AIDS-defining Disease Research Articles

Immune recovery in HIV-infected patients after Candida esophagitis is impaired despite long-term antiretroviral therapy.

Objective:Candida esophagitis belongs to the most common AIDS-defining diseases; however, a comprehensive immune pathogenic concept is lacking.Design:We investigated the immune status of 37 HIV-1-infected patients from the Swiss HIV cohort study at diagnosis of Candida esophagitis, 1 year before, 1 year later and after 2 years of suppressed HIV RNA. We compared these patients with three groups: 37 HIV-1-infected patients without Candida esophagitis but similar CD4+ cell counts as the patients at diagnosis (advanced HIV group), 15 HIV-1-infected patients with CD4+ cell counts higher than 500 cells/μl, CD4+ cell nadirs higher than 350 cells/μl and suppressed HIV RNA under combination antiretroviral therapy (cART) (early cART group) and 20 healthy individuals.Methods:We investigated phenotype, cytokine production and proliferative capacity of different immune cells by flow cytometry and enzyme-linked immunosorbent spot.Results:We found that patients with Candida esophagitis had nearly abolished CD4+ cell proliferation in response to Candida albicans, significantly increased percentages of dysfunctional CD4+ cells, significantly decreased cytotoxic natural killer cell counts and peripheral innate lymphoid cell counts and significantly reduced IFN-γ and IL-17 production compared with the early cART group and healthy individuals. Most of these defects remained for more than 2 years despite viral suppression. The advanced HIV group without opportunistic infection showed partly improved immune recovery.Conclusion:Our data indicate that Candida esophagitis in HIV-1-infected patients is caused by an accumulation of multiple, partly Candida-specific immunological defects. Long-term immune recovery is impaired, illustrating that specific immunological gaps persist despite cART. These data also support the rationale for early cART initiation to prevent irreversible immune defects.

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.

CD8 T cells mediate polyomavirus-associated CNS demyelination

Abstract JC polyomavirus (JCV), a common member of the virome in healthy humans, can cause the frequently fatal brain demyelinating disease Progressive Multifocal Leukoencephalopathy (PML) in immunocompromised individuals. PML, a pre-HAART AIDS-defining disease, has reemerged and is increasing in incidence in patients receiving immunodulatory therapies for autoimmune and inflammatory disorders. Lack of an animal model has hampered understanding of PML pathogenesis. We have developed a novel mouse model using intracerebral (i.c.) inoculation of mouse polyomavirus (MPyV), which mimics JCV-associated demyelination and shows similar histological features to PML. By one month after MPyV inoculation, C57BL/6 mice develop diffuse subcortical white matter demyelination, predominantly in the corpus callosum. Diffusion tensor magnetic resonance imaging in infected mice reveals severe peri-ventricular edema and a loss of structural integrity predominately in the corpus callosum and caudate. Virus-specific CD8 T cells robustly infiltrate the CNS and are stably maintained after CNS entry. Antibody-mediated depletion of CD4 and CD8 T cells prior to infection abrogates demyelination in the corpus callosum, despite resulting in a 50–100 fold increase in virus levels. Additionally, CD8 T cell-depletion alone was sufficient to cause higher virus levels in the brain. MPyV was controlled in the absence of CD4 T cells; however, MPyV-specific CD8 T cells in CD4 T cell-deficient mice expressed lower levels of CD103 (aE integrin), which binds epithelial E-cadherin. These data demonstrate that CD8 T cells infiltrating the CNS of MPyV-infected mice play a major role in this demyelinating leukoencephalitis.

ПІДВИЩЕННЯ ІМУНОЛОГІЧНОЇ ЕФЕКТИВНОСТІ ВИСОКОАКТИВНОЇ АНТИРЕТРОВІРУСНОЇ ТЕРАПІЇ У ХВОРИХ НА ВІЛ-ІНФЕКЦІЮ ЗА ДОПОМОГОЮ ЕНТЕРОСОРБЦІЇ

&lt;p&gt;Метою дослідження була оцінка впливу комбіно-&lt;br /&gt;ваного застосування ВААРТ і кремнійорганічного ен-&lt;br /&gt;теросорбенту «Атоксил» на динаміку імунологічних&lt;br /&gt;показників у хворих з ВІЛ-інфекцією. В дослідження&lt;br /&gt;було включено 39 хворих з IV клінічною стадією ВІЛ-&lt;br /&gt;інфекції, які були рандомізовані на дві групи: перша&lt;br /&gt;група – 19 хворих, які отримували ВААРТ і ентеросор-&lt;br /&gt;бент «Атоксил», друга – 20 хворих, які отримували&lt;br /&gt;лише ВААРТ. Середній вміст CD4-лімфоцитів склав&lt;br /&gt;79 (14-270) у мкл в першій групі і 87 (51-205) у мкл в&lt;br /&gt;другій. У 93 % хворих мали місце опортуністичні та&lt;br /&gt;СНІД-індикаторні захворювання, серед яких превалю-&lt;br /&gt;вав туберкульоз (80 %). Усім хворим була призначена&lt;br /&gt;ВААРТ за схемою AZT+3TC+EFV. Через 6 міс. лікування&lt;br /&gt;рівень HIV-RNA-1 в плазмі крові не визначався в 95 %&lt;br /&gt;пацієнтів обох груп. У першій групі хворих абсолютна&lt;br /&gt;кількість CD4-лімфоцитів за 6 міс. ВААРТ підвищи-&lt;br /&gt;лася до 201 (179-302) на мкл, і була більше (р&amp;lt;0,05),&lt;br /&gt;ніж в другій групі (159 (52-198)). Таким чином, через&lt;br /&gt;6 міс. ВААРТ у першій групі хворих, які додатково&lt;br /&gt;отримували кремнійорганічний ентеросорбент,&lt;br /&gt;середній приріст кількості CD4-лімфоцитів був на&lt;br /&gt;70 % вище, ніж у другій групі, яка отримувала лише&lt;br /&gt;ВААРТ, з однаковою вірусологічною ефективністю&lt;br /&gt;противірусного лікування.&lt;br /&gt;Ключові слова: ВІЛ-інфекція, ентеросорбент,&lt;br /&gt;ВААРТ, CD4-лімфоцит, мікробна транслокація, імунна&lt;br /&gt;активація.&lt;/p&gt;

High Mortality of Disseminated Non-Tuberculous Mycobacterial Infection in HIV-Infected Patients in the Antiretroviral Therapy Era.

BackgroundLittle information is available on the mortality and risk factors associated with death in disseminated non-tuberculous mycobacterial infection (dNTM) in HIV-infected patients in the ART-era.MethodsIn a single-center study, HIV-infected dNTM with positive NTM culture from sterile sites between 2000 and 2013 were analysed. The clinical characteristics at commencement of anti-mycobacterial treatment (baseline) were compared between those who survived and died.ResultsTwenty-four patients were analyzed. [The median CD4 27/μL (range 2–185)]. Mycobacterium avium and M. intracellulare accounted for 20 (83%) and 3 (13%) of isolated NTM. NTM bacteremia was diagnosed in 15 (63%) patients. Seven (29%) patients died, and NTM bacteremia was significantly associated with mortality (p = 0.022). The baseline CD4 count was significantly lower in the non-survivors than the survivors (median 7/μL versus 49, p = 0.034). Concomitant AIDS-defining diseases or malignancies were not associated with mortality. Immune-reconstitution syndrome (IRS) occurred to 19 (79%) patients (8 paradoxical and 11 unmasking), and prognosis tended to be better in unmasking-IRS than the other patients (n = 13) (p = 0.078). Patients with paradoxical-IRS had marginally lower CD4 count and higher frequency of bacteremia than those with unmasking-IRS (p = 0.051, and 0.059). Treatment with systemic corticosteroids was applied in 63% and 55% of patients with paradoxical and unmasking-IRS, respectively.ConclusiondNTM in HIV-infected patients resulted in high mortality even in the ART-era. NTM bacteremia and low CD4 count were risk factors for death, whereas patients presented with unmasking-IRS had marginally better prognosis. IRS occurred in 79% of the patients, suggesting difficulty in the management of dNTM.

Noninfectious and Nonneoplastic Conditions Associated with Human Immunodeficiency Virus Infection.

The goal of this review is to describe evolving epidemiology of noninfectious, nonneoplastic pulmonary complications of HIV infection, including HIV-associated pulmonary arterial hypertension (HIV-PAH) and interstitial lung disease (ILD). The development of antiretroviral therapy has rendered HIV a chronic illness in treated patients, and the landscape of HIV-associated medical conditions continues to evolve. Although there has been a shift away from AIDS-defining infectious diseases and malignancies, HIV-PAH continues to affect survival adversely when compared with HIV-infected patients without PAH. Studies of pre- and post-highly active antiretroviral therapy (HAART) era show that the prevalence of HIV-PAH remains high and unchanged. The increased prevalence of PAH among HIV-infected individuals has led to several complementary theories about potential mechanisms underlying this disease. Unique mechanisms of HIV-PAH focus on direct effects of viral proteins; alterations in cellular immunologic/inflammatory reactions to the virus; additive effects of cocaine, heroin, and other drugs of abuse; and potentially toxic aspects of antiretroviral and associated therapies. PAH-specific therapy with HAART is likely beneficial in the treatment of HIV-PAH patients. The prevalence of ILD in HIV-infected individuals is also significantly higher than that in the general population. Lymphoid interstitial pneumonitis (LIP) and nonspecific interstitial pneumonia (NSIP) have been reported in both HIV-infected children and adults, and NSIP is more common than LIP in HIV-infected patients. At present, there is no consensus on the pathogenesis of LIP and NSIP in HIV. Finally, we briefly review the literature on venous thromboembolic disease in HIV-infected individuals.

Kaposi sarcoma in HIV-seronegative children presenting to the paediatric oncology ward in The Queen Elizabeth Central Hospital, Blantyre, Malawi during 2002-2014.

One of the most common malignancies in HIV-endemic, resource-poor countries is Kaposi sarcoma (KS). It is an AIDS-defining disease and as Malawi's incidence and prevalence of HIV is high, KS is now the most common cancer in adult male Malawians and the second most common in women and children. Most attention has focused on HIV-seropositive adults as their number far outweighs those of children. This audit concerns the presentation and outcome of HIV-seronegative children with KS who presented in a 12-year period (2002-2014) to The Queen Elizabeth Central Hospital. Twenty (10.5%) of the 191 children with KS presenting to the paediatric oncology ward during 2002-2014 were HIV-seronegative. They were usually younger than seropositive children and 62% had severe anaemia. The main presenting complaints in the HIV-seronegative group were woody oedema, commonly of a limb, and lymphadenopathy. Woody oedema was common in children with or without HIV infection. Seronegative children with KS were less likely to have oral KS than HIV infected children. Of 11 children who completed courses of chemotherapy, seven (63%) had complete cure sustained over a 1-year follow-up period. KS is potentially curable in this group of children. Chemotherapy regimens are equally effective in HIV-seropositive and HIV-seronegative children. The presentation of HIV-seronegative children with KS differs from adults and HIV-seropositive children. Further research is necessary to determine possible triggers for developing KS in HIV-seronegative children.

What Triggers a Diagnosis of HIV Infection in the Tokyo Metropolitan Area? Implications for Preventing the Spread of HIV Infection in Japan.

BackgroundJapan has not succeeded in reducing the annual number of new HIV-infected patients, although the prevalence of HIV infection is low (0.02%).MethodsA single-center observational study was conducted at the largest HIV clinic in Tokyo, which treats 15% of the total patients in Japan, to determine the reasons for having diagnostic tests in newly infected individuals. HIV-infected patients who visited our clinic for the first time between 2011 and 2014 were analyzed.ResultsThe 598 study patients comprised one-third of the total reported number of new patients in Tokyo during the study period. 76% were Japanese MSM. The reasons for being tested which led to the diagnosis was voluntary testing in 32%, existing diseases in 53% (AIDS-defining diseases in 22%, sexually transmitted infections (STI) in 8%, diseases other than AIDS or STIs in 23%) and routine pre-surgery or on admission screening in 15%. 52% and 74% of the study patients and patients presented with AIDS, respectively, had never been tested. The median CD4 count in patients with history of previous testing (315/μL) was significantly higher than that of patients who had never been tested (203/μL, p<0.001).ConclusionsOnly 32% of the newly HIV diagnosed patients were diagnosed because of voluntary testing, and 53% were diagnosed due to presence of other diseases. These results remain unchanged from our previous report 10 years earlier (2000–2004) on newly diagnosed patients at the same clinic. HIV testing has not been widely used by newly diagnosed patients in the Tokyo metropolitan area.

Molecular interplay between T-Antigen and splicing factor, arginine/serine-rich 1 (SRSF1) controls JC virus gene expression in glial cells.

BackgroundHuman polyomavirus JCV is the etiologic agent of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease characterized by lytic infection of glial cells in the central nervous system. PML is seen primarily in immunosuppressed patients and is mainly classified as an AIDS-defining disease. In addition to structural capsid proteins, JCV encodes multiple regulatory proteins, including T-antigen and agnoprotein, which are required for functional lytic infection. Previous studies have suggested that molecular interaction between viral proteins and host factors play an important role in reactivation of JCV and progression of the viral life cycle in glial cells. Recently, serine/arginine rich splicing factor 1 (SRSF1), a cellular alternative splicing factor, was identified as a strong negative regulator of JCV in glial cells. SRSF1 inhibits JCV gene expression and viral replication by directly interacting with viral promoter sequences. Here, we have investigated possible impact of JCV regulatory proteins, T-antigen and agnoprotein, on SRSF1-mediated suppression of JCV gene expression in glial cells.ResultsReporter gene analysis has suggested that T-antigen rescues viral transcriptional suppression mediated by SRSF1. Further analyses have revealed that T-antigen promotes viral gene expression by suppressing SRSF1 gene transcription in glial cells. A subsequent ChIP analysis revealed that T-antigen associates with the promoter region of SRSF1 to induce the transcriptional suppression.ConclusionsThese findings have revealed a molecular interplay between cellular SRSF1 and viral T-antigen in controlling JCV gene expression, and may suggest a novel mechanism of JCV reactivation in patients who are at risk of developing PML.

Expression of Signaling Molecules in Progressive Multifocal Leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a debilitating demyelinating disease of the CNS caused by the infection and destruction of glial cells by JC virus (JCV) and is an AIDS-defining disease. Infection with JCV is common and most people acquire antibodies early in life. After initial infection, JCV remains in an asymptomatic persistent state and can be detected by PCR in many tissues including brain. A major question in PML pathogenesis is how the virus reactivates from persistence in HIV-1/AIDS. Our studies with primary cultures of glial cells have implicated transcription factors NF-κB and NFAT4, which bind to a unique site in the JCV noncoding control region and stimulate viral gene expression. Furthermore, these transcription factors are controlled by pathways downstream of proinflammatory cytokines, e.g., TNF-α activates NF-κB and stimulates JCV transcription. We hypothesize that HIV-1/PML initiation may involve reactivation of JCV by cytokine disturbances in the brain such as occur in HIV-1/AIDS. In this study, the objective was to evaluate HIV-1/PML clinical samples for expression of TNF-α and its receptors and subcellular localization of NF-κB p65 and NFAT4 compared to non-PML controls. We evaluated HIV-1/PML clinical samples and non-PML controls for expression of TNF-α and its receptors and subcellular localization of NF-κB p65 and NFAT4 using Western blot and immunohistochemistry. Consistent with our hypothesis, compared to non-PML controls, HIV-1/PML tissue has high levels of TNF-α and TNFR1 expression and NF-κB and NFAT4 were preferentially localized to the nucleus. The involvement of TNF-α/NF-κB/NFAT4 signaling in JCV regulation that we reported from experiments in cultured human glial cells may be clinically relevant in PML.

Suicidal ideation and suicide attempts among human immunodeficiency virus-infected adults: differences in risk factors and their implications

ABSTRACTMany studies have investigated risk factors for suicidal ideation and suicide attempt; however, most have failed to show differences in risk factors between suicidal ideation and suicide attempt among the human immunodeficiency virus (HIV)-infected population. This study was designed to identify differences in risk factors between suicidal ideation and suicide attempts among HIV-infected adults in Seoul. A face-to-face survey of 457 HIV-infected adults was conducted by the Seoul Metropolitan Government in 2013. Multivariate logistic regression analysis was used to identify factors associated with suicidal ideation and suicide attempt. Among 422 participants, 44% had suicidal ideation, and 11% had suicide attempts. The independent risk factors for suicidal ideation were young and middle age, living with someone, history of AIDS-defining opportunistic disease, history of treatment for depression, lower social support, and psychological status. Beneficiaries of National Medical Aid, economic barriers to treatment, history of treatment for depression, and lower psychological status were independently associated with suicide attempts. Patients with HIV in Korea were treated without cost in some centers. Thus, experiencing an economic barrier to treatment might be due in part to ignorance of HIV care policies. Our findings indicate that suicide attempts are associated with socioeconomic factors and information inequality regarding medical care. In conclusion, suicidal ideation closely associated with the psychosocial factors, whereas suicide attempt demonstrates a stronger association with socioeconomic factors. Suicide prevention measures should be implemented to provide information to help HIV-infected patients.

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BackgroundIn sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)–associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast.MethodsWe included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non–AIDS-defining cancer, non–AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies.ResultsA total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies.ConclusionsIn this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Factors associated with death during tuberculosis treatment of patients co-infected with HIV at the Yaoundé Central Hospital, Cameroon: an 8-year hospital-based retrospective cohort study (2006-2013).

BackgroundContributors to fatal outcomes in TB/HIV co-infected patients actively undergoing TB treatment are poorly characterized. The aim was to assess factors associated with death in TB/HIV co-infected patients during the initial 6 months of TB treatment.MethodsWe conducted a hospital-based retrospective cohort study from January 2006 to December 2013 at the Yaoundé Central Hospital, Cameroon. We reviewed medical records to identify hospitalized co-infected TB/HIV patients aged 15 years and older. Death was defined as any death occurring during TB treatment, as per the World Health Organization's recommendations. We conducted logistic regression analysis to identify factors associated with a fatal outcome. Magnitudes of associations were expressed by adjusted odds ratio (aOR) with 95% confidence interval.ResultsThe 337 patients enrolled had a mean age of 39.3 (standard deviation 10.3) years and 54.3% were female. TB treatment outcomes were distributed as follows: 205 (60.8%) treatment success, 99 (29.4%) deaths, 18 (5.3%) not evaluated, 14 (4.2%) lost to follow-up, and 1 (0.3%) failed. After exclusion of patients lost to follow-up and not evaluated, death in TB/HIV co-infected patients during TB treatment was associated with a TB diagnosis made before 2010 (aOR = 2.50 [1.31–4.78]; p = 0.006), the presence of other AIDS-defining diseases (aOR = 2.73 [1.27–5.86]; p = 0.010), non-AIDS comorbidities (aOR = 3.35 [1.37–8.21]; p = 0.008), not receiving cotrimoxazole prophylaxis (aOR = 3.61 [1.71–7.63]; p = 0.001), not receiving antiretroviral therapy (aOR = 2.45 [1.18–5.08]; p = 0.016), and CD4 cells count <50 cells/mm3 (aOR = 16.43 [1.05–258.04]; p = 0.047).ConclusionsThe TB treatment success rate among TB/HIV co-infected patients in our setting is low. Mortality was high among TB/HIV co-infected patients during TB treatment and is strongly associated with clinical and biological factors, highlighting the urgent need for specific interventions focused on enhancing patient outcomes.

Characteristics of late presentation of HIV infection in MSM and heterosexual adults in Portugal 2011-2013.

IntroductionIt is estimated that over half of newly diagnosed HIV infections in Europe present late. An HIV positive individual presenting late to care represents a missed opportunity to benefit from treatment, increasing the risk of morbidity and mortality at an individual level, and onward disease transmission at population level. Reducing late presentation is a strategic priority of the Portuguese HIV/AIDS program. We set out to describe the characteristics of late presentation in the two largest transmission risk groups currently in Portugal to inform HIV prevention and treatment.MethodsWe extracted details of all notified cases from individuals over 15 years with a laboratory confirmed HIV diagnosis made between January 2011 and December 2013 from the Portuguese HIV surveillance database and selected cases from heterosexuals and men who have sex with men (MSM). We defined late presentation as an initial CD4 count <350 cells/mm3 or presence of AIDS-defining disease at time of HIV diagnosis. We calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) for characteristics associated with late presentation in separate logistic regression for heterosexuals and MSM.ResultsOf 4219 HIV positive cases notified, 2589 (61%) were heterosexuals and 1220 (29%) were MSM. A total of 1586 (38%) cases presented late of which 1037 (40%) were heterosexual and 328 (27%) were MSM. The median age at late presentation was 40 in heterosexual women, 46 in heterosexual men and 35 in MSM. A total of 1446 (55%) of heterosexual HIV positive adults were unaware of having had a high risk sexual contact. Late presentation among heterosexuals was associated with being male (aOR=1.58 95% CI 1.29–1.93), not knowing a partners’ HIV status (OR=1.59 95% CI 1.35–1.87) and age, increasing the odds of late presentation by a factor of 1.02 per year (95% CI 1.01–1.03). Among MSM, only age was associated with late presentation, increasing by 1.04 (95% CI 1.03–1.05) per year.ConclusionsPortuguese HIV prevention programs need to increase the risk awareness of heterosexuals, particularly men, to reduce missed opportunities for early diagnosis. As half of all cases presenting late are aged 40 and over, we recommend that general HIV outreach services and specialist services for MSM review their accessibility and acceptability to both middle and older-aged clients.

Gender Differences in Risk Factors for Delayed Diagnosis of HIV/AIDS in a Midsized City of Brazil.

Patients treated in the specialized service at a midsized city in Brazil participated in a cross-sectional study that aimed to identify the risk factors for delayed diagnosis of HIV/AIDS. Through interviews and review of medical records, information was collected on sociodemographic and clinical characteristics and diagnoses. The study included 403 patients, of whom 216 (53.6%) were male and 311 (77.1%) had ≤8 years of education. According to the criteria adopted in this study, 162 (40.2%) of the participants had a late diagnosis of AIDS. Only 19 (4.7%) were diagnosed by routine examinations and 45 (11.2%) presented with AIDS-defining disease at the time of diagnosis. After adjustments, the results showed that having more education was protective against a late diagnosis for women. With the advance of the AIDS epidemic to small town and rural Brazil, vulnerable populations now include low-income and less educated women, most of whom have had monogamous relationships throughout their lives.

The continued ageing of people with AIDS in Italy: recent trend from the national AIDS Registry.

Introduction. In industrialized countries, the availability of highly active antiretroviral therapy (HAART) caused a slow but substantial ageing of the AIDS epidemic mainly due to the longer survival of persons with HIV/AIDS which has turned HIV into a manageable, chronic disease. The number of older people with AIDS is growing in many European countries. We described the impact of AIDS among persons aged 50 years or more in Italy and compared the characteristics of these cases with those of persons diagnosed with AIDS at an age younger than 50. Methods. The source of data was the Italian AIDS Registry, from 1982 to 2011. We defined "older" persons those aged 50 years or more, and younger individuals those aged less than 50 years. We built two multivariate logistic regression models: the first one to identify factors associated with being older, and the second one to identify AIDS-defining diseases correlated with being older. Variables with a P value of <0.05 were entered in the model. Results. Of the total AIDS cases, 10.5% were among persons older than 49 years. This proportion progressively increased from 0.0% in 1983 to 26.4% in 2011. Among older cases, the incidence of AIDS was 2.0 per 100 000 residents in 1996, then decreased to 1.4 per 100 000 in 2000 and levelled off around 1 per 100 000 residents until 2011. Compared to younger cases, older cases were more frequently males, Italians, diagnosed with AIDS in recent years, residing in Northern or Central Italy, non-injecting drug users, and late testers. Discussion. These findings stress the need for physicians to consider carefully the possibility of HIV infection among older individuals not to miss the opportunity to deliver prevention messages, offer HIV testing, and make an early diagnosis.

A Man With Newly Diagnosed HIV/AIDS With Unusual Severe Opportunistic Infection and No AIDS-Defining Disease

A Man With Newly Diagnosed HIV/AIDS With Unusual Severe Opportunistic Infection and No AIDS-Defining Disease

Outcomes among HIV-1 Infected Individuals First Starting Antiretroviral Therapy with Concurrent Active TB or Other AIDS-Defining Disease

BackgroundTuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the “Prospective Evaluation of Antiretrovirals in Resource-Limited Settings” (PEARLS) study.MethodsParticipants were categorized retrospectively into three groups according to presence of active confirmed or presumptive disease at ART initiation: those with pulmonary and/or extrapulmonary TB (“TB” group), those with other non-TB AIDS-defining disease (“other disease”), or those without concurrent TB or other AIDS-defining disease (“no disease”). Primary outcome was time to the first of virologic failure, HIV disease progression or death. Since the groups differed in characteristics, proportional hazard models were used to compare the hazard of the primary outcome among study groups, adjusting for age, sex, country, screening CD4 count, baseline viral load and ART regimen.Results31 of 102 participants (30%) in the “TB” group, 11 of 56 (20%) in the “other disease” group, and 287 of 1413 (20%) in the “no disease” group experienced a primary outcome event (p = 0.042). This difference reflected higher mortality in the TB group: 15 (15%), 0 (0%) and 41 (3%) participants died, respectively (p<0.001). The adjusted hazard ratio comparing the “TB” and “no disease” groups was 1.39 (95% confidence interval: 0.93–2.10; p = 0.11) for the primary outcome and 3.41 (1.72–6.75; p<0.001) for death.ConclusionsActive TB at ART initiation was associated with increased risk of mortality in HIV-1 infected patients.

What is the correct therapeutic approach in patients with advanced HIV infection associated with ≥ 3 AIDS defining illness?

Case report We present a case of a 29 years old patient, MSM, confirmed with HIV infection in 2007 but who do not accept the diagnosis and returns to our service in 2013. He was diagnosed with generalized Kaposi sarcoma (extensive skin lesions, sores in the mouth and cavum, lung injury; the clinical diagnosis was confirmed by skin biopsy and lung CT), cerebral toxoplasmosis (specific to brain MRI image with anti-toxoplasma IgG positive), disseminated tuberculosis (positive blood cultures for M tuberculosis) and genital herpes with large lesions and necrotic component, at a CD4 = 2 cells/cmm. Treatment was complex, for getting every opportunistic infection; because of the complexity of the case and the hematologic associated events (severe leucopenia, anemia and thrombocytopenia) has not been discussed the specific therapy for Kaposi’ sarcoma. After 6 weeks of antinfectious treatment and correction of associated metabolic and hematological disorders, the antiretroviral therapy with Abacavir, Epivir and Raltegravir was introduced. Without developing immune reconstitution syndrome the evolution was unfavorable to death. Conclusion We discuss the correct therapeutic approach for the treatment of AIDS-defining diseases associated and the proper management of this type of patient.

Welfare Homes for Patients Living with HIV/AIDS in Andalusia

To study the AIDS welfare homes (AWHs) in Andalusia, assess their resources and the services provided, and describe the characteristics of their residents. Cross-sectional, observational study; an interview questionnaire technique was used with the managers and the residents of the AWHs. A total of 7 AWHs and 96 residents were included; 32% of the staff were health care workers and 45.5% volunteers. The occupancy rate was 86% (2007) and 96% (2008). Residents' characteristics: mean age 45.6 years, 73% male, 92% with at least 1 AIDS-defining disease, median Karnofsky index 60 (50-80), and median Barthel index 80 (40-100). Half the residents had physical sequelae and 31% mental sequelae. The AWHs perform an important role in the care of certain types of patients with HIV infection. They require human and material resources to be able to tackle the immense difficulties associated with this group of patients.