Highly Active Antiretroviral Therapy Era Research Articles

HIV Infection and Survival of Lymphoma Patients in the Era of Highly Active Antiretroviral Therapy.

Background: Highly active antiretroviral therapy (HAART) has extended the life expectancy of patients with HIV/AIDS to approach that of the general population. However, it remains unclear whether HIV infection affects the survival of patients with lymphoma in the HAART era.Methods: Patients diagnosed with Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, peripheral T-cell lymphoma (PTCL), or follicular lymphoma during 2004-2011 were identified from the National Cancer Database. Survival analyses were conducted, where each HIV-infected patient was propensity score matched to a HIV-uninfected patient on the basis of demographic factors, clinical features, and treatment characteristics.Results: Among 179,520 patients, the prevalence of HIV-infection ranged from 1.0% for follicular lymphoma, 3.3% for PTCL, 4.7% for Hodgkin lymphoma, 5.4% for DLBCL, to 29% for Burkitt lymphoma. HIV infection was significantly associated with inferior overall survival for patients with each lymphoma subtype: Hodgkin lymphoma [HR, 1.47; 95% confidence interval (CI), 1.25-1.74], DLBCL (HR, 1.95; 95% CI, 1.80-2.11), Burkitt lymphoma (HR, 1.46; 95% CI, 1.24-1.73), PTCL (HR, 1.43; 95% CI, 1.14-1.79), and follicular lymphoma (HR, 1.44; 95% CI, 1.04-2.00).Conclusions: HIV/AIDS continues to be independently associated with increased risk of death among patients with lymphoma in the HAART era in the United States, and the association varies by lymphoma histologic subtype.Impact: Examination of effective management strategies for patients with HIV/AIDS-associated lymphoma and enrollment of patients in prospective clinical trials are needed to improve patient outcomes. Cancer Epidemiol Biomarkers Prev; 26(3); 303-11. ©2016 AACR.

Brain and liver pathology, amyloid deposition, and interferon responses among older HIV-positive patients in the late HAART era

BackgroundHIV+ patients on highly active antiretroviral therapy (HAART) with suppressed viral loads have a low incidence of HIV-associated dementia, but increased prevalence of milder forms of HIV-associated neurocognitive disorders (HAND). These milder forms of HAND are often associated with minimal histological abnormalities, and their pathophysiology is unclear. Comorbidities, altered amyloid metabolism, accelerated brain aging, and activated interferon responses are suspected to play a role in HAND pathogenesis in HAART–treated persons.MethodsTo investigate associations between liver disease, accelerated brain aging, and HAND in HIV+ patients in the late HAART era (2002–2015), we studied liver and brain autopsy tissues from 53 older subjects evaluated at UCLA and BWH using histopathological stains, a sensitive fluorescent amyloid stain (AmyloGlo), and targeted gene expression profiling (NanoString).ResultsThe majority of HIV+ subjects (median age 56) were on HAART (89.3%) with last pre-mortem plasma viral load <400 copies/mL (81.5%); 50% had CD4+ counts <200 cells/μL. Compared to HIV- controls (median age 65), HIV+ subjects had more cancer (p = 0.04), illicit drug use (p <0.00001), and HCV co-infection (p = 0.002), less cardiovascular disease (p = 0.03), and similar prevalence of cerebrovascular disease (~40%), hypertension, hyperlipidemia, and diabetes. Deep frontal white matter showed increased gliosis in HIV+ subjects vs. HIV- controls (p = 0.09), but no significant differences in myelin loss, blood vessel thickening, or inflammation. Liver showed more severe fibrosis/cirrhosis (p = 0.02) and less steatosis (p = 0.03) in HIV+ subjects, but no significant differences in inflammation, blood vessel thickness, or pigment deposition. There were no significant associations between liver and brain pathologies. AmyloGlo staining detected large amyloid deposits in only one HIV+ case (age 69 with Alzheimer’s disease pathology) and two HIV- controls (ages 66 and 74). White matter from HIV+ cases vs. HIV- seronegative controls showed a trend (p = 0.06) towards increased interferon response gene expression (ISG15, MX1, IFIT1, IFIT2, and IFITM1).ConclusionsGliosis and cerebrovascular disease, but not accelerated amyloid deposition, are common brain pathologies among older HIV+ patients in the late HAART era. Although HIV+ subjects had more cirrhosis, liver pathology was not associated with any consistent pattern of brain pathology. Cerebrovascular disease, interferon responses, and neuroinflammation are likely factors contributing to brain aging and HAND in older HIV+ patients on current HAART regimens.

Epidemiology of Acquired Immune Deficiency Syndrome and Cerebrovascular Disease in a Post Antiretroviral Era

People with acquired immune deficiency syndrome (AIDS) develop ischemic stroke through distinct mechanisms. These include infections such as syphilis, tuberculosis, varicella, and other conditions such as cocaine abuse, endocarditis, and hypercoagulability. The effect of improved awareness, detection, and treatment with highly active antiretroviral therapy (HAART) on the incidence and outcome of AIDS patients with stroke is unknown. Data from the Nationwide Inpatient Sample from 1995 to 2010 were analyzed. Patients with ischemic stroke and AIDS were identified using ICD-9 (International Classification of Diseases) codes. Time trends for demographics, survival, and frequency of AIDS-associated conditions were analyzed. Proportion of AIDS among stroke patients increased significantly during the study. Median age of all strokes decreased from 75 years in 1995 to 72 years in 2010. Conversely, median age for men with stroke and AIDS increased from 43 years to 53 years; and for women with stroke and AIDS, from 41 years to 51 years. Death rates from stroke in the AIDS patients declined. In recent years, the death rates from stroke are similar to patients without HIV/AIDS. Stroke patients with AIDS had increased odds of syphilis (odds ratio [OR]: 33.50), varicella (OR: 48.34), tuberculosis (OR: 137.48), endocarditis (OR: 5.19), cocaine abuse (OR: 26.05), and hypercoagulability (OR: 4.82). In the HAART era, the median age of incident stroke in AIDS has increased and the mortality from stroke has improved. Research should focus on optimal management of dyslipidemia while on HAART. Whether HAART can reduce the incidence and improve survival of stroke needs to be explored.

Hepatocellular carcinoma in patients with HIV.

Hepatocellular carcinoma (HCC) is becoming an important cause of mortality in patients with HIV, attributed to coinfection with hepatitis C virus, hepatitis B virus, and the longer survival advantage these patients are achieving after introducing the highly active antiretroviral therapy (HAART) regimens. In addition to hepatitis infection, immunosuppression secondary to HIV infection, direct impact of the virus on liver parenchyma, and the use of hepatotoxic antiretroviral drugs, all contribute to HCC pathogenesis. Screening is very important in this particular population; data on population-specific guidelines are still controversial and scarce. Liver transplantation remains the treatment of choice in eligible patients. Trials on sorafenib have not included patients with HIV; yet, we know from small retrospective series that it might be safe and effective. In the HAART era, HCC is arising as a common non-AIDS defining cancer with high impact on morbidity and mortality of HIV-infected patients. Candidates for liver transplantation should be offered this option regardless of HIV infection. Safety and efficacy of sorafenib and other treatment modalities should be further studied and offered as deemed applicable to HIV patients diagnosed with HCC.

Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort

Deaths in HIV-positive people have decreased since the introduction of highly active antiretroviral therapy (HAART) in 1996. Fewer AIDS-related deaths and an ageing cohort have resulted in an increase in the proportion of HIV patients dying from non-AIDS-related disorders. Here we describe mortality and causes of death in people diagnosed with HIV in the HAART era compared with the general population. In this observational analysis, we linked cohort data collected by Public Health England (PHE) for individuals aged 15 years and older, diagnosed with HIV in England and Wales from 1997 to 2012, to the Office for National Statistics (ONS) national mortality register. Cohort inclusion began at diagnosis with follow-up clinical information collected every year from all 220 National Health Service (NHS) HIV outpatient clinics nationwide. To classify causes of death we used a modified Coding Causes of Death in HIV (CoDe) protocol, which uses death certificate data and clinical markers. We applied Kaplan-Meier analysis for survival curves and mortality rate estimation and Cox regression to establish independent predictors of all-cause mortality, adjusting for sex, infection route, age at diagnosis, region of birth, year of diagnosis, late diagnosis, and history of HAART. We used standardised mortality ratios (SMRs) to make comparisons with the general population. Between 1997 and 2012, 88 994 people were diagnosed with HIV, contributing 448 839 person-years of follow up. By the end of 2012, 5302 (6%) patients had died (all-cause mortality 118 per 10 000 person-years, 95% CI 115-121). In multivariable analysis, late diagnosis was a strong predictor of death (hazard ratio [HR] 3·50, 95% CI 3·13-3·92). People diagnosed more recently had a lower risk of death (2003-07: HR 0·66, 95% CI 0·62-0·70; 2008-12: HR 0·65, 95% CI 0·60-0·71). Cause of death was determinable for 4808 (91%) of 5302 patients; most deaths (2791 [58%] of 4808) were attributable to AIDS-defining illnesses. Cohort mortality was significantly higher than the general population for all causes (SMR 5·7, 95% CI 5·5-5·8), particularly non-AIDS infections (10·8, 9·8-12·0) and liver disease (3·7, 3·3-4·2). All-cause mortality was highest in the year after diagnosis (SMR 24·3, 95% CI 23·4-25·2). Despite the availability of free treatment and care in the UK, AIDS continues to account for the majority of deaths in HIV-positive people, and mortality remains higher in HIV-positive people than in the general population. These findings highlight the importance of prompt diagnosis, care engagement, and optimum management of comorbidities in reducing mortality in people with HIV. Public Health England.

Prevalence of anaemia among HIV patients in rural China during the HAART era.

The prevalence of anaemia among HIV patients receiving highly active antiretroviral therapy (HAART) in China has not been extensively studied. The purpose of this study was to estimate the prevalence of anaemia among HIV patients receiving HAART in China. This cross-sectional study was conducted based on data in routine record registers. Factors associated with anaemia were evaluated by logistic regression model. Among the 8632 HIV patients in this analysis, the overall prevalence of anaemia was 39.2%, and the prevalence of mild, moderate, and severe anaemia were 27.2%, 10.8%, and 1.2%, respectively. Anaemia was more prevalence among male, older, little time taken HAART and lower CD4 cell count. Patients taken TCM had lower prevalence of anaemia. The prevalence of anaemia among the HIV patients receiving HAART was high in this study. HIV patients with anaemia who are older and have CD4 cells count lower than 200 cells/mL require more attention. Traditional Chinese medicine may be a potential method to lower the frequency of anaemia.

Opportunistic Infections in HIV-Infected Patients Differ Strongly in Frequencies and Spectra between Patients with Low CD4+ Cell Counts Examined Postmortem and Compensated Patients Examined Antemortem Irrespective of the HAART Era.

ObjectiveAIDS-related mortality has changed dramatically with the onset of highly active antiretroviral therapy (HAART), which has even allowed compensated HIV-infected patients to withdraw from secondary therapy directed against opportunistic pathogens. However, in recently autopsied HIV-infected patients, we observed that associations with a broad spectrum of pathogens remain, although detailed analyses are lacking. Therefore, we focused on the possible frequency and spectrum shifts in pathogens associated with autopsied HIV-infected patients.DesignWe hypothesized that the pathogens frequency and spectrum changes found in HIV-infected patients examined postmortem did not recapitulate the changes found previously in HIV-infected patients examined antemortem in both the pre- and post-HAART eras. Because this is the first comprehensive study originating from Central and Eastern Europe, we also compared our data with those obtained in the West and Southwest Europe, USA and Latin America.MethodsWe performed autopsies on 124 HIV-infected patients who died from AIDS or other co-morbidities in the Czech Republic between 1985 and 2014. The pathological findings were retrieved from the full postmortem examinations and autopsy records.ResultsWe collected a total of 502 host-pathogen records covering 82 pathogen species, a spectrum that did not change according to patients’ therapy or since the onset of the epidemics, which can probably be explained by the fact that even recently deceased patients were usually decompensated (in 95% of the cases, the last available CD4+ cell count was falling below 200 cells*μl-1) regardless of the treatment they received. The newly identified pathogen taxa in HIV-infected patients included Acinetobacter calcoaceticus, Aerococcus viridans and Escherichia hermannii. We observed a very limited overlap in both the spectra and frequencies of the pathogen species found postmortem in HIV-infected patients in Europe, the USA and Latin America.ConclusionsThe shifts documented previously in compensated HIV-infected patients examined antemortem in the post-HAART era are not recapitulated in mostly decompensated HIV-infected patients examined postmortem.

Effect of Advanced HIV Infection on the Respiratory Microbiome.

Previous work found the lung microbiome in healthy subjects infected with HIV was similar to that in uninfected subjects. We hypothesized the lung microbiome from subjects infected with HIV with more advanced disease would differ from that of an uninfected control population. To measure the lung microbiome in an HIV-infected population with advanced disease. 16s RNA gene sequencing was performed on acellular bronchoalveolar lavage (BAL) fluid from 30 subjects infected with HIV with advanced disease (baseline mean CD4 count, 262 cells/mm(3)) before and up to 3 years after starting highly active antiretroviral therapy (HAART) and compared with 22 uninfected control subjects. The lung microbiome in subjects infected with HIV with advanced disease demonstrated decreased alpha diversity (richness and diversity) and greater beta diversity compared with uninfected BAL. Differences improved with HAART, but still persisted up to 3 years after starting therapy. Population dispersion in the group infected with HIV was significantly greater than in the uninfected cohort and declined after treatment. There were differences in the relative abundance of some bacteria between the two groups at baseline and after 1 year of therapy. After 1 year on HAART, HIV BAL contained an increased abundance of Prevotella and Veillonella, bacteria previously associated with lung inflammation. The lung microbiome in subjects infected with HIV with advanced disease is altered compared with an uninfected population both in diversity and bacterial composition. Differences remain up to 3 years after starting HAART. We speculate an altered lung microbiome in HIV infection may contribute to chronic inflammation and lung complications seen in the HAART era.

Transformed occupational prospects for HIV-associated brain syndromes.

We report a case of a full-time worker with late undiagnosed HIV disease presenting as encephalopathy with motor features and a manic-like picture. HIV encephalopathy was a terminal condition before the advent of combination highly active anti-retroviral therapy (HAART). Treatment with HAART, with follow-up in a neuropsychiatric service and rehabilitation involving the occupational health department of his employer, produced a successful return to work. This case demonstrates a remarkable transformation in occupational and other outcomes of HIV-related brain disease in the era of HAART.

Polyomavirus-associated progressive multifocal leukoencephalopathy (PML) in HAART era.

Polyomaviruses may cause human disease, particularly in immunocompromised hosts. JCV, one of the members of polyomaviridae family, is the causative agent of the neurological disease progressive multifocal leukoencephalopathy (PML), which occurs mostly in immunocompromised patients. Progressive Multifocal leukoencephalopathy (PML) is a progressive demyelinating disorder of the central nervous system (CNS) resulting from infection of oligodendrocytes by JC polyomavirus. Whereas after highly active antiretroviral therapy (HAART), the incidence of nearly all of all neurological complication have decreased, this article evaluates the incidence and prognosis of JC polyomavirus-associated PML including a unchangeable incidence of PML associated with JC polyomavirus compared with other opportunistic disease and paradoxical results of disease remission in HAART era.

Socio-demographic and clinical profile of HIV/AIDS patients in HAART era at a tertiary care hospital in North-West Rajasthan, India

Background: To study the socio-demographic and clinical profile of HIV/AIDS patients in HAART Era at a Government tertiary care centre. Methods: The present study was carried out on 300 HIV/ AIDS patients in Department of Ophthalmology in collaboration with ART centre at a govt. tertiary care centre, from the period of February 2015 to November 2015. Patients were studied for their different demographic parameters, clinical spectrum and ocular manifestations of the HIV/ AIDS disease. Results: Age range of study population was 4 years to 73 years, with 57.66% males and 42% females and 0.33% intersex. Majority of the patient’s (82.67%) were in adult (15 to 49 years) age group. Heterosexual contact was the commonest (86.67%) mode of HIV transmission. Most common occupation group, among males was laborers while most of females were house wives accounting for 26.33% and 34% of the study group respectively. Majority of patients belonged to class IV (34.66%) and class III (34.33%) of socioeconomic status. Commonest associated systemic disease was tuberculosis, seen in 14% of patients. Out of total only 9.33% patients had CD4+Tcell count ≤100/mm3, 46.33% of patients were in WHO stage I of HIV/AIDS disease and 78.33% patients were on ART. Conclusions: Majority of patients belonged to low socioeconomic status and in young and productive age group with heterosexual contact being commonest mode of transmission. Majority of our patients were at relatively good immune status, and in early stage of the disease. This shows an impact of early case detection and timely institution of highly active antiretroviral therapy (HAART).

Human Herpesviruses as Copathogens of HIV Infection, Their Role in HIV Transmission, and Disease Progression.

Of eight human herpesviruses (HHVs), often, only herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) find mention in medical literature as both of these viruses are commonly associated with genital lesions and oral ulcers, commonly known as cold sores. However, role of human herpesviruses as copathogens and in aggravation and in the transmission of other human diseases, especially the Acquired immunodeficiency syndrome (HIV/AIDS) has only very recently been recognized. Therefore, screening and treating subclinical HHV infections may offer slowing of HIV infection, disease progression, and its transmission. Beside HSV-1 and HSV-2, HHV-3 a causative agent of herpes zoster remained one of the first manifestations of HIV disease before the era of highly active antiretroviral therapy (HAART). HHV-5 also known as human Cytomegalovirus infection remains a significant risk factor for HIV-associated mortality and morbidity even in HAART era. It is proposed that Cytomegalovirus viremia could be a better predictor of HIV disease progression than CD4+ T-lymphocyte count. The role of HHV-4 or Epstein–Burr virus and HHV-6, HHV-7, and HHV-8 is still being investigated in HIV disease progression. This review provides insight into the current understanding about these 8 HHVs, their co-pathogenesis, and role in HIV/AIDS disease progression. The review also covers recent literature in favor and against administering anti-HHV treatment along with HAART for slower AIDS progression and interrupted sexual transmission.

Cancer incidence and all-cause mortality in HIV-positive patients in Northeastern Algeria before and during the era of highly active antiretroviral therapy.

To assess cancer incidence and all-cause mortality trends in HIV-positive patients in Algeria before and during the highly active antiretroviral therapy (HAART) era. Cross-sectional study. We used hospital-based data of patients with HIV/AIDS between January 1988 and December 2010. Cancer incidence, standardized mortality ratios (SMRs), risk of death, and proportion of HIV-positive patients treated before and during the HAART era were calculated. The joinpoint model was used to assess the magnitude of changes in SMRs. In 1988-2010, 156 patients were diagnosed as HIV-positive. During pre-HAART era, Kaposi sarcoma (KS) incidence was 5%. After the introduction of HAART, KS incidence decreased to 2%. No other AIDS-related cancer was diagnosed during the study. One-third died (52/156), of which 83.6% died in the same year as or in the year after HIV diagnosis; median age at death (interquartile range) was 34.5 (11.8) years. Yearly risk of death declined from 100% in 1998 to 8% in 2010; percentage of patients treated with HAART increased from 13% in 1998 to >80% after 2002. Overall SMR decreased from 200.2 (95% confidence interval [95% CI], 123.2-325.2) before the HAART era to 91.4 (95% CI, 66.0-126.6) thereafter. From 2003, yearly SMRs decreased significantly by 66.1% (P < 0.05) until 2006 but not thereafter. Since 1998, the proportion of HIV-positive patients treated with HAART increased, reaching 84% in 2010, all-cause mortality decreased, and cancer remained rare. However, almost all patients who died during the study seemed to be diagnosed at a late stage of the disease, emphasizing the need for earlier diagnosis of HIV in Algeria.

Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era.

Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4(+) T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons.

Highly active antiretroviral therapy reduces pulmonary IL-8 in HIV-positive women smokers.

Increased levels of the proinflammatory cytokine IL-8 are detected in the sputum of patients with chronic obstructive pulmonary disease (COPD) and during the pathological pulmonary manifestations of HIV infection : To explore a potential interrelationship between smoking, highly active antiretroviral therapy (HAART) and HIV immune status, we collected sputum samples, along with complete pulmonary function tests from groups of HIV-infected women smokers who were either on or off HAART. Analysis of the patient's sputum for cell count along with quantitative measures of IL-8 was performed and correlated with concurrent assessment of pulmonary function test (PFT). We found that HIV-positive smokers had decreased measurements on PFT of the diffusing capacity of the lung for carbon monoxide (D(LCO)) compared to standard reference values that did not differ with HAART usage. HAART, when controlled for CD4, showed a suppressive effect on the levels of pro inflammatory cytokine IL-8 in sputum. We conclude that in the era of HAART, HIV along with concurrent tobacco smoking is associated with declines in PFT in HIV-infected women. The use of HAART in patients appears to mitigate the increases in IL-8 levels in relation to immune status based on CD4 count.

The physical and psychological effects of HIV infection and its treatment on perinatally HIV-infected children.

IntroductionAs highly active antiretroviral therapy (HAART) transforms human immunodeficiency virus (HIV) into a manageable chronic disease, new challenges are emerging in treating children born with HIV, including a number of risks to their physical and psychological health due to HIV infection and its lifelong treatment.MethodsWe conducted a literature review to evaluate the evidence on the physical and psychological effects of perinatal HIV (PHIV+) infection and its treatment in the era of HAART, including major chronic comorbidities.Results and discussionPerinatally infected children face concerning levels of treatment failure and drug resistance, which may hamper their long-term treatment and result in more significant comorbidities. Physical complications from PHIV+ infection and treatment potentially affect all major organ systems. Although treatment with antiretroviral (ARV) therapy has reduced incidence of severe neurocognitive diseases like HIV encephalopathy, perinatally infected children may experience less severe neurocognitive complications related to HIV disease and ARV neurotoxicity. Major metabolic complications include dyslipidaemia and insulin resistance, complications that are associated with both HIV infection and several ARV agents and may significantly affect cardiovascular disease risk with age. Bone abnormalities, particularly amongst children treated with tenofovir, are a concern for perinatally infected children who may be at higher risk for bone fractures and osteoporosis. In many studies, rates of anaemia are significantly higher for HIV-infected children. Renal failure is a significant complication and cause of death amongst perinatally infected children, while new data on sexual and reproductive health suggest that sexually transmitted infections and birth complications may be additional concerns for perinatally infected children in adolescence. Finally, perinatally infected children may face psychological challenges, including higher rates of mental health and behavioural disorders. Existing studies have significant methodological limitations, including small sample sizes, inappropriate control groups and heterogeneous definitions, to name a few.ConclusionsSuccess in treating perinatally HIV-infected children and better understanding of the physical and psychological implications of lifelong HIV infection require that we address a new set of challenges for children. A better understanding of these challenges will guide care providers, researchers and policymakers towards more effective HIV care management for perinatally infected children and their transition to adulthood.

Impact of the highly active antiretroviral therapy era on the epidemiology of primary HIV-associated thrombocytopenia.

BackgroundPrimary HIV-associated thrombocytopenia (PHAT) typically improves with highly active antiretroviral therapy (HAART); however, cases continue to occur. Data comparing the epidemiology of PHAT between the pre-HAART and HAART eras are limited. We retrospectively examined the incidence of PHAT over 28 years in the US Military HIV Natural History Study (NHS) from 1986 to 2013.ResultsSubjects had a nadir platelet count <100 × 109/l with no other identifiable cause. Time periods were categorized as pre-HAART (1986–1995), early HAART (1996–2001), and later HAART (2002–2013). Incidence, demographic data, and CD4 count were compared across the three eras. A generalized estimating equations model was used to assess any association of platelet count and HIV viral load in cases diagnosed during the HAART eras. 218 participants met the case definition. 86.2 % of cases occurred prior to 2002. The incidence of PHAT per 1000 person-years of follow-up was 16.3, 4.6, and 1.9 during pre-HAART, early HAART and later HAART eras respectively. CD4 cell counts were significantly higher in the HAART eras at the time of thrombocytopenia (p < 0.001). Of patients diagnosed after 1996, 96.4 % were viremic within six months preceding the platelet nadir and over half were antiretroviral naïve. Viral load (per log10 copies/ml) inversely correlated with platelet count throughout the HAART eras (p < 0.0001).ConclusionsThe incidence of PHAT has markedly decreased in the HAART era. However, viremic individuals, including those with healthy CD4 cell counts, may be at risk. Achieving viral suppression as early as possible may decrease the incidence further.

Incident Hepatitis B Virus Infection in HIV-Infected and HIV-Uninfected Men Who Have Sex With Men From Pre-HAART to HAART Periods: A Cohort Study.

Men who have sex with men (MSM) are at high risk for hepatitis B virus (HBV) infection. Data on the effect of highly active antiretroviral therapy (HAART) on incident HBV infection in HIV-infected and HIV-uninfected MSM are limited. To determine predictors of incident HBV infection in MSM during pre-HAART and HAART periods. Observational cohort study. Cohort of MSM who have, or are at risk for, HIV infection. 2375 HBV-uninfected MSM in the Multicenter AIDS Cohort Study. Poisson regression was used to compare incidence rates of HBV infection in the pre-HAART and HAART eras and to identify factors associated with incidence of HBV infection. In 25,322 person-years of follow-up, 244 incident HBV infections occurred. The unadjusted incidence rate was higher in HIV-infected MSM than in HIV-uninfected MSM (incidence rate ratio [IRR], 1.9 [95% CI, 1.5 to 2.4]) and was significantly lower in the HAART era than in the pre-HAART era among HIV-infected (IRR, 0.2 [CI, 0.1 to 0.4]) and HIV-uninfected (IRR, 0.3 [CI, 0.2 to 0.4]) MSM. Age younger than 40 years (IRR, 2.3 [CI, 1.7 to 3.0]), more than 1 recent sexual partner (IRR, 3.1 [CI, 2.3 to 4.2]), and HIV infection (IRR, 2.4 [CI, 1.8 to 3.1]) were independently associated with higher incidence of HBV infection, whereas HBV vaccination was protective (IRR, 0.3 [CI, 0.2 to 0.4]). Highly active antiretroviral therapy with HIV RNA levels less than 400 copies/mL was associated with protection (IRR, 0.2 [CI, 0.1 to 0.5]), but HAART in those with HIV RNA levels of 400 copies/mL or greater was not. The observational nature limits inferences about causality. Effective HAART is associated with lower incidence of HBV infection; however, even in the HAART era, incidence of HBV infection remains high among MSM. National Institute of Allergy and Infectious Diseases.

Trends and Predictors of Mortality Among HIV Positive Patients in the Era of Highly Active Antiretroviral Therapy in Uganda.

Knowledge of mortality trends and predictors among HIV-positive patients in the era of highly active antiretroviral therapy (HAART) in resource poor settings is still limited. The aim of this study was to describe trends and predictors of mortality among HIV-positive patients in the era of HAART in Uganda. Data from 2004 to 2013 for adult HIV-positive patients (≥15 years) obtaining care and treatment from the AIDS Support Organization in Uganda were reviewed for mortality. Descriptive statistics were analyzed by frequencies and cross tabulations. Calendar period was used as a proxy measure for HAART exposure and a time plot of the proportion of HIV-positive patients reporting dead per year was used to describe the trends. Logistic regression was used to determine the predictors of mortality at bivariate and multivariate levels, respectively. We included in the analysis 95,857 HIV positive patients; 64% were female with median age of 33 years (interquartile range 27-40). Of these 36,133 (38%) were initiated on ART and a total of 4279 (4.5%) died; 19.5% (835/4279) of those who died had an opportunistic infection. Overall, mortality first increased between 2004 and 2006 and thereafter substantially declined (X2trend=211.9, P<0.001). Mortality was relatively higher in Eastern Uganda compared to other geographical areas. Male gender, older age (>45 years), being from Eastern or Northern Uganda, having none or primary education, being unemployed, advanced immunodeficiency (CD4 count <100 cell/µL or WHO stage III or IV) and underweight (<45 kg weight) at HAART initiation and calendar period 2004-2008 were significant predictors of mortality (P<0.001). Overall, the expanding coverage of HAART is associated with a declining trend in mortality among HIV positive patients in Uganda. However, mortality trends differed significantly by geographical area and men remain potentially at higher risk of death probably because of delayed initiation on ART. There is urgent need for men targeted interventions for improved ART performance.

Incidence Rate and Risk Factors for Contralateral Eye Involvement among Patients with AIDS and Cytomegalovirus Retinitis Treated with Local Therapy

Purpose: To calculate the incidence of, and to identify the risk factors for developing contralateral eye involvement among patients with AIDS and unilateral cytomegalovirus retinitis (CMV retinitis), who were treated, in the era of highly-active antiretroviral therapy (HAART), with repetitive intravitreal ganciclovir injections.Materials and Methods: The clinical records of 119 patients were included. The main outcome measurement was the occurrence of contralateral eye involvement.Results: Over a mean follow-up period of 1.6 years, the overall incidence rate of contralateral involvement was 0.17/person-year. The cumulative incidence of contralateral involvement at 6 months and 1 year was 23.8% and 28.4%, respectively. Receiving HAART at the visit before the event was associated with a decreased risk of developing contralateral retinitis (hazard ratio [HR] = 0.26, P = 0.002).Conclusions: The use of HAART, associated with subsequent immune recovery, significantly reduced the incidence of contralateral eye involvement by approximately 75% among patients in our setting.