. albicans is capable of switching morphology between yeast and hyphal forms. Where the yeast form is responsible for systemic disease, hyphae are invasive filaments and therefore are adept at causing mucosal infections. The mouse model is the most suitable animal model to study the development of oral candidiasis due to the similarity to the disease process in humans. (A) Following anesthesia, animals are infected sublingually using swabs saturated with C. albicans cell suspensions. (B) Five days post-infection, white lesions are seen on tongue surface rapidly developing into overt candidiasis characterized by white plaques covering the tongue and other oral surfaces. In order to visualize the process of tissue invasion by C. albicans, animals are euthanized and the tongues are harvested and subjected to histopathology analysis where tongue tissue are embedded in paraffin, sectioned and stained with Periodic Acid Schiff stain then examined by light microscopy. (C) Microscopic images of tissue sections demonstrate the extensive presence and penetration of epithelial tissue by the invasive C. albicans hyphae (white arrows) with massive influx of host immune cells (yellow arrows). Tongues were also subjected to scanning electron microscopy analysis. (D) Magnified (5000x) images of the tongue surface demonstrate penetration of hyphae from the sublingual area where C. albicans is inoculated leaving sizable gaps at sites of emergence of the hyphae through the tongue surface (red arrows). This extensive tissue invasive process by C. albicans hyphal elements is manifested clinically as white lesions characterizing oral candidiasis. A

Re: Spectrum of AIDS Defining Opportunistic Infections in a Series of 77 Hospitalised HIV-Infected Omani Patients

Sir, The recent report on the spectrum of AIDS-defining opportunistic infections (OIs) in HIV-infected patients is very interesting.1 Balkhair et al. concluded that “a wide spectrum of OIs are seen in hospitalised HIV-infected patients in Oman.”1 Indeed, OIs are common in HIV and can be seen elsewhere around the world. The concern with the present cohort study is the diagnostic approach. Certainly, to identify the clinical spectrum, good, systematic and highly accurate tests must be implemented. Some OIs require special tests for detection. Focusing on the present report, an interesting point is the low prevalence of intestinal OIs. This might be due to these types of OIs having been overlooked. In our experience, several intestinal parasites including OIs are common and must be screened for in HIV-infected patients.2–3

Successfully treated HIV-infected patients have differential expression of NK cell receptors (NKp46 and NKp30) according to AIDS status at presentation

Differences in innate immune responses may be associated with different capabilities of controlling HIV infection, not necessarily reflected by CD4+ T-cell counts alone. We investigated by cytofluorometry the expression of NK cell receptors and ligands in 19 treated HIV-infected patients with CD4+<220ml–1 at presentation (11 AIDS, 8 non-AIDS) and 10 healthy donors. Expression of NKp46 and NKp30 was significantly higher in non-AIDS vs. AIDS patients. Overall, the level of NKp46 expression directly correlated with the degree of NK cell cytotoxicity. As compared to healthy donors, in both groups, there was a similar increase of CD69 and HLA-DR expression in NK cells that directly correlated with the presence of activation markers (HLA-DR) on CD4+ and CD8+ T cells. As compared to AIDS, in non-AIDS patients in vitro activated CD4+ showed higher expression of MIC-A (NKG2D ligand), with significantly higher Nectin-2/DNAM-1 and MIC-A/NKG2D ratios. Thus, NK cell responses in AIDS and non-AIDS patients with similar CD4+ counts significantly differ despite similar treatment. This suggests an involvement of innate mechanisms, in preventing AIDS-defining opportunistic infections in HIV infection and further suggests, that CD4+ absolute counts alone, may be inadequate to explain differences in the clinical outcome.

Current laboratory diagnosis of opportunistic enteric parasites in human immunodeficiency virus-infected patients

Diarrhea is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. Opportunistic enteric parasitic infections are encountered in 30-60% of HIV seropositive patients in developed countries and in 90% of patients in developing countries. Once the CD4+ cell count drops below 200 cells/μl, patients are considered to have developed acquired immunodeficiency syndrome (AIDS), with the risk of an AIDS-defining illness or opportunistic infection significantly increasing. Opportunistic enteric parasites encountered in these patients are Cryptosporidium, Isospora, Cyclospora, and microsporidia; as well as those more commonly associated with gastrointestinal disease, for example, Giardia intestinalis, Entamoeba histolytica, Strongyloides stercoralis, and also rarely Balantidium coli. In view of AIDS explosion in India, opportunistic enteric parasites are becoming increasingly important and it has to be identified properly. Apart from wet mounts, concentration methods for stool samples and special staining techniques for identification of these parasites, commercially available fecal immunoassays are widely available for the majority of enteric protozoa. Molecular methods such as polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, flow cytometry, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), have also come in the pipeline for early diagnosis of these infections. Proper disposal of the feces to prevent contamination of the soil and water, boiling/filtering drinking water along with improved personal hygiene might go a long way in preventing these enteric parasitic infections.