Availability Of Highly Active Antiretroviral Therapy Research Articles

Cardiovascular complications in the acquired immunodeficiency syndrome

The introduction of highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of HIV disease, with increased survival rates. However, the introduction of HAART has generated a contrast in the cardiac manifestations of AIDS. In developed countries, we observed an approximate 30% reduction in the prevalence of HIV-associated cardiomyopathy, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availability of HAART is limited and the pathogenic impact of nutritional factors is significant, we observed an increase of approximately 32% in the prevalence of HIV-associated cardiomyopathy and a related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, have been shown to cause, in a high proportion of HIV-infected patients, a iatrogenic metabolic syndrome (HIV-lipodystrophy syndrome).This is associated with an increased risk of atherosclerosis-related cardiovascular events even in young HIV-infected people. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce cardiovascular risk in HIV-infected patients receiving HAART.

British HIV Association guidelines for HIV‐associated malignancies 2008

British HIV Association guidelines for HIV‐associated malignancies 2008

Contribution of metabolic and anthropometric abnormalities to cardiovascular disease risk factors.

Patients with human immunodeficiency virus (HIV) infection have sustained alterations in metabolism (lipids and insulin/glucose homeostasis) and body composition (fat distribution) that are proatherogenic (the Figure). HIV infection itself and/or its therapies may contribute to these alterations (the Table); although most effects are reversible, there are some possibly irreversible consequences of treatment. With the relative restoration to health seen in the era of highly active antiretroviral therapy (HAART), many traditional risk factors and promoters of dyslipidemia and diabetes also are present; they interact with HIV-specific inducers to worsen dyslipidemia and to increase the prevalence of insulin resistance and diabetes. Figure. Overview of the effects of HIV and its therapies on CVD risk. The contribution of traditional risk factors must be kept in mind, and they may occur with increased prevalence in people with HIV infection (eg, smoking). HIV, likely through the inflammatory response, and antiretroviral therapies independently affect many of the mediators of CVD risk. The effects on lipids are a prominent but complex example; HIV infection lowers LDL levels, but antiretroviral therapy raises LDL back up to normal levels. The bidirectional arrows indicate associations, but there is not yet adequate proof of causality. The dotted arrow between body composition and CVD indicates that body fat is known to affect the mediators such as dyslipidemia and insulin resistance but may also have a direct effect. FFA indicates free fatty acids; ARV, antiretroviral. View this table: Table. Effects of HIV Treatment These disturbances in lipid and glucose metabolism and renal disease may contribute, at least in part, to the excess cardiovascular disease (CVD) morbidity and mortality observed in HIV-infected individuals (the Figure). However, the relative contribution to excess CVD risk of traditional CVD risk factors, especially smoking, compared with these infection- and treatment-specific complications requires clarification. More prospective data with multivariable modeling are needed. …

Pneumocystis jiroveci Pneumonia in Patients With AIDS in the Inner City: A Persistent and Deadly Opportunistic Infection

Highly active antiretroviral therapy (HAART) has decreased the morbidity and mortality of opportunistic infections including Pneumocystis jiroveci pneumonia (PCP) among HIV-infected individuals. We performed a hospital-based retrospective cohort study among a population of medically underserved inner city persons living in Atlanta, Georgia, diagnosed with confirmed PCP to compare the epidemiology and outcomes of PCP during 2 defined periods: 1990 to 1995, or pre-HAART period, and 1996 to 2001, or HAART period. A total of 488 patients were available for analysis. The overall mortality rate was 47% during the pre-HAART era compared with 37% during the HAART era (P = 0.02). However, among those patients that required medical intensive care unit admission and mechanical ventilation, the mortality rate was particularly high, with over 80% of patients dying as a result of their episode of PCP during both periods. PCP was the initial presentation of HIV infection in 39.3% in the pre-HAART period with a mortality rate of 52%, in contrast with 37% in the HAART period, with a mortality rate of 45%, respectively (P = NS). Only 30.7% in the pre-HAART period and 31.1% of patients in the HAART period were receiving PCP prophylaxis. The overall risk of death, when we combined both groups in the analysis, was higher for those patients who did not take PCP prophylaxis, those who smoked tobacco, and those who were admitted to the medical intensive care unit and required mechanical ventilatory support. Our findings suggest that despite the availability of HAART, PCP continues to cause a significant burden of disease among inner-city HIV-infected populations.

Bystander Effects

Bystander Effects

Contribution of HIV to Mortality Among Injection Drug Users in the Era of HAART

To the Editor: Improving access to antiretroviral therapy among HIV-infected injection drug users (IDUs) is an urgent international priority,1,2 and several international initiatives, including the WHO's 3 × 5 Initiative,3 are seeking to improve use of antiretroviral therapies among IDUs. In an earlier report from our setting, which considered follow-up until May 2000, it was noted that only the minority of deaths among IDUs were due to HIV infection, and the free availability of highly active antiretroviral therapy (HAART) was posited as a potential explanation for low HIV/AIDS mortality.4 Because the local setting of free HAART provides a somewhat unique opportunity to examine the impact of HIV on mortality where financial barriers to HIV/AIDS care do not exist,5 the present study was conducted to compare updated mortality rates among HIV-infected and HIV-uninfected injection drug users since the local guidelines were changed to restrict all initial antiretroviral regimens to triple therapy.6 Beginning in May 1996, persons who had injected illicit drugs in the previous month were recruited into the Vancouver Injection Drug Users Study (VIDUS).7 As previously described,7 at baseline and then semiannually, a trained nurse-interviewer administers a questionnaire regarding health status and health care utilization. Upon recruitment into the study, IDUs provided a venous blood sample for testing of HIV serology, and a trained research nurse conducted an interviewer-administered questionnaire. The baseline for the present study was restricted to July 1, 1997, because this is the date that the province's therapeutic guidelines were amended to recommend that all antiretroviral regimens consist of triple therapy, rather than the dual therapy regimens that were allowed before this date.6 We calculated the cumulative mortality rates among baseline HIV-infected versus HIV-uninfected participants using Kaplan-Meier methods. As described previously, deaths were determined through a linkage with the province's Vital Statistics agency.1 We also calculated the unadjusted and adjusted relative hazards of mortality using Cox proportional hazards regression. Here, all behavioral variables and HIV status were treated as time-updated covariates based on semiannual follow-up data. For the multivariate model, a fixed model was built that adjusted for those variables that were found to be P < 0.05 in univariate analyses. We considered the following variables: age, gender, ethnicity (Aboriginal vs. other), neighborhood residence, hepatitis C infection, daily cocaine use (yes vs. no), and daily heroin use (yes vs. no). Analyses were conducted using SAS 8.0 (SAS Institute, Cary, NC); the threshold for statistical significance was set at P < 0.05. All P values were 2-sided. Between July 1, 1997, and November 30, 2005, 1441 individuals were recruited into the VIDUS cohort, among whom 295 were baseline HIV-positive and 136 became HIV-infected during follow-up. Overall, the cumulative mortality was 11.75% by 4 years. As shown in Figure 1, the cumulative mortality rate was 23.29% for HIV-infected individuals and 8.09% for uninfected individuals (log-rank P < 0.001). As also shown here, whereas the pattern of mortality was more similar early during follow-up, in recent years a large differential in mortality has emerged. In Cox regression, HIV infection was associated with elevated mortality in both univariate (relative hazard: 3.54, 95% confidence interval [CI]: 2.75 to 4.55; P < 0.001) and multivariate analyses (relative hazard: 3.63, 95% CI: 2.78 to 4.71; P = 0.001). The final model was adjusted for age (P < 0.001), ethnicity (P = 0.074), neighborhood residence (P = 0.001), and hepatitis C status (P = 0.514).FIGURE 1: Mortality rates stratified by baseline HIV status.The generalizability of prospective cohort studies of marginalized populations such as IDUs is limited, in that it is often difficult to know whether the population is similar to the overall community. Prior studies have suggested that the VIDUS cohort is representative of IDUs in the community.4 The present study indicates that a large and growing contribution of HIV to mortality among IDUs has emerged despite the free availability of HAART to all IDUs through a universal health care system. Although mortality rates were more similar between HIV-infected and HIV-uninfected IDUs several years ago in our setting,4 the large difference in mortality that has emerged demonstrates a growing need for interventions to improve access and adherence to HAART among IDUs. Ryan Blades, BA* Kathy Li, PhD* Thomas Kerr, PhD*† Mark W. Tyndall, MD, ScD, FRCPC*† Julio S. G. Montaner, MD, FRCPC, FCCP*† Evan Wood, MD, PhD*† *BC Centre for Excellence in HIV/AIDS St. Paul's Hospital, Vancouver †Department of Medicine University of British Columbia, Vancouver ACKNOWLEDGMENTS The authors wish to thank the participants in the VIDUS study and the VIDUS staff. This study was made possible through support from CANFAR, CIHR, and the U.S. NIH. We thank Deborah Graham and Caitlin Johnston for their research assistance.

Cytomegalovirus Retinitis: The Neglected Disease of the AIDS Pandemic

Cytomegalovirus (CMV), a member of the herpesvirus family, was a familiar cause of blindness and death in patients with advanced AIDS in Western countries prior to the introduction of highly active antiretroviral therapy (HAART). CMV retinitis then occurred in roughly one-third of patients with AIDS, and accounted for over 90% of cases of HIV-related blindness [1]. Extraocular CMV disease was a major cause of AIDS-related morbidity and mortality [2]. CMV retinitis is now clinically infrequent in patients with AIDS in developed countries, thanks to the widespread availability of HAART, although the problem has not disappeared [3,4]. Successful fundamentals of management are screening eye examinations in patients with low CD4 counts, and effective anti-CMV treatment with ganciclovir and related compounds, combined with HAART. In developing regions of the world where the HIV/AIDS pandemic is rapidly unfolding, CMV retinitis is a neglected disease, largely undiagnosed and untreated. Workable diagnostic and therapeutic strategies have not yet been defined, and CMV is absent from current and pending World Health Organization (WHO) guidelines for the management of HIV in resource-limited settings. Similarly, the WHO’s ambitious “Vision 2020” program, which seeks to provide guidance on the use of ophthalmologic resources until the year 2020, fails to mention CMV retinitis. The scale of the CMV problem in developing regions is still not known, as most cases of CMV retinitis are never diagnosed. Routine retinal examination is rarely performed and the diagnosis may not be considered unless a patient has damaged vision, or even becomes irreversibly blind. Mortality due to extraocular CMV disease is almost impossible to attribute without autopsy, and so is wrongly ascribed, usually to “advanced HIV infection” or tuberculosis. Yet it has been estimated that “between 5% and 25% of all HIVinfected patients in the developing world can be expected to develop this blinding disorder at some point during the course of their illness” [5], leading some to warn of a possible “epidemic of blindness” [6]. Recent direct evidence for the substantial scope of this neglected problem comes from a tertiary care ophthalmology center in Chang Mai, Thailand, where in a large consecutive series of referrals, 19% of the cases of bilateral blindness were caused by CMV retinitis, following only cataract as a cause of blindness, and exceeding glaucoma, age-related macular degeneration, and diabetic retinopathy [7]. In this article we provide preliminary data describing the problem and suggest possibilities for management of CMV retinitis in resource-poor settings. Our observations are based on the clinical experience from Medecins Sans Frontieres (MSF) HIV/AIDS projects in Cambodia, South Africa, Lesotho, Myanmar, Thailand, and China, and on field assessments of four of these programs, and other programs at other locations, by the corresponding author (DH), an ophthalmologist with clinical training and experience with uveitis and CMV retinitis. Epidemiology In developing countries CMV infection is usually acquired in childhood, and nearly 100% of adults are seropositive [8,9,10]. Like other herpesvirus infections, CMV may remain latent for life. Overt clinical disease occurs with waning immunity.

Living and working with HIV in France in 2003: results from the ANRS-EN12-VESPA Study

The employment rate of people living with HIV in France remains lower than in the general population despite HAART (highly active antiretroviral therapy) availability, translating into a high disease-related socioeconomic burden. Our objective was to investigate the relationships between HIV disease and employment status. We used data from the ANRS-EN12-VESPA Study. Analyses were restricted to the 2750 working-aged (<60 years) participants. Individuals' health characteristics were compared according to employment status and plans of access/return to work, using logistic regression models to account for sociodemographic/occupational and health characteristics. The employment rate was 56.5%; 44.9% of participants had remained employed since diagnosis and 11.6% had accessed employment after diagnosis. Compared with unemployed participants, those who had maintained employment were less likely to be of fair/poor health and have a history of AIDS and hepatitis C virus co-infection, were more likely to have been diagnosed with HIV after 1996, have a history of HIV-related hospitalization and a CD4 cell count of 200 cells/microl or less. Among employed participants, 70.1% had not disclosed their HIV status at the workplace and 8.5% reported HIV-related adjustments in their working conditions. Among the unemployed, 64.5% reported plans of access/return to work and 58.2% of those had attempted to do so. Motivations for access/return to work were mainly of a social, psychological and financial nature. The employment status of people living with HIV/AIDS is associated with sociodemographic/occupational factors in addition to health characteristics. Management of HIV infection at work remains a challenge in the HAART era.

Overview of HIV drug resistance and its implications for China

At the end of 2005 an estimated 650 000 people in China were infected with HIV among whom 75 000 were in need of ART. The Division of Treatment and Care at the National Center for AIDS/STD Control and Prevention (NCAIDS) Chinese Center for Disease Control (CCDC) has been responsible for the overall scale up of the National Free ART Program. As of December 2005 a total of 20 453 patients in 28 provinces autonomous regions and special municipalities had benefited from this national program and received free ART. The increase in access to ART however is accompanied by the risk of drug resistance development. A small body of literature already documents HIV drug resistance in China in these treated populations. These preliminary findings are consistent with the development of drug resistance observed in developed countries soon after the initiation of wide-scale HIV treatment. Therefore it is imperative that clinicians understand the causes and implications of HIV resistance in both patientcare and in the public health perspective. (excerpt)

Antiretroviral Therapy for Children

ACCORDING TO THE UNITED NATIONS PROGRAMME on HIV/AIDS (UNAIDS) global report on human immunodeficiency virus (HIV), in 2005 more than 2.3 million children were living with HIV infection, and 380 000 children with HIV had died. Most of the children who die from HIV have severe manifestations of common childhood illnesses, such as diarrhea, malnutrition, acute respiratory tract infection, and tuberculosis. These children often die before the diagnosis of HIV infection can be made, and mortality is often attributed to a background high rate of early childhood mortality. The United States is home for a diminishing proportion of HIV-infected children, with an estimated 11 000 cases in 2005. There are 2 reasons for this decreasing population of HIV-infected children in the developed world. First, pregnant women are increasingly being offered HIV testing, and HIV-infected women are receiving antiretroviral medications sufficient to reduce transmission to a rate of approximately 1% to 2%. Second, the population of HIV-infected children is diminishing because those children who had been infected are now growing up and becoming adults, following the introduction of potent new drugs in 1996. According to a longitudinal study by the Pediatric AIDS Clinical Trials Group (PACTG 219), the mortality rate for HIVinfected children and adolescents decreased from more than 5% in 1996 to less than 1% in 1998. Similar survival benefits have been observed among adults. The impact of highly active antiretroviral therapy (HAART) on survival and quality of life among patients affected by HIV is hardly disputable, but concise objective evidence of the benefit of treatment on infectious complications in children has been lacking in the medical literature. Before the availability of HAART, opportunistic infections such as Pneumocystis jiroveci pneumonia, bacteremia, bacterial pneumonia, and fungal sepsis were significant fatal diseases in patients infected with HIV and remain so among patients not receiving therapy. In this issue of JAMA, Gona and colleagues provide objective evidence to substantiate the benefit of HAART or, more correctly, the association of HAART and opportunistic infection prophylaxis with incidence of opportunistic infections before and after the advent of HAART. In a retrospective cohort study, Gona et al compared the incidence of 29 opportunistic infections in HIV-infected children who were treated in the HAART era with the incidence among those who were treated before the availability of HAART. They found that the incidence of P jiroveci pneumonia had decreased by 14-fold, disseminated Mycobacterium avium complex by 12-fold, bacteremia by 10-fold, and bacterial pneumonia by 5-fold. These reductions in opportunistic infections occurred despite a concomitant reduction in the use of specific prophylaxis medications, suggesting that immune reconstitution rather than improved prophylaxis was primarily responsible for better outcomes. The size and diversity of the population studied allows for generalizability of the results to the US population of children with HIV infection. There were approximately 3000 children in the cohort, which constitutes about 22% of children and adolescents living with HIV in the United States. Given the diminishing population of HIV-infected children, it is unlikely that additional data will become available in this country. There were limitations with the retrospective cohort study design, which evaluated available data from a database. Some events and clinical practices changed over time and could have affected case ascertainment and overall disease incidence. Although the incidence of bacterial pneumonia was reported, the diagnosis of this problem in children is difficult, because no consistent clinical or radiographic features reliably distinguish different etiologies of pneumonia. Radiographic pneumonia may or may not be associated with bacteremia. When such an association occurs, the relationship is not always a causal one. Specific etiologic diagnosis of bacterial pneumonia can be determined by diagnostic techniques, such as lung aspirates or bronchoalveolar lavage. These procedures are highly sensitive but are seldom used because they are considered too invasive.

RISK FACTORS FOR FOLLOW-UP INTERRUPTION OF HIV PATIENTS IN FRENCH GUIANA

French Guiana is the region of France where the HIV epidemic is most prevalent. To determine the risk factors for being lost for follow-up, we followed a cohort of 1,213 patients between 1992 and 2002 and determined which variables were related to two definitions of being lost to follow-up: permanently disappearing from HIV clinics and coming back after more than 1 year of missed appointments. The incidence rate for permanent follow-up interruption was 17.2 per 100 person-years. The median time to lost to follow-up was 4.3 years (interquartile range = 1.4-8.4 years). Cox modeling showed that the younger age groups, foreigners, patients with initial CD4 counts at the time of HIV diagnosis less than 500/mm3, and patients followed before the availability of highly active antiretroviral therapy (HAART) were significantly more likely to be permanently lost to follow-up, suggesting that some of the patients may have died. When looking at temporary loss to follow-up, younger age groups, untreated patients, patients consulting before the availability of HAART, and patients with CD4 counts more than 500/mm3 were more likely to not come back for a period of more than 1 year.

The search for social validation and the sexual behavior of people living with HIV in Rio de Janeiro, Brazil: Understanding the role of treatment optimism in context

The primary aim of this qualitative study was to explore the influence of HIV treatment optimism on the sexual behavior of people living with HIV/AIDS (PLWHA) receiving highly active anti-retroviral therapy (HAART) at public health clinics in Rio de Janeiro, Brazil. We also explored the psycho-social dynamics of participants’ sexual relationships in order to understand more broadly how these factors influence the sexual behavior of PLWHA and how they shape HAART-related beliefs. Twenty-three semi-structured, in-depth interviews were conducted with three groups: heterosexual women, heterosexual men and men who have sex with men living with HIV who reported being sexually active in the last year and were currently receiving HAART. We found that the availability of HAART was conceptualized as a rationale for unsafe sex among a minority of study participants and that this was more common among men than among women. Specific examples of treatment optimism appeared to be employed as a means to avoid acknowledging how deeper psychosocial issues may have been influencing participant's sexual behavior. Most participants’ sexual behavior appeared largely to be a product of their desire for social validation and linked to feelings of shame and denial, including but not limited to HIV. Participants from all three groups expressed a considerable amount of fear and/or anxiety regarding behaviors such as disclosure and condom use as a result of the unexplored conflict between implementing these behaviors and continuing with their strategies for social validation within the context of their sexual relationships. We conclude that short-term information, education and communication interventions surrounding treatment optimism, disclosure and condom use are appropriate and necessary; but that they are not sufficient to address the core challenges to unsafe sex among PLHWA. These deep-rooted psychosocial issues may be better addressed by longer-term individual and group-level opportunities for exploration and critical reflection regarding sense of self and its relationship to social solidarity among PLWHA.

HIV-Associated Myocarditis

HIV-associated myocarditis may be defined as ‘‘a process characterized by a lymphocytic infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of the ischemic damage associated with coronary artery disease in subjects infected by HIV with or without evidence of opportunistic infective agents’’ [1,2]. Myocarditis has been documented at autopsy in 40% to 52% of patients who died of AIDS before the introduction of highly active antiretroviral therapy (HAART). According to a 5-year clinical echocardiographic study performed by the Gruppo Italiano per lo Studio Cardiologico dei pazienti affetti da AIDS (GISCA) [1], involving 952 HIV-infected patients, myocarditis had a prevalence of 8% (76 of 952) with an annual incidence of left ventricular dysfunction of 1.5%. In the GISCA autopsy series histologic diagnosis of myocarditis was made in 30 (37%) of 82 patients with cardiac involvement [2]. Of 12 autopsy patients with dilated cardiomyopathy, 10 (83%) had active myocarditis at histologic examination [2]. These data are in agreement with those previously reported by Herskowitz and coworkers [3], who detected myocarditis in endomyocardial biopsy specimens from 15 (40%) of 37 patients with symptomatic left ventricular dysfunction. Although there is no evidence from prospective studies to suggest that HAART has a beneficial effect on HIV-associated myocarditis, some retrospective studies suggest that by improving the immunologic state of the patients and reducing the incidence of opportunistic infections, HAART might reduce the incidence of myocarditis by about 33% [4,5]. The median incidence of HIV-associated myocarditis is increasing in developing countries (about 32%), however, where the availability of HAART is limited and the pathogenetic impact of nutritional factors is greater [6]. Pathology

Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men

The incidence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of highly active antiretroviral therapy (HAART). The prevalence of the putative anal cancer precursor, anal intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced. We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART. A baseline point-prevalence analyses in a prospective cohort study of AIN was performed at a university-based research clinic. A total of 357 HIV-positive MSM with no history of anal cancer completed a questionnaire detailing behaviors and medical history, anal cytology and human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsy for detection of AIN. Eighty-one percent of participants with available CD4+ cell counts at baseline had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95% confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were associated with AIN after adjustment for length of time participants were HIV-positive, CD4+ cell count and HIV viral load. The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART. Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART.

Recent Advances in Acquired Immunodeficiency Syndrome (AIDS)-related Lymphoma

Human immunodeficiency virus-infected patients are at an increased risk for developing both Hodgkin and non-Hodgkin lymphoma when compared with the general population. With the remarkable decrease in the incidence of opportunistic infections since the availability of highly active antiretroviral therapy (HAART), acquired immune deficiency syndrome-related lymphoma (ARL) is now the second most common cancer associated with human immunodeficiency virus after Kaposi sarcoma. Over the last few years, advances in our understanding of the molecular biology of this heterogeneous group of lymphomas have led to the adoption of new classification systems. The prognosis of patients with ARL has improved dramatically with the availability of HAART, and the survival of many of these patients is now comparable to patients in the general population. Apart from the contribution of HAART, this improvement in prognosis can also be attributed to new initiatives in treatment of these patients, such as the use of effective infusional regimens, the feasibility of high-dose therapy with peripheral stem cell rescue for relapsed or refractory disease, and better supportive care. Nonetheless, several controversial issues persist, including the optimal timing of HAART with combination chemotherapy, the role of rituximab when incorporated into treatment regimens, and the optimal therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma. This article reviews the changes in the epidemiology of ARL in the era of HAART, advances in the biology of ARL, new developments in the management of patients with ARL, and several of the controversial issues that oncologists may encounter in the care of these patients.

Ocular association of HIV infection in the era of highly active antiretroviral therapy and the global perspective

Ocular involvement is a common complication of HIV infection. Since the late 1990s, widespread use of highly active antiretroviral therapy (HAART) has altered the spectrum, and reduced the incidence of ocular involvement in developed countries. The incidence of the most common ocular opportunistic infection, cytomegalovirus retinitis, has decreased tremendously. However, immune recovery uveitis secondary to HAART has emerged as a frequent visually threatening condition. Early diagnosis and treatment with periocular steroids is helpful in minimizing visual loss. Clinicians should also be aware that certain antimicrobial agents used to treat opportunistic infections in HIV-positive patients are associated with potentially serious ocular side effects. In developing countries, where most of the world's 40 million HIV-positive patients live, the spectrum and incidence of ocular involvement differ from those in developed countries. The lack of HAART availability is among the many causes of these differences, which may include nutritional factors, basic medical care availability and the levels of exposure to different infectious agents. These factors add to the already challenging task of treating ocular complications and preventing blindness in HIV-positive patients in developing countries.

Incidence of Sexually Transmitted Diseases and HIV Infection Related to Perceived HIV/AIDS Threat Since Highly Active Antiretroviral Therapy Availability in Men Who Have Sex With Men

Concerns have been expressed regarding increase in risky sex because of the availability of antiretroviral treatments in Western countries. The goal of this longitudinal study was to investigate the association between highly active antiretroviral therapy (HAART)- and postexposure prophylaxis-related beliefs and the incidence of sexually transmitted diseases (STDs) and new HIV infections in men who have sex with men (MSM). Data on the incidence of STDs and new HIV infection, and the level of agreement with different HAART- and PEP-related beliefs from 151 HIV-negative MSM were compiled. Of all MSM, 65.6% tested negative for any STDs and 7 men HIV seroconverted. Perceiving less HIV/AIDS threat since HAART availability and younger age were significantly associated with a higher incidence of STDs. Perceiving less need for safe sex since HAART availability was significantly associated with an increased likelihood of HIV seroconversion. The results support the assumption that there is an association between the incidence of STDs and a decreased perception of HIV/AIDS threat resulting from HAART availability. Less perceived need for safe sex since HAART availability was associated with HIV seroconversion.

An Extremely Different Dysmetabolic Profile Between the Two Available Nonnucleoside Reverse Transcriptase Inhibitors: Efavirenz and Nevirapine

An Extremely Different Dysmetabolic Profile Between the Two Available Nonnucleoside Reverse Transcriptase Inhibitors: Efavirenz and Nevirapine

Changes in the AIDS epidemiologic situation in Puerto Rico following health care reform and the introduction of HAART

To compare the occurrence of AIDS as well as the sociodemographic and clinical profiles of AIDS patients in Puerto Rico before and after the introduction of highly active antiretroviral therapy (HAART) and the privatization of the island's public health care system. We compared the incident AIDS cases for two three-year periods, 1992-1994 and 1998-2000, in four populations: (1) entire United States, (2) Puerto Rico, (3) Bayamón Health Region (located in north-central Puerto Rico, it includes 11 of the island's 78 municipalities), and (4) an HIV cohort enrolled at the Universidad Central del Caribe (UCC) School of Medicine. The UCC is located in Bayamón, Puerto Rico, within an academic medical complex that houses the teaching hospital (Ramón Ruíz Arnaú University Hospital), the ambulatory health care facilities (Immunology Clinics) for patients with HIV, and administrative buildings. This represents the major government-sponsored health care infrastructure within the Bayamón Health Region. Incident AIDS declined substantially between the two periods in each of the four populations studied. The 48.1% decline in Puerto Rico exceeded the 40.9% decline in the United States. The decline in Puerto Rico likely resulted from increased availability and implementation of HAART and the delivery of health care to HIV/AIDS patients in an integrated fashion within each regional ambulatory clinic. In spite of this improvement, the absolute number of patients with AIDS on the island remains high. Substantial resources for treatment and prevention are required. The proportion of new AIDS cases was lower among women, persons 40 years of age or older, the less educated, and those living alone. Injection drug use remains the predominant mode of transmission in Puerto Rico. Further gains in Puerto Rico's fight against AIDS will depend on the island's ability to reduce the transmission that occurs through injection drug use; the use of HAART on a larger number of vulnerable patients, particularly intravenous drug users; educational interventions to improve medication compliance in certain risk groups; and specific measures aimed at decreasing the rate of injection drug use.

HIV dementia: an evolving disease

Several advances have led to improvements in the care and prognosis of HIV+ individuals. The first is an understanding of the direct relationship between HIV replication and subsequent immunological and clinical progression, reinforcing the need to completely suppress HIV replication to control disease progression. The second is the wider availability of HAART which can provide effective suppression of HIV. The third major change is the ability to monitor HAART through the reliable and widespread measurement of plasma HIV RNA levels, which has become a routine part of clinical care. Since the introduction of highly active antiretroviral therapy (HAART) in the 1990s, there have been significant declines in the incidence rates of opportunistic infections in developed countries. HAART has clearly improved survival for individuals with HIV/AIDS, and has reduced the incidence of HIV-associated dementia (HIV-D) by 40–50% ( Brodt et al., 1997; Sacktor et al., 2001a,b). The prevalence of sensory neuropathies in advanced HIV/AIDS now exceeds 20% ( Schifitto et al., 2002), and may rise further with prolonged exposure to neurotoxic HAART. HIV-D and HIV-related sensory neuropathies (HIV-SN) have a combined prevalence of about 30–50% in advanced HIV disease, suggesting that HAART does not provide complete protection against neurological damage ( Bouwman et al., 1998). HIV-associated dementia (HIV-D) remains a common cause of dementia worldwide, and with HIV-related sensory neuropathies (HIV-SN) represents the commonest neurological disorders associated with AIDS. Furthermore, the temporal progression of HIV-D appears to have been altered by HAART, with most patients now showing an attenuated form of dementia, which with treatment is slowly progressive or static ( Dougherty et al., 2002). This overview will review some of the outstanding questions relating to HIV-dementia, including: (a) are there differing phenotypes or temporal patterns of progression in HIV-dementia? (b) what determines these temporal patterns? and (c), what has been the impact of therapy on HIV dementia?