HAART Era Research Articles

HIV infection and suicide in the era of HAART in England, Wales and Northern Ireland

HIV infection and suicide in the era of HAART in England, Wales and Northern Ireland

Treatment and Prevention of Cytomegalovirus-Associated Diseases in HIV-1 Infection in the Era of HAART

Cytomegalovirus (CMV) infection is one of the most common chronic viral infections and is one of the most important opportunistic infections in HIV-infected patients. Although HAART has substantially improved the morbidity and mortality of HIV-infected patients and decreased the frequencies of AIDS-related diseases, opportunistic infections including CMV end-organ diseases still remain a significant clinical challenge. Here we review the clinical manifestation and diagnosis of CMV end-organ diseases including the potential role of CMV infection in the pathogenesis of cardiovascular disease. We explain how HAART has changed the epidemiology of CMV disease in HIV infection and discuss how this influences current treatment guidelines for the prevention of CMV disease and CMV-associated immune recovery syndrome.

Reactive haemophagocytic syndrome in 58 HIV-1-infected patients: clinical features, underlying diseases and prognosis

To describe features of reactive haemophagocytic syndrome (RHS) in HIV-1-infected adult patients. To compare characteristics of patients with malignancy-associated RHS and infection-associated RHS. Retrospective study in three departments of Infectious Diseases/Internal Medicine at three French tertiary centres. Medical charts of HIV-1-infected adult patients and RHS seen between January 2006 and December 2007 were reviewed. Demographic, clinical and laboratory data obtained at the time of RHS episode were compared between patients with malignancy-associated RHS and infection-associated RHS using non-parametric tests. The overall survival was assessed using the Kaplan-Meier method. Fifty-eight HIV-1-infected patients were diagnosed with RHS [certain RHS n = 43, possible RHS n = 15, median (range) age 42 (23-85) years, men 76%]. At time of RHS, the median duration of HIV infection was 4 (0-22) years and 57% received HAART. The median CD4 lymphocyte count was 91 (2-387)/microl and 35% of patients had a plasma HIV-1 RNA less than 50 copies/ml. Underlying haemopathy/malignancy (Hodgkin lymphoma n = 10) or infection (tuberculosis n = 9, cytomegalovirus infection n = 5) were evidenced for 31 and 23 patients, respectively. Patients with haemopathy/malignancy-associated RHS presented more frequently with splenomegaly (97 vs. 70%, P < 0.01), lower aspartate aminotransferase (36 vs. 84 UI/l, P < 0.01) and lactate dehydrogenase (530 vs. 911 UI/l, P < 0.01) levels and CD8 cell count (234 vs. 588/microl, P < 0.01). Eighteen (31%) patients died. The overall survival was not statistically different between the two groups (P = 0.68). In the HAART era, RHS is frequently associated with underlying haemopathy/malignancy, especially Hodgkin lymphoma. The prognosis remains poor but seems, however, better than in the pre-HAART era.

Ten years later: A single hospital experience with malignancy in HIV/AIDS

We present our experience in the era of HAART with 5,112 patients having HIV infection or AIDS, treated between 2002 and 2006 in our hospital, 182 of whom had malignancies (3.56%). We compared our findings to those from a similar cohort of patients studied 10 years earlier. The charts were reviewed and data was electronically collected as in our 1993-1998 study. Similar statistical analyses were performed in both studies and the results were compared. For the current study the average patient age increased by 9 years. A decrease in AIDS-defining cancers (ADC), from 63.6% to 37.3% and a higher incidence of non-AIDS-defining cancers (NADC), 62.7 as opposed to 37.9% was found. No decrease in the incidence of non-Hodgkin's B cell lymphoma (NHL) was noted. There was an increase in the number of opportunistic infections notably hepatitis C virus (HCV) and hepatitis B virus (HBV). HIV/AIDS patients on HAART are older, have lower rates of AIDS related Kaposi's sarcoma and a higher incidence of NADCs than did patients in the early HAART era. No decrease in the proportion of NHL was observed.

Evolution of tuberculosis/HIV co-infection in California during the HAART Era, 1996-2007

2,392 (6%) of 39,718 TB cases during the study period were matched in the state AIDS registry. From 1996 to 2006, annual TB incidence among persons with HIV declined from 368/100,000 to 73/100,000, and without HIV declined from 12.7/100,000 to 7.3/100,000. Comparing the period 1996-2000 with 2001-2007, the proportion of TB/HIV cases increased among Hispanics (48% to 57%; p < .001), foreign born (46% to 63%; p< .001), and women (14% to 18%; p=. 06), and decreased among Blacks (28% to 21%; p < .001). Maleto-male sexual contact (44% to 41%; p < .01) and injection drug use (21% to 15%; p < .01) decreased, and high-risk heterosexual contact (9% to 16%; p < .01) increased as HIV transmission routes. 77% of all foreign born patients with TB/HIV co-infection originated from Mexico or Central America; the median time from immigration to TB diagnosis was 10.7 (IQR 4-19) years. CD4 count at TB diagnosis (median 78 (IQR 30-167)) was available for 54% of patients. Patients with HIV coinfection were more likely to be sputum smear-positive (OR 1.17 (95% CI 1.08-1.28). Both isoniazid resistance (5% to 7%; p=. 07) and pyrazinamide monoresistance (6% to 8%; p = .01) increased over time in TB/HIV cases but not in cases without HIV. In multivariate analysis, Hispanic ethnicity, older age, and injection drug use were inversely associated with treatment success among TB/HIV cases. Discussion In California, the epidemiology of TB/HIV co-infection in the post-HAART era has shifted towards persons of foreign birth, women, Hispanics, and those who acquired HIV through heterosexual sex. In addition, drug resistance has increased in TB/AIDS cases. These changes should be considered in focusing TB and HIV disease prevention and treatment efforts.

Obesity among HIV-infected persons: impact of weight on CD4 cell count.

To assess the effect of obesity on CD4 cell counts, we estimated the association of time-updated BMI categories with CD4 changes among 1001 documented HIV seroconverters. During the pre-highly active antiretroviral therapy (HAART) era, a higher BMI was associated with less reduction in CD4 cell counts over time. However during the HAART era, obese versus normal weight patients had smaller increases in CD4 cell counts (+69 versus +116 cells, P = 0.01). Lower CD4 cell counts may now be another adverse consequence of obesity.

The impact of Kaposi sarcoma and non-Hodgkin lymphoma on mortality of people with AIDS in the highly active antiretroviral therapies era

Background: Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) have strongly diminished in the HAART era, but their impact on life expectancy of people with AIDS (PWA) needs to be monitored. We aimed at quantifying the burden of KS and NHL on mortality of PWA in the HAART period in Italy. Methods: Death certificates of 3209 PWA diagnosed in 1999–2006 who died as of December 2006 were reviewed to identify those deaths in which KS or NHL was the underlying cause. Standardized mortality ratios (SMR) were computed. Results: KS or NHL appeared in 4.3% and 14.6% death certificates, respectively; they were the underlying cause of death in 3.1% and 13.4% of cases. SMR were 8698-fold higher for KS and 349-fold higher for NHL, and tended to decline over the study period. Conclusion: KS and NHL caused about 16% of deaths of PWA in the HAART era, with 100-fold higher risks of death compared to the Italian general population also in recent years. Clinicians and public health officials should be aware of the persisting negative impact of these cancers on life expectancy of PWA.

Diagnóstico, tratamiento y prevención de las alteraciones renales en pacientes con infección por el virus de la inmunodeficiencia humana. Recomendaciones del Grupo de Estudio del Sida/Plan Nacional sobre el Sida

The incidence of opportunistic infections and tumours in HIV-infected patients has sharply declined in the HAART era. At the same time there has been a growing increase of other diseases not directly linked to immunodeficiency. Renal diseases are an increasing cause of morbidity and mortality among HIV-infected patients. In the general population, chronic renal failure has considerable multiorgan repercussions that have particular implications in patients with HIV infection. The detection of occult or subclinical chronic kidney disease is crucial since effective measures for delaying progression exist. Furthermore, the deterioration in glomerular filtration should prompt clinicians to adjust doses of some antiretroviral agents and other drugs used for treating associated comorbidities. Suppression of viral replication, strict control of blood pressure, dyslipidemia and diabetes mellitus, and avoidance of nephrotoxic drugs in certain patients are fundamental components of programs aimed to prevent renal damage and delaying progression of chronic kidney disease in patients with HIV. Renal transplantation and dialysis have also special implications in HIV-infected patients. In this article, we summarise the updated clinical practice guidelines for the evaluation, management and prevention of renal diseases in HIV-infected patients from a panel of experts in HIV and nephrologists on behalf of the Spanish AIDS Study Group (GESIDA) and the National AIDS Plan.

Optimal management of cytomegalovirus retinitis in patients with AIDS.

Cytomegalovirus (CMV) retinitis is the most common cause of vision loss in patients with acquired immunodeficiency syndrome (AIDS). CMV retinitis afflicted 25% to 42% of AIDS patients in the pre-highly active antiretroviral therapy (HAART) era, with most vision loss due to macula-involving retinitis or retinal detachment. The introduction of HAART significantly decreased the incidence and severity of CMV retinitis. Optimal treatment of CMV retinitis requires a thorough evaluation of the patient's immune status and an accurate classification of the retinal lesions. When retinitis is diagnosed, HAART therapy should be started or improved, and anti-CMV therapy with oral valganciclovir, intravenous ganciclovir, foscarnet, or cidofovir should be administered. Selected patients, especially those with zone 1 retinitis, may receive intravitreal drug injections or surgical implantation of a sustained-release ganciclovir reservoir. Effective anti-CMV therapy coupled with HAART significantly decreases the incidence of vision loss and improves patient survival. Immune recovery uveitis and retinal detachments are important causes of moderate to severe loss of vision. Compared with the early years of the AIDS epidemic, the treatment emphasis in the post- HAART era has changed from short-term control of retinitis to long-term preservation of vision. Developing countries face shortages of health care professionals and inadequate supplies of anti-CMV and anti-HIV medications. Intravitreal ganciclovir injections may be the most cost effective strategy to treat CMV retinitis in these areas.

W1431: Gastrointestinal Opportunistic Infections: Usefulness of Colonoscopy in HIV+ Patients With Chronic Diarrhea in the Era of HAART

W1431: Gastrointestinal Opportunistic Infections: Usefulness of Colonoscopy in HIV+ Patients With Chronic Diarrhea in the Era of HAART

197: Renal Prognosis in HIV HCV Co-Infected Patients in the HAART ERA

197: Renal Prognosis in HIV HCV Co-Infected Patients in the HAART ERA

Per-contact probability of HIV transmission in homosexual men in Sydney in the era of HAART

The objective of this study is to estimate per-contact probability of HIV transmission in homosexual men due to unprotected anal intercourse (UAI) in the era of HAART. Data were collected from a longitudinal cohort study of community-based HIV-negative homosexual men in Sydney, Australia. A total of 1427 participants were recruited from June 2001 to December 2004. They were followed up with 6-monthly detailed behavioral interviews and annual testing for HIV till June 2007. Data were used in a bootstrapping method, coupled with a statistical analysis that optimized a likelihood function for estimating the per-exposure risks of HIV transmission due to various forms of UAI. During the study, 53 HIV seroconversion cases were identified. The estimated per-contact probability of HIV transmission for receptive UAI was 1.43% [95% confidence interval (CI) 0.48-2.85] if ejaculation occurred inside the rectum, and it was 0.65% (95% CI 0.15-1.53) if withdrawal prior to ejaculation was involved. The estimated transmission rate for insertive UAI in participants who were circumcised was 0.11% (95% CI 0.02-0.24), and it was 0.62% (95% CI 0.07-1.68) in uncircumcised men. Thus, receptive UAI with ejaculation was found to be approximately twice as risky as receptive UAI with withdrawal or insertive UAI for uncircumcised men and over 10 times as risky as insertive UAI for circumcised men. Despite the fact that a high proportion of HIV-infected men are on antiretroviral treatment and have undetectable viral load, the per-contact probability of HIV transmission due to UAI is similar to estimates reported from developed country settings in the pre-HAART era.

Late diagnosis in the HAART era: proposed common definitions and associations with mortality

To identify a definition of presentation after clinical or immunological disease progression that will reliably identify an individual at high risk of mortality over the first 3 months after HIV diagnosis and that can be adopted as a basis for comparing over time and regions. An observational cohort study. Individuals seen for the first time at a UK Collaborative HIV Cohort study clinic from 1996 to 2006 were identified. Two immunological (CD4 cell count < 200 cells/microl and CD4 cell count <50 cells/microl) and two clinical (AIDS and severe/moderate AIDS) criteria for presentation with advanced HIV disease were compared, as well as combinations of them. The predictive ability of each diagnosis for identifying individuals who died in the first 3 months after HIV diagnosis was assessed. Fifteen thousand seven hundred and seventy-four patients were included, of whom 1495 (9.5%), 4231 (26.8%), 1523 (9.7%) and 379 (2.4%) had a CD4 cell count below 50 cells/microl, CD4 cell count below 200 cells/microl, AIDS or severe/moderate AIDS at diagnosis; CD4 cell counts were unavailable for 2264 (14.4%) patients. Two hundred and six (1.3%) patients died within the first 3 months. Sensitivities of the individual criteria ranged from 18.0% (severe/moderate AIDS) to 50.5% (CD4 cell count < 200 cells/microl) with specificities ranging from 73.5% (CD4 < 200 cells/microl) to 97.8% (severe/moderate AIDS). Combinations of clinical and immunological criteria increased the sensitivity but decreased the specificity. We propose that presentation with 'advanced HIV disease' is presentation with a CD4 cell count below 200 cells/microl or AIDS, whereas 'late' presentation is defined as presentation when the CD4 cell count is below that when treatment should be initiated (currently CD4 cell count < 350 cells/microl or AIDS).

Survival of HIV-infected patients with compensated liver cirrhosis

Since the advent of HAART, liver-related mortality has become the leading cause of non-AIDS deaths in HIV-infected patients in western countries, complications of end-stage liver disease due to chronic hepatitis B, chronic hepatitis C or both being mainly responsible. The incidence and predictors of mortality were examined in HIV-infected patients with compensated liver cirrhosis. The accuracy of three different methods (elastometry, Child-Pugh and Model for End-Stage Liver Disease scores) to predict mortality was further examined. Cirrhosis was defined for hepatic elastometry values above 14.5 kPa. A total of 194 (11.4%) out of 1706 HIV-positive individuals were cirrhotic and were prospectively followed since October 2004 until December 2008. Overall, 89% of cirrhotic individuals had chronic hepatitis C, 10.3% chronic hepatitis B, 4.6% hepatitis delta and 4.1% liver disease of other causes or unknown cause. The overall mortality rate was 5.8 deaths per 100 patient-years. Multivariate analyses showed that age of at least 50 years (hazard ratio 4.76, 95% confidence interval 1.66-13.59, P = 0.004), CD4 cell counts below 200 cells/microl (hazard ratio 3.01, 95% confidence interval 1.26-7.23, P = 0.03) and detectable plasma HIV-RNA (hazard ratio 3.97, 95% CI, 1.53-10.27, P = 0.005) were associated with mortality. A baseline Model for End-stage Liver Disease score of at least 11 (P = 0.03) and hepatic elastometry values above 28.75 kPa (P = 0.001) were independent predictors of mortality. The death rate in HIV-infected patients with compensated liver cirrhosis in the HAART era is 5.8% yearly, higher than mortality previously reported for either HIV-uninfected individuals with cirrhosis or noncirrhotic HIV-positive patients. Factors associated with mortality were older age, low CD4 cell counts and detectable plasma HIV-RNA. Both Model for End-Stage Liver Disease and especially hepatic elastometry accurately predicted mortality in this population.

Progress and Pitfalls in Defining the Influence of Highly Active Antiretroviral Therapy on Human Papillomavirus–Associated Cervical Disease

Progress and Pitfalls in Defining the Influence of Highly Active Antiretroviral Therapy on Human Papillomavirus–Associated Cervical Disease

Opportunistic Infections and IRIS in the Era of HAART

Opportunistic Infections and IRIS in the Era of HAART

Why are patients dying in the HAART Era?

Why are patients dying in the HAART Era?

AIDS-associated mycobacterial infections in a large urban hospital during the HAART era (2003-2006)

AIDS-associated mycobacterial infections in a large urban hospital during the HAART era (2003-2006)

Anal cancers among HIV-infected persons: HAART is not slowing rising incidence.

To evaluate the incidence rates of anal cancer over the HIV epidemic and assess the impact of HAART use on anal cancer events. We evaluated the incidence of and factors associated with anal cancer using longitudinal data from the prospective U.S. Military Natural History Study (1985-2008). Poisson regression and Cox proportional hazard models were utilized. Among 4506 HIV-infected men with 37 806 person-years of follow-up, anal cancer rates (per 100 000 person-years) increased five-fold, from 11 in the pre-HAART to 55 in the HAART era (P = 0.02). Rates continued to increase, reaching 128 in 2006-2008. Persons with HIV infection for more than 15 years had a 12-fold higher rate than those with less than 5 years (348 vs. 28, P < 0.01). At cancer diagnosis (n = 19), median age was 42 years, median CD4 cell count was 432 cells/microl, 74% had a CD4 nadir cell count less than 200 cells/microl, 42% had a prior AIDS event, and 74% had received HAART. From separate models, prior AIDS event (hazard ratio 3.88, P = 0.01) and lower CD4 nadir (hazard ratio 0.85 per 50 cell, P = 0.03) were associated with anal cancer, with a trend for a history of gonorrhea (hazard ratio 2.43, P = 0.07). Duration of HAART use was not associated with a reduced risk of anal cancer (hazard ratio 0.94, P = 0.42). Incidence rates of anal cancer have progressively increased during the HIV epidemic. Persons with a longer duration of HIV infection have a substantially higher rate of anal cancer. As HIV-infected persons are experiencing longer life expectancies and HAART does not appear protective of anal cancer, studies on preventive strategies are needed.

Epidemiology of Hepatitis B virus infection in a US cohort of HIV-infected individuals during the past 20 years.

The epidemiologic trends of hepatitis B virus (HBV) infection in human immunodeficiency virus (HIV)-infected patients over the past 20 years are largely unknown. Prevalence and risk factors for HBV infection overall, at the time of HIV infection, and after HIV infection were examined in an ongoing observational HIV cohort study. Risk factors for HBV infection at the time of diagnosis of HIV infection were evaluated using logistic regression, and risk of incident HBV infection after diagnosis of HIV infection was evaluated using Cox proportional hazards models. Of the 2769 evaluable participants, 1078 (39%) had HBV infection, of whom 117 (11%) had chronic HBV infection. The yearly cross-sectional prevalence of HBV infection decreased from a peak of 49% in 1995 to 36% in 2008 (P < .001). The prevalence of HBV infection at the time of diagnosis of HIV infection decreased during 1989-2008 from 34% to 9% (P < .001). The incidence of HBV infection after diagnosis of HIV infection decreased from 4.0 cases per 100 person-years during the pre-highly active antiretroviral therapy (HAART) era to 1.1 cases per 100 person-years during the HAART era (P < .001); however, this incidence remained unchanged during 2000-2008 (P = .49), with >20% of HBV infections occurring after HIV infection being chronic. Decreased risk of HBV infection after diagnosis of HIV infection was associated with higher CD4 cell count and the use of HBV-active HAART. Receipt of 1 dose of HBV vaccine was not associated with reduced risk of HBV infection after diagnosis of HIV infection. Although the burden of HBV infection overall is slowly decreasing among HIV-infected individuals, the persistent rate of HBV infection after diagnosis of HIV infection raises concern that more-effective prevention strategies may be needed to significantly reduce the prevalence of HBV infection in this patient population.