Highly Active Antiretroviral Therapy Era Research Articles

Tuberculosis in HIV-infected persons in British Columbia during the HAART era.

Prior to the introduction of highly active antiretroviral therapy (HAART), active tuberculosis (TB) was a major contributor to HIV-related morbidity and mortality in Canada and other low-incidence regions. We performed this study to examine TB incidence, clinical manifestations and screening uptake in HIV-infected TB patients during the era of HAART therapy. We performed a retrospective study on all HIV-infected TB patients in British Columbia over a 10-year period (2003-2012). Demographic and clinical characteristics were extracted along with screening and treatment outcomes. Trends in provincial TB incidence, HIV testing and HAART prevalence were also examined. In total, 2,839 TB cases were identified in BC during this period, including 129 HIV-infected TB patients. Surprisingly, only 64 HIV-infected TB patients (50%) had a documented screening tuberculin skin test (TST) prior to TB diagnosis. Of the 39 HIV-infected TB patients with prior TST positivity, 38 (97.4%) had not completed a course of isoniazid preventive therapy. TB incidence decreased significantly in the HIV-infected population of BC over the study period, from 1.9 to 0.5 TB cases per 1,000 HIV-infected individuals (p<0.001). The incidence of HIV-TB decreased significantly over the past decade despite suboptimal latent TB infection screening and prevention practices. This decrease in TB incidence is likely attributable to the increased uptake of HAART. Consideration should be given to intensifying prevention efforts to accelerate TB elimination in HIV-infected populations in low-incidence regions.

Heart failure in patients with human immunodeficiency virus infection: epidemiology, pathophysiology, treatment, and future research.

With the advent of highly active antiretroviral therapy (HAART), human immunodeficiency virus type 1 (HIV-1) infection has become a chronic disease with longer life expectancy.1 The HIV Outpatient Study showed that, with the addition of antiretroviral therapy (ART), mortality declined from 29.4 to 8.8 per 100 person-years.2 More recent data indicate that the proportions of patients expected to survive 5, 10, and 15 years after seroconversion in the HAART era are 99%, 93%, and 89%, respectively.3 With the increased life expectancy and decreased morbidity from opportunistic infections, the recognition and importance of chronic complications associated with HIV-1 infection are becoming more evident. Cardiac diseases are common complications found in these patients. The spectrum of heart diseases varies significantly between developed and developing countries and, in developed countries, between pre-HAART and post-HAART eras.4 Among them, HIV-associated cardiomyopathy, broadly defined as a decreased left ventricular (LV) ejection fraction or dilated LV by imaging studies, with or without symptoms of heart failure, is currently recognized as a major long-term complication of HIV-1 infection in developing countries; however, it is still prevalent in developed countries.4 Many questions regarding its pathogenesis and treatment remain unanswered. The epidemiology of HIV-associated cardiomyopathy has changed since the first report in 1986.5 The advent of HAART has significantly altered both the incidence and prevalence of this disease, and the definition of HIV-associated cardiomyopathy has also evolved from one of primarily systolic dysfunction to now reflect the growing recognition of diastolic dysfunction in these patients. The incidence of HIV-associated cardiomyopathy is difficult to ascertain because very few studies actually evaluated this measure. In the pre-ART era, HIV-associated cardiomyopathy was defined as symptomatic, systolic dysfunction with a dilated LV and was seen almost exclusively in patients with advanced HIV disease and AIDS. These older studies, …

Modelling clinical progression and health care utilization of HIV‐positive patients in British Columbia prior to death

The extent to which clinical progression of HIV-positive patients leads to an increase in health care utilization, especially prior to their death, is unknown. Thus, we modelled trends in CD4 cell count and emergency department utilization and the likelihood of an emergency department visit leading to a transfer to an acute care-level facility prior to a patient's death from nonaccidental causes. Eligible patients initiated highly active antiretroviral therapy (HAART) in British Columbia between August 1996 and June 2006 (n = 457). Patients were followed until their death, which occurred on or before 30 June 2007 (period in which the emergency department visit data were available). Trends were modelled using generalized mixed effects. Patients experienced a significantly steep decline in CD4 cell count and a corresponding increase in the number of emergency department visits and transfers to acute-level facilities in the 5 years prior to death. For every 6-month interval prior to death, the CD4 cell count decreased by 13.22 cells/μL, the risk of experiencing an emergency department visit increased by 9%, and among those ever admitted, the odds ratio of being transferred to an acute care-level facility increased by 3%. We showed that patients experienced a steep decline in CD4 cell count, which was associated with an increase in health care utilization prior to their death. These findings highlight the substantial residual avoidable burden that unsuccessfully managed HIV disease poses, even in the HAART era. Further strategies to enhance sustained and successful engagement in care are urgently needed to mitigate high health care utilization.

Anal Squamous Cell Cancer in African Americans With and Without HIV: A Comparative Study

1.1 Background: The incidence of anal carcinoma has increased over the last few decades especially in African Americans (AA) despite the use of highly active anti-retroviral therapy (HAART). Here, we retrospectively review oncologic outcomes of AA patients with anal squamous cell carcinoma (SCC) with and without HIV to further examine the cause of this trend. Materials and Methods: All adult AA patients diagnosed with anal SCC from 2000 to 2007 who met inclusion were examined. All patients were staged according to the American Joint Committee on Carcinoma (AJCC) sixth edition staging classification. Patients were divided into two cohorts: HIV (-) and HIV (+). Demographics, comorbidities, and oncologic outcomes were analyzed. Results: Twenty-two AA patients with anal SCC were analyzed. Fifteen (68.%) were HIV (+) and seven (32%) were negative. Seventy-four percent of HIV (+) patients were on HAART therapy at the time of diagnosis. The HIV (+) cohort was significantly younger, mostly male, and had more comorbidities compared to the negative cohort. There was no difference in tumor, nodal or metastasis (TNM) stage for both cohorts. HIV (+) patients were more likely to receive non-operative therapy. The 5-year survival rate for HIV negative and positive patients was 57% and 58%, respectively. AJCC stage was the only factor predictive of survival after performing Cox hazard proportional regression analysis, HR: 1.96 (95% CI, 0.987 to 3.881). Conclusions: In the HAART era, HIV (+) AA patients are at high risk of developing anal SCC. However, the prognosis of HIV (+) AA with anal SSC is similar to that of their HIV (-) counterparts. Carcinoma stage is the only factor predictive of survival.

Immune recovery uveitis: pathogenesis, clinical symptoms, and treatment.

IRU is the most common form of immune reconstitution inflammatory syndrome in HIV-infected patients with cytomegalovirus retinitis who are receiving highly active antiretroviral therapy (HAART). Among patients with CMV in the HAART era, immune recovery may be associated with a greater number of inflammatory complications, including macular edema and epiretinal membrane formation. Given the range of ocular manifestations of HIV, routine ocular examinations and screening for visual loss are recommended in patients with CD4 counts <50 cells/μL. With the increasing longevity of these patients due to the use of HAART, treatment of IRU may become an issue in the future. The aim of this paper is to review the current literature concerning immune recovery uveitis. The definition, epidemiology, pathophysiology, clinical findings, complications, diagnosis, and treatment are presented.

Increases in Duration of First Highly Active Antiretroviral Therapy Over Time (1996–2009) and Associated Factors in the Multicenter AIDS Cohort Study

Antiretroviral therapy (ART) regimens changes occur frequently among HIV-infected persons. Duration and type of initial highly active antiretroviral therapy (HAART) and factors associated with regimen switching were evaluated in the Multicenter AIDS Cohort Study. Participants were classified according to the calendar period of HAART initiation: T1 (1996-2001), T2 (2002-2005), and T3 (2006-2009). Kaplan-Meier curves depicted time from HAART initiation to first regimen changes within 5.5 years. Cox proportional hazards regression models were used to examine factors associated with time to switching. Of 1009 participants, 796 changed regimen within 5.5 years after HAART initiation. The percentage of participants who switched declined from 85% during T1 to 49% in T3. The likelihood of switching in T3 decreased by 50% (P < 0.01) compared with T1 after adjustment for pre-HAART ART use, age, race, and CD4 count. Incomplete HIV suppression decreased over time (P < 0.01) but predicted switching across all time periods. Lower HAART adherence (≤95% of prescribed doses) was predictive of switching only in T1. In T2, central nervous system symptoms predicted switching [relative hazard (RH) = 1.7; P = 0.012]. Older age at HAART initiation was associated with increased switching in T1 (RH = 1.03 per year increase) and decreased switching in T2 (RH = 0.97 per year increase). During the first 15 years of the HAART era, initial HAART regimen duration lengthened and regimen discontinuation rates diminished. Both HIV RNA nonsuppression and poor adherence predicted switching before 2001 while side effects that were possibly ART related were more prominent during T2.

Small Bowel Kaposiʼs Sarcoma: An Unusual Cause of GI Bleeding

Purpose: A 34-year-old previously healthy man presented with 1 week of melena and new right sided hemiplegia for 1 month. Initial hemoglobin was 6 g/dL from a baseline of 13.5 g/dL two years prior. Brain MRI showed two ring enhancing lesions in the left cortex and cerebellum suspicious for toxoplasmosis. An HIV antibody test was positive, with a CD4 count of 1. An upper endoscopy was performed and showed white adherent material in the esophagus (biopsy pathology positive for candidiasis), gastric erythema and normal duodenum without a bleeding source. Colonoscopy showed normal terminal ileal and colonic mucosa. A capsule endoscopy demonstrated a raised medium-sized submucosal erythematous mass in the mid-jejunum, suspicious for Kaposi's sarcoma (KS). A detailed skin exam yielded a violaceous plaque on the abdomen, with biopsy pathology diagnostic of KS. The patient was started on antiretroviral therapy (ART) and treatment for cerebral toxoplasmosis, with no further episodes of melena. KS is a vascular tumor that is associated with human herpesvirus 8 and is the most common tumor arising in HIV-infected persons. Its prevalence is increased with lower CD4 counts. KS was over 20,000 times more common in persons with AIDS than in the general population prior to the widespread use of highly active antiretroviral therapy (HAART), and the incidence has declined substantially since that time. Although KS can involve virtually any site in the body, cutaneous disease is most common and is the usual initial presentation for KS. The most frequent sites of noncutaneous disease are the oral cavity, gastrointestinal tract (most commonly the small intestine) and respiratory system. Prior to widespread ART, the gastrointestinal tract was involved in approximately 40% of patients with KS at initial diagnosis, and in up to 80% at autopsy. However, visceral involvement as the initial manifestation of KS in the HAART era is relatively uncommon. GI lesions may be asymptomatic or cause weight loss, abdominal pain, nausea and vomiting, upper or lower gastrointestinal bleeding, malabsorption, intestinal obstruction or diarrhea. On endoscopy, KS lesions are easily recognized as hemorrhagic nodules that can appear anywhere along the GI tract. In the HAART era the incidence of AIDS-related KS has dramatically decreased to less than 10% of the incidence reported in the pre-HAART era, but it is still recognized as a primary AIDS-defining illness that can lead to significant morbidity. Rarely, visceral KS can present as occult or gross GI bleeding. In persons with underlying AIDS presenting with anemia and/or GI bleeding, it is important for physicians to consider intestinal KS as a possible etiology.

Autoimmune diseases-related arthritis in HIV-infected patients in the era of highly active antiretroviral therapy

Autoimmune diseases-related arthritis has been rarely reported in HIV-1-infected patients. We aimed to investigate the incidence and clinical manifestations of autoimmune diseases-related arthritis in HIV-infected patients in the era of highly active antiretroviral therapy (HAART) in Taiwan. We retrospectively reviewed medical records of all HIV-infected patients who had a diagnosis of autoimmune arthritis between 1993 and 2013. Demographic characteristics, clinical manifestations, serial CD4 and CD8 lymphocyte counts and plasma HIV viral loads, HLA-B27 status, and treatment response to HIV and rheumatic diseases were recorded. During the 20-year study period, totally 26 HIV-infected patients with autoimmune arthritis (0.7%) were diagnosed among 3623 HIV-infected patients. There were 18 patients with ankylosing spondylitis (AS), six with rheumatoid arthritis (RA), one with psoriatic arthritis, and one with Sjögren's syndrome. HLA-B27 antigens were all detected positive of AS patients. Fifteen patients (57.7%) developed autoimmune arthritis after HAART was initiated. The median age and CD4(+) T lymphocyte counts at the diagnosis of autoimmune arthritis were 35 (20-62 years) and 406 (3-695 cells/μL), respectively. Three patients had typical presentations of Reiter's syndrome. Both AS and RA patients achieved a good virological response with undetectable plasma HIV RNA load 12 months after receiving HAART(85.71% vs. 80%, respectively, p = 0.999). The treatment response to antirheumatic medications were similar between AS patients and RA patients (77.8% vs. 50%, p = 0.3068), but seems to be better than that reported for the general population (30-40%). A low prevalence of autoimmune arthritis among HIV-infected patients in the era of HAART was similar to that of the general Taiwanese population. Clinical manifestations of HIV-infected patients were similar to those described in HIV-uninfected patients. However, the treatment response to antirheumatic agents was better in HIV-infected patients in our study.

Temporal Trends, Clinical Characteristics, and Outcomes of Histoplasmosis in a Tertiary Care Center in Kentucky, 2000 to 2009

The impact of highly active antiretroviral therapy (HAART) on the epidemiology of AIDS-associated histoplasmosis in the past decade is poorly defined. Among 100 patients with histoplasmosis in an endemic region between 2000 and 2009, 42 patients were immunocompetent, 32 were infected with HIV, and 26 were non-HIV-immunocompromised patients. The percentage with HIV decreased 67% in 2000-2001 to 18% in 2008-2009 (P = .004), while the proportion of non-HIV immunocompromised patients increased, 8% to 41% (P = .14). Histoplasma antigen was the most sensitive test (73%), whereas potassium hydroxide examination of clinical specimens was the least sensitive test (33%) in all 3 groups. Bronchoalveloar fluid culture (74%) had the highest yield among the cultures. The relapse rate was higher in HIV-infected patients compared to the other 2 groups (P = .04). The epidemiology of histoplasmosis in our endemic area has changed during the era of HAART. Organ transplantation and increasing use of immunosuppressive agents for chronic inflammatory conditions in non-HIV patients now account for most of the cases of histoplasmosis.

HIV-Associated Lipodystrophy: Impact of Antiretroviral Therapy

In the late 1990s, reports of unusual changes in body fat distribution named 'lipodystrophy' (LD) began to appear in HIV patients mitigating the enormous enthusiasm about improvement of survival and quality of life provided by the combinations of antiretroviral (ARV) drug classes, the so-called highly active antiretroviral therapy (HAART), which had just become available at that time. The objective of this paper is to critically review the literature on LD and to discuss the impact of newer ARV agents, namely atazanavir, darunavir and raltegravir, as well as strategies of the late HAART era, including single-tablet regimens and nucleoside-sparing regimens. Studies in which LD was measured by dual-energy x-ray absorptiometry or by abdominal computed tomography or magnetic resonance imaging scan only, were included. We were unable to identify studies depicting a negative impact of drugs or ARV regimens on limb fat loss. On the contrary, a few studies identified a negative impact of atazanavir/ritonavir or darunavir/ritonavir on trunk fat increase. It should be noted that this anthropometric measure is a poor instrument since it cannot distinguish between subcutaneous and visceral fat. We conclude that presumably the body fat changes currently observed in HIV-infected patients is the net result of competing phenomena: on one side the natural history of lipohypertrophy as a result of HIV and HAART impact, and on the other side the physiological body fat changes observed in the aging population.

Incidence and risk of lung cancer in HIV-infected patients

Lung cancer is one of the most common non-AIDS-defining malignancies among HIV-infected patients. The incidence of lung cancer has significantly increased in the HIV-positive population in recent years. The purpose of this study was to summarize the incidence and risk of lung cancer in published population-based studies of people with HIV/AIDS. Published literature from PubMed, Embase, the Web of Science, and Google Scholar was retrieved. Sixty-five publications were selected and assessed for the following parameters: research coverage and location; continent; study period; duration of follow-up; lung cancer cases; HIV cases; incidence rate; and overall SIR or adjusted IRR. In addition, the risk of lung cancer was compared based on age, gender, HIV exposure category, CD4 count, and periods with highly active antiretroviral therapy (HAART). Lung cancer risk was greater among HIV-infected individuals compared with the general population. SIRs or adjusted IRRs were 1.5-3.4 in Europe, 0.7-6.9 in the USA, and 5.0 in Africa. Most, but not all studies did not observe a significant change in the incidence and risk of lung cancer between the pre-HAART and HAART eras. In most studies, the risk of lung cancer was higher among women, younger individuals, and injection drug users (IDUs), but the incidence of lung cancer was higher among men and the elderly. No significant trend in lung cancer risk across CD4 cell count categories was reported among the selected articles. Our study suggests an increase in the incidence and risk of lung cancer in HIV/AIDS population is worldwide. The effect of HAART on the incidence and risk of lung cancer is in dispute. The risk of lung cancer based on gender differences, especially among females, as well as IDUs, requires further investigation.

Prevalence of Ocular Manifestations of HIV/AIDS in the Highly Active Antiretroviral Therapy (HAART) Era: A Different Spectrum in Central South China

Purpose: To investigate ocular manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in a population in central south China during a time of highly active antiretroviral therapy (HAART).Methods: A cross-sectional study in central south China was performed between June 2009 and April 2010. Ocular examinations were performed on recruited patients with HIV/AIDS. Systemic information (including CD4+ T cell count) was also collected where possible.Results: Among 1041 patients (2082 eyes) with HIV/AIDS enrolled in our study, we found a broad spectrum of ocular manifestations related to HIV/AIDS. The prevalence of HIV-associated ocular disease was 23.73% (247 patients). Of those with ocular complications, 87.85% had CD4 counts <200 cells/µL. HIV retinopathy (12.68%) was the most common HIV-associated ocular finding, followed by cytomegalovirus retinitis (6.72%). Prevalences of visual impairment and blindness were 7.59% and 0.77%, respectively.Conclusions: This epidemiologic study shows the spectrum of ocular lesions associated with HIV/AIDS in central south China. Our findings highlight the need for routine ophthalmic examinations in this population, even in patients who are asymptomatic, especially those at high risk, in the era of HAART.

Abstract 1240: A flexible antibody-based strategy targeting CD71 for the treatment of AIDS-related non-Hodgkin's lymphoma.

Abstract AIDS related non-Hodgkin's lymphoma (AIDS-NHL) remains a significant clinical problem in the era of effective multiple-agent highly active anti-retroviral therapy (HAART). While an overall decrease in the incidence of AIDS-NHL has been seen in the HAART era, the risk for AIDS-NHL remains elevated, and not all AIDS-NHL subtypes have decreased in incidence, with the incidence of Burkitt's lymphoma (BL) remaining unchanged. In fact, AIDS-NHL is now the most common AIDS-related cancer in developed countries, where NHL accounts for 23-30% of all AIDS-related deaths. We have previously developed an antibody-avidin fusion protein (ch128.1Av) specific for the human transferrin receptor 1 (TfR1/CD71), a receptor that is overexpressed on cancer cells due to their high demand for iron. This fusion protein exhibits an increased in vitro cytotoxicity against malignant hematopoietic cells compared to the parental antibody without avidin (ch128.1). This cytotoxicity is due to the ability of ch128.1Av to decrease cell surface TfR1, triggering its intracellular sequestration and degradation, with the subsequent induction of lethal iron deprivation. However, both ch128.1Av and ch128.1 confer protection in murine models of human disseminated multiple myeloma. ch128.1Av is also a universal delivery system and its cytotoxicity can be further enhanced by its conjugation with biotinylated drugs making it a unique molecule capable of a two-pronged attack against malignant cells through drug delivery and direct cytotoxic activity through iron starvation. The main goal of this study is to evaluate the potential use of ch128.1Av alone and as a delivery vehicle as a possible AIDS-NHL therapy. We found that, when used alone, ch128.1Av exhibits significant cytotoxic activity against two representative AIDS-NHL cell lines: 2F7 (AIDS-Burkitt's NHL) and RRBL (AIDS-diffuse large B-cell lymphoma). Importantly, the level of cytotoxicity was similar to that observed using the highly sensitive human B lymphoblastoid cell line IM-9. In addition, the cytotoxicity dramatically increases when this fusion protein is conjugated to biotinylated saporin 6 (b-SO6), a plant ribosome inactivating protein that blocks protein synthesis, resulting in an immunotoxin. We also found that non-activated (resting) B cells isolated from the peripheral blood of healthy individuals are resistant to ch128.1Av, but sensitive to ch128.1Av complexed to b-SO6, which can be explained by the different mechanisms of action of the fusion protein alone (iron starvation) and that of the immunotoxin (protein synthesis inhibition). We have previously reported ch128.1Av alone, or complexed to b-SO6, are not toxic to normal human hematopoietic stem cells, which can be explained by the lack of TfR1 expression on such cells. Our results suggest the potential use of anti-TfR1 antibody-mediated approaches as therapeutic interventions against AIDS-NHL. Citation Format: Tracy R. Daniels-Wells, Lai Sum Leoh, Daniel Widney, Dharma R. Thapa, Jose Leon Merino, Larry Magpantay, Otoniel Martínez-Maza, Manuel L. Penichet. A flexible antibody-based strategy targeting CD71 for the treatment of AIDS-related non-Hodgkin's lymphoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1240. doi:10.1158/1538-7445.AM2013-1240

Renal Transplantation in HIV-infected Patients: Experience at a Tertiary Hospital in Spain and Review of the Literature

BackgroundThe use of highly active antiretroviral therapy (HAART) has decreased the morbidity and mortality in HIV-infected patients. The kidney transplantation (KT) survival rate is similar to that of HIV-negative transplant recipients. The consensus criteria for the selection of HIV patients for transplantation include: no opportunistic infections, CD4 lymphocyte count greater than 200 cells/μL, and an undetectable viral load. In Spain, HIV-infected patients present with different characteristics compared to American recipients; this could influence posttransplantation outcomes. ObjectiveThis study analyzed the outcome and the clinical characteristics of HIV-infected patients who received KT in Spain in the HAART era. MethodsWe retrospectively reviewed the clinical charts of seven adult HIV-infected recipients of primary renal allografts between January 2001 and June 2012. Patient inclusion criteria met the American and Spanish guidelines. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil, and steroids. ResultsThe median age was 44.8 years (interquartile amplitude = 9.4). The predominant mode of transmission was intravenous drug use (71.4%) and hepatitis C virus coinfection (71.4%). The most frequent cause of end-stage renal disease was glomerulonephritis (57.1%). Six patients (85.7%) were on HAART. All patients had controlled HIV infections with undetectable viral load and a median CD4 lymphocyte count of 504 cells/μL (IQA 599). Patients were followed for a median of 16.0 months (range, 3.0 to 96.6 months). Delayed graft function and acute rejection rates were 60% and 40%, respectively. The median creatinine level at the last follow-up was 1.58 mg/dL (IQA 1.15). In one case, a high-grade Epstein-Barr virus–related B cell lymphoma was diagnosed at 83 months after renal transplantation. ConclusionsKidney transplantation in HIV-infected patients is a safe, effective treatment for selected patients. Midterm graft survival was comparable to that of HIV-negative patients.

The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts

ObjectiveTo review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART).DesignTwo large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women’s Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively.MethodsAdjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era.ResultsCompared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2–2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3–1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8–2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02–8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3–1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5–2.4; p<0.001).ConclusionHIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality.

Rate of candidiasis among HIV-infected children in Spain in the era of highly active antiretroviral therapy (1997-2008).

BackgroundCandidiasis is the most common opportunistic infection seen in human immunodeficiency virus (HIV)-infected individuals. The aim of our study was to estimate the candidiasis rate and evaluate its trend in HIV-infected children in Spain during the era of highly active antiretroviral therapy (HAART) compared to HIV-uninfected children.MethodsWe carried out a retrospective study. Data were obtained from the records of the Minimum Basic Data Set from hospitals in Spain. All HIV-infected children were under 17 years of age, and a group of HIV-uninfected children with hospital admissions matching the study group by gender and age were randomly selected. The follow-up period (1997–2008) was divided into three calendar periods: a) From 1997 to 1999 for early-period HAART; b) from 2000 to 2002 for mid-period HAART; and c) from 2003 to 2008 for late-period HAART.ResultsAmong children with hospital admissions, HIV-infected children had much higher values than HIV-uninfected children during each of the three calendar periods for overall candidiasis rates (150.0 versus 6.1 events per 1,000 child hospital admissions/year (p < 0.001), 90.3 versus 3.1 (p < 0.001), and 79.3 versus 10.7 (p < 0.001), respectively) and for non-invasive Candida mycosis (ICM) rates (118.5 versus 3.8 (p < 0.001), 85.3 versus 2.3 (p < 0.001), and 80.6 versus 6.0 (p < 0.001), respectively). In addition, HIV-infected children also had higher values of ICM rates than HIV-uninfected children, except during the last calendar period when no significant difference was found (32.4 versus 1.2 (p < 0.001), 11.6 versus 0.4 (p < 0.001), and 4.6 versus 2.3 (p = 0.387), respectively). For all children living with HIV/AIDS, the overall candidiasis rate (events per 1,000 HIV-infected children/year) decreased from 1997–1999 to 2000–2002 (18.8 to 10.6; p < 0.001) and from 2000–2002 to 2003–2008 (10.6 to 5.7; p = 0.060). Within each category of candidiasis, both non-ICM and ICM rates experienced significant decreases from 1997–1999 to 2003–2008 (15.9 to 5.7 (p < 0.001) and 4.1 to 0.3 (p < 0.001), respectively).ConclusionsAlthough the candidiasis rate still remains higher than in the general population (from 1997 to 2008), candidiasis diagnoses have decreased among HIV-infected children throughout the HAART era, and it has ceased to be a major health problem among children with HIV infection.

Metropolitan Social Environments and Pre-HAART/HAART Era Changes in Mortality Rates (per 10,000 Adult Residents) among Injection Drug Users Living with AIDS

BackgroundAmong the largest US metropolitan areas, trends in mortality rates for injection drug users (IDUs) with AIDS vary substantially. Ecosocial, risk environment and dialectical theories suggest many metropolitan areas characteristics that might drive this variation. We assess metropolitan area characteristics associated with decline in mortality rates among IDUs living with AIDS (per 10,000 adult MSA residents) after highly active antiretroviral therapy (HAART) was developed.MethodsThis is an ecological cohort study of 86 large US metropolitan areas from 1993–2006. The proportional rate of decline in mortality among IDUs diagnosed with AIDS (as a proportion of adult residents) from 1993–1995 to 2004–2006 was the outcome of interest. This rate of decline was modeled as a function of MSA-level variables suggested by ecosocial, risk environment and dialectical theories. In multiple regression analyses, we used 1993–1995 mortality rates to (partially) control for pre-HAART epidemic history and study how other independent variables affected the outcomes.ResultsIn multivariable models, pre-HAART to HAART era increases in ‘hard drug’ arrest rates and higher pre-HAART income inequality were associated with lower relative declines in mortality rates. Pre-HAART per capita health expenditure and drug abuse treatment rates, and pre- to HAART-era increases in HIV counseling and testing rates, were weakly associated with greater decline in AIDS mortality.ConclusionsMortality among IDUs living with AIDS might be decreased by reducing metropolitan income inequality, increasing public health expenditures, and perhaps increasing drug abuse treatment and HIV testing services. Given prior evidence that drug-related arrest rates are associated with higher HIV prevalence rates among IDUs and do not seem to decrease IDU population prevalence, changes in laws and policing practices to reduce such arrests while still protecting public order should be considered.

Comparison of Treatment Regimens for Cytomegalovirus Retinitis in Patients with AIDS in the Era of Highly Active Antiretroviral Therapy

To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/μl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up. The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. Mortality, CMV dissemination, retinitis progression, and treatment side effects. Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant. In the HAART era, systemic anti-CMV therapy, while there is immune compromise, seems to provide benefits in terms of longer survival and decreased CMV dissemination. Proprietary or commercial disclosure may be found after the references.

Cause-Specific Life Expectancies After 35 Years of Age for Human Immunodeficiency Syndrome-Infected and Human Immunodeficiency Syndrome-Negative Individuals Followed Simultaneously in Long-term Cohort Studies, 1984–2008

Parametric and semiparametric competing risks methods were used to estimate proportions, timing, and predictors of acquired immune deficiency syndrome (AIDS)-related and non-AIDS-related mortality among individuals both positive and negative for the human immunodeficiency syndrome (HIV) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) from 1984 to 2008 and 1996 to 2008, respectively. Among HIV-positive MACS participants, the proportion of deaths unrelated to AIDS increased from 6% before the introduction of highly active antiretroviral therapy (HAART) (before 1996) to 53% in the HAART era (P < 0.01); the median age of persons who died from non-AIDS-related causes after age 35 years increased from 49.0 to 66.0 years (P < 0.01). In both cohorts during the HAART era, median ages at time of non-AIDS-related death were younger for HIV-positive individuals than for comparable HIV-negative individuals (8.7 years younger in MACS (P < 0.01) and 7.6 years younger in WIHS (P < 0.01)). In a multivariate proportional cause-specific hazards model, unemployment (for non-AIDS death, hazard ratio (HR) = 1.8; for AIDS death, HR = 2.3), depression (for non-AIDS death, HR = 1.4; for AIDS death, HR = 1.4), and hepatitis B or C infection (for non-AIDS death, HR = 1.8, for AIDS death; HR = 1.4) were significantly (P < 0.05) associated with higher hazards of both non-AIDS and AIDS mortality among HIV-positive individuals in the HAART era, independent of study cohort. The results illuminate the changing face of mortality among the growing population infected with HIV.

Ocular lesions in 1,000 consecutive HIV-positive patients in India: a long-term study

BackgroundOcular lesions in patients on highly active antiretroviral therapy (HAART) have shown changes in disease prevalence and pattern. Although they have been described in the Western population, there are not many such studies in the HAART era from India. This study aims to present the clinical profile, systemic correlation, and visual outcome in HIV-positive patients in relation to HAART in comparison with pre-HAART Indian studies and current Western data. Ocular findings and systemic correlation in 1,000 consecutive patients with HIV seen at a tertiary eye care center were analyzed. This study uses a prospective observational case series design.ResultsAge range of the patients was 1.5 to 75 years. Ocular lesions were seen in 68.5% of the patients (cytomegalovirus (CMV) retinitis was the commonest). The commonest systemic disease was pulmonary TB. Mean interval between HIV diagnosis and onset of ocular lesions was 2.43 years. CD4 counts range from 2 to 1,110 cells/mm3. Immune recovery uveitis (IRU) was seen in 17.4%. Interval between HAART initiation and IRU was 4 months to 2.5 years. Recurrence of ocular infection was seen in 2.53% (post-HAART) and > 20% (pre-HAART). Overall visual outcome showed improvement in about 14.3% and was maintained in 71.6% of the patients.ConclusionsCMV retinitis is the commonest ocular opportunistic infection in India, even in the HAART era. Newer manifestations of known diseases and newer ocular lesions are being seen. In contrast to Western studies, in our patients on HAART, ocular lesions do not always behave as in immunocompetent individuals. Ocular TB needs to be kept in mind in India, as well as other neuro-ophthalmic manifestations related to cryptococci, especially in gravely ill patients. Occurrence and frequency of various ocular opportunistic infections in developing nations such as India have significant variations from those reported in Western literature and need to be managed accordingly.