Detection of latent tuberculosis among HIV-infected patients after initiation of highly active antiretroviral therapy

This cross-sectional study of 110 individuals examined skin testing for latent tuberculosis infection (LTBI) after the initiation of highly active antiretroviral therapy. Skin test reactivity to one or more of four antigens was found in 98 out of 110 subjects (89%), and was maximal in those whose CD4 cell counts recovered to >= 100 cells/mm3. Skin testing is reliable for the identification or exclusion of LTBI once the CD4 cell count recovers to >= 100 cells/mm3.     

Syndemic effect of mental illness and substance use on viral suppression among recently-incarcerated,HIV-infected individuals in the CARE+ Corrections study

Few studies on HIV-related syndemics of co-occurring and mutually reinforcing psychosocial conditions have assessed clinical outcomes in criminal justice (CJ)-involved populations. Baseline data from the CARE+ Corrections study were used to quantify co-occurring mental illness and substance use and examine syndemic effects on viral suppression among 106 CJ-involved HIV-infected individuals. Ninety-one (86%) reported a mental illness diagnosis, 30 (28%) reported hazardous alcohol use, and 61 (58%) were drug dependent. Eighteen (17%) experienced all three conditions. Drug dependence was clustered with mental illness (prevalence odds ratio [POR] 3.20, 95% CI 1.01–10.14) and hazardous alcohol use (POR 2.61, 95% CI 1.03–6.56). The association between syndemic score, representing the number of conditions reported by each individual, and viral suppression was not statistically significant, although 86% of participants with none of these conditions were virally suppressed, compared to 56% of those with all three (p?=?0.56). Mental illness and substance use were concentrated in this sample, indicating a need for integrated care services.     

Uptake and adherence to highly active antiretroviral therapy among HIV-infected people with alcohol and other substance use problems: the impact of substance abuse treatment

Aim We examined the association of substance abuse treatment with uptake, adherence and virological response to highly active antiretroviral therapy (HAART) among HIV‐infected people with a history of alcohol problems. Design Prospective cohort study. Methods A standardized questionnaire was administered to 349 HIV‐infected participants with a history of alcohol problems regarding demographics, substance use, use of substance abuse treatment and uptake of and adherence to HAART. These subjects were followed every 6 months for up to seven occasions. We defined substance abuse treatment services as any of the following in the past 6 months: 12 weeks in a half‐way house or residential facility; 12 visits to a substance abuse counselor or mental health professional; or participation in any methadone maintenance program. Our outcome variables were uptake of antiretroviral therapy, 30‐day self‐reported adherence and HIV viral load suppression. Findings At baseline, 59% (205/349) of subjects were receiving HAART. Engagement in substance abuse treatment was independently associated with receiving antiretroviral therapy (adjusted OR; 95% CI: 1.70; 1.03–2.83). Substance abuse treatment was not associated with 30‐day adherence or HIV viral load suppression. More depressive symptoms (0.48; 0.32–0.78) and use of drugs or alcohol in the previous 30 days (0.17; 0.11–0.28) were associated with worse 30‐day adherence. HIV viral load suppression was positively associated with higher doses of antiretroviral medication (1.29; 1.15–1.45) and older age (1.04; 1.00–1.07) and negatively associated with use of drugs or alcohol in the previous 30 days (0.51; 0.33–0.78). Conclusion Substance abuse treatment was associated with receipt of HAART; however, it was not associated with adherence or HIV viral load suppression. Substance abuse treatment programs may provide an opportunity for HIV‐infected people with alcohol or drug problems to openly address issues of HIV care including enhancing adherence to HAART.     

Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy

OBJECTIVE: To characterize the temporal changes in mortality and life expectancy among HIV-positive individuals initiating antiretroviral therapy in British Columbia, Canada, from 1993 to 2004. METHODS: This analysis was restricted to 2238 antiretroviral-naive HIV-positive individuals who started antiretroviral therapy between January 1993 and September 2004. The primary analysis endpoint was all-cause mortality stratified by four time periods: 1993-1995, 1996-1998, 1999-2001, and 2002-2004. Cox proportional hazard models, with associated 95% confidence intervals (CI), were used to estimate the hazard of death. Abridged life tables were constructed to compare life expectancies at the age of 20 years. RESULTS: Product limit estimates of the cumulative mortality rate at 12 months after therapy initiation decreased from 15.8% (+/- 1.6%) in 1993-1995 to 6.1% (+/- 1.1%) in 2002-2004. Life expectancy at the age of 20 years has increased from 9.1 years (+/- 2.3 years) in 1993-1995 to 23.6 years (+/- 4.4 years) in 2002-2004. Subjects in 1993-1995 were more likely to die than those who started therapy in 2002-2004 (hazard ratio 2.78; 95% CI 1.92-3.85). Patients who initiated dual therapy or therapies containing three or more antiretroviral drugs were, respectively, 1.49 (95% CI 1.23-1.82) and 2.56 (95% CI 2.13-3.13) times less likely to die than those who started on monotherapy. CONCLUSION: A significant and progressive decrease in mortality and increase in life expectancy were observed over the 12-year study period. The increase in life expectancy and decrease in mortality were directly associated with the use of modern forms of HAART.     

Alternative therapy use in HIV-infected patients receiving highly active antiretroviral therapy

The extent of use of alternative therapies, psychosocial and disease-specific variables predictive of alternative therapy use, and factors motivating the use of alternative therapies in HIV-infected patients receiving highly active antiretroviral therapy (HAART) have not been well defined. Types of alternative therapies used, demographic and medical data, coping (Billing and Moos inventory of coping with illness styles), social support (Irwing and Sarason questionnaire), sense of personal control (Pearlin's Mastery scale), quality of life (Medical Outcome Study scale), health beliefs, and adherence rate were prospectively assessed in 118 HIV-infected patients receiving HAART. Of 38% (45/118) of the patients who used alternative therapies, 56% (25/45) began using alternative therapies since the initiation of HAART. While Caucasian patients were more likely to use alternative therapies than all other patients (P = 0.015), new users of alternative therapies were more likely to be African-American (P = 0.022). Alternative therapy users reported less satisfaction with their emotional support (P = 0.027), and had greater psychological distress (P = 0.048), but were more likely to utilize problem-focused coping (P = 0.015). Patients who used alternative therapies were less likely to believe that HAART was beneficial (P = 0.06). Physicians were unaware of patients' alternative therapy use in 40% (18/45) of all patients who used alternative therapies, in 67% of herbal therapy users, and in 100% of dietary supplement users. Adherence to antiretroviral therapy, CD4 count, and HIV-RNA level were neither predictive nor affected by alternative therapy use. Despite scepticism about the benefits of HAART, resort to alternative therapies did not undermine adherence with antiretroviral therapy. Although able actively to cope with their illness, users of alternative therapies had greater psychological distress and were less satisfied with their emotional support. Interventions aimed at promoting their psychological well-being and enhancing the emotional support should be considered in these patients.     

Longitudinal changes in serum lipids among HIV-infected men on highly active antiretroviral therapy

OBJECTIVE: The aim of the study was to describe longitudinal changes in serum lipids among HIV-infected men receiving highly active antiretroviral therapy (HAART) with long-term follow-up. METHODS: A total of 304 HIV-infected men who initiated HAART and who had serum lipid measurements prior to and for up to 7 years after HAART initiation were identified from the Multicenter AIDS Cohort Study (MACS). Mean levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were examined at biannual time-points. RESULTS: Significant lipid changes were seen within 0.5 years of HAART initiation but increases in TC (+1.09 mmol/L), LDL-C (+0.57 mmol/L), HDL-C (+0.16 mmol/L) and non-HDL-C (+0.91 mmol/L) reached peak levels 2-3 years after HAART initiation. Declines in serum TC, LDL-C and non-HDL-C in subsequent years occurred concurrently with a substantial increase in use of lipid-lowering medications (from 1% usage pre-HAART to 43% 6-7 years after HAART initiation) but the proportion of men who either were treated with cholesterol-lowering medication or had elevated cholesterol levels (>5.18 mmol/L) did not change during the 2-7-year interval after HAART. Mean HDL-C also decreased after 2-3 years and was low (<1.04 mmol/L) in 55% of HIV-infected men 6-7 years after HAART initiation. CONCLUSIONS: Atherogenic serum lipids increased early after the initiation of HAART, peaked at 2-3 years and remained high or required treatment thereafter. Low HDL-C levels persisted in the majority of men. The long-term effects of lipid abnormalities on cardiovascular risk and the effectiveness and toxicity of prolonged use of lipid-lowering medications in combination with HAART are not known.     

Time to initiating highly active antiretroviral therapy among HIV-infected injection drug users

OBJECTIVE: Studies have shown that HIV-infected injection drug users (IDUs) are less likely to receive antiretroviral therapy than non-drug users. We assess factors associated with initiating highly active antiretroviral therapy (HAART) in HIV-infected IDUs. METHODS: A cohort study of IDUs carried out between 1 January 1996 and 30 June 1999 at a community-based study clinic affiliated to the Johns Hopkins University, Baltimore, Maryland. The participants were a total of 528 HIV-infected IDUs eligible for HAART based on CD4+ cell count. The main outcome measure was the time from treatment eligibility to first self-reported HAART use, as defined by the International AIDS Society-USA panel (IAS-USA) guidelines. RESULTS: By 30 June 1999, 58.5% of participants had initiated HAART, most of whom switched from mono- or dual-combination therapy to a HAART regimen. Nearly one-third of treatment-eligible IDUs never received antiretroviral therapy. Cox proportional hazards regression showed that initiating HAART was independently associated with not injecting drugs, methadone treatment among men, having health insurance and a regular source of care, lower CD4+ cell count and a history of antiretroviral therapy. CONCLUSIONS: Self-reported initiation of HAART is steadily increasing among IDUs who are eligible for treatment; however, a large proportion continues to use non-HAART regimens and many remain treatment-naive. Although both groups appear to have lower health care access and utilization, IDUs without a history of antiretroviral therapy use would have more treatment options available to them once they become engaged in HIV care.     

Review: thromboses among HIV-infected patients during the highly active antiretroviral therapy era

Venous thrombotic events (VTEs) may occur at higher rates among patients with HIV; some studies suggest that highly active antiretroviral therapy (HAART) may increase the risk for these potentially life-threatening events. We performed a retrospective study among patients with HIV to evaluate the incidence and risk factors for VTEs during the HAART era. A literature review was performed examining VTEs in the pre- and post-HAART eras. Seventeen (3.7%) of 465 patients with HIV experienced a VTE. The overall incidence rate of deep VTEs among HIV-positive persons was 377 cases per 100,000 person-years, a fourfold higher rate compared to age-matched males in the general population. The median age at VTE was 36 years (range, 27-68). Patients with a thrombosis compared to those without had significantly lower current CD4 (153 versus 520 cells/mm(3), p < 0.001) and nadir (76 versus 276 cells/mm(3), p < 0.001) CD4 counts, higher viral loads (3.6 versus 1.7 log(10) copies per milliliter, p = 0.003), and more likely to have a diagnosis of AIDS (76% versus 32%, p < 0.001); there were no differences in demographics, hyperlipidemia, current use of HAART, the duration of HAART or protease inhibitor (PI) exposure. A review of the literature noted 129 VTE cases; mean age was 40 years, mean CD4 count was 181 cells/mm(3), the majority of patients were not receiving HAART, and the most common risk factor was an ongoing infection. Thrombotic events are occurring among patients with HIV despite their relatively young ages. Advanced HIV disease is a risk factor for development of thromboses, possibly due to an increased inflammatory state or the presence of concurrent comorbidities such as infections. HAART or PI therapy does not appear to play a significant role in the occurrence of VTEs.     

The effect of highly active antiretroviral therapy on cervical cytologic changes associated with oncogenic HPV among HIV-infected women.

OBJECTIVE: Cervical intraepithelial neoplasia (CIN), a common condition among HIV-infected women, has been linked to HIV load and immune status. Highly active antiretroviral therapy (HAART) improves immunologic and virologic status. This study was undertaken to determine the relationship between HAART use and CIN. DESIGN: Cohort study. The Women's Interagency HIV Study (WIHS) in five cities in the USA (Bronx/Manhattan, New York; Brooklyn, New York; Chicago, Illinois; Los Angeles, California; San Francisco Bay area, California; Washington, District of Columbia). METHODS: HIV-infected women were followed every 6 months with Papanicolaou smears and cervicovaginal lavage for human papillomavirus (HPV) DNA testing. To characterize exposures that changed over time and to capture the dynamic nature of cytologic changes, Papanicolaou smear findings from each participant's consecutive visits were defined as a pair. We determined the proportion of all pairs that exhibited either regression or progression, according to HAART exposure, HPV results and Papanicolaou smear status. As participants could contribute multiple pairs, inferences were based on robust methods to adjust for correlated observations. RESULTS: Women with persistent HPV infection were more likely to have progression of their lesions. After adjustment for CD4 cell count and Papanicolaou smear status, women on HAART were 40% (95% confidence interval, 4-81%) more likely to demonstrate regression and less likely (odds ratio, 0.68; 95% confidence interval, 0.52-0.88) to demonstrate progression CONCLUSIONS: HAART altered the course of HPV disease in HIV-infected women, reducing progression and increasing regression. As HPV disease is a common sex-specific manifestation of HIV disease this effect of HAART would be a major additional benefit from this modality of therapy.     

Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia

BACKGROUND: HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients. METHODS: Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively. RESULTS: From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6-78) cells/microl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51-100, 21-50 and < or = 20 cells/microl, respectively; P < 10). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained < or = 200 and < or = 100 cells/microl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/microl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05-0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52-0.98). Similar efficacy was found between the stavudine-lamivudine-nevirapine fixed dose combination and the combination stavudine-lamivudine-efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index. CONCLUSION: Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/microl, patients with CD4 cell count < or = 20 cells/microl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression.     

Setting a minimum threshold CD4 count for initiation of highly active antiretroviral therapy in HIV-infected patients

The aim of our study was to determine a minimum threshold CD4 count for highly active antiretroviral therapy (HAART) initiation in HIV-infected patients. A schema using longitudinal data from a clinical cohort was designed. The presenting CD4 counts of asymptomatic HIV-infected patients in Hong Kong were evaluated in relation to their progression to AIDS within 1 year of diagnosis of HIV infection. A graph was generated to depict the changes in the percentage of cumulative AIDS diagnoses for every 10 cell/microL increase in presenting CD4 count. Of 181 patients, 24 had developed AIDS within 1 year of diagnosis of HIV infection. Setting the CD4 count threshold at 150 cells/microL gave a good balance between the number of preventable AIDS-defining events and the number of non-AIDS patients initiating HAART. No extra AIDS-defining events occurred when the CD4 count threshold was reduced from 200 to 150 cells/microL, despite the addition of 13 more patients. In multivariate Cox regression analysis, presenting CD4 count was a significant predictor for AIDS occurrence. The relative hazard for AIDS occurrence of patients with presenting CD4 counts 相似文献   

Hospitalization risk following initiation of highly active antiretroviral therapy

Objectives

While highly active antiretroviral therapy (HAART) decreases long‐term morbidity and mortality, its short‐term effect on hospitalization rates is unknown. The primary objective of this study was to determine hospitalization rates over time in the year after HAART initiation for virological responders and nonresponders.

Methods

Hospitalizations among 1327 HAART‐naïve subjects in an urban HIV clinic in 1997–2007 were examined before and after HAART initiation. Hospitalization rates were stratified by virological responders (≥1 log₁₀ decrease in HIV‐1 RNA within 6 months after HAART initiation) and nonresponders. Causes were determined through International Classification of Diseases, 9th Revision (ICD‐9) codes and chart review. Multivariate negative binomial regression was used to assess factors associated with hospitalization.

Results

During the first 45 days after HAART initiation, the hospitalization rate of responders was similar to their pre‐HAART baseline rate [75.1 vs. 78.8/100 person‐years (PY)] and to the hospitalization rate of nonresponders during the first 45 days (79.4/100 PY). The hospitalization rate of responders fell significantly between 45 and 90 days after HAART initiation and reached a plateau at approximately 45/100 PY from 91 to 365 days after HAART initiation. Significant decreases were seen in hospitalizations for opportunistic and nonopportunistic infections.

Conclusions

The first substantial clinical benefit from HAART may be realized by 90 days after HAART initiation; providers should keep close vigilance at least until this time.

     

Immune restoration disease in HIV-infected individuals receiving highly active antiretroviral therapy: clinical and immunological characteristics

BACKGROUND: HIV-infected patients responding to HAART can show a diverse spectrum of symptoms caused by inflammatory reaction. The pathogenesis of this phenomenon, called immune restoration disease (IRD), is unclear. This study describes the spectrum of IRD and analyses the immunological and clinical parameters that could be related to its development. METHODS: In a retrospective, matched case-control study, 17 HIV-infected individuals who developed inflammatory symptoms < 12 months after initiation of HAART were included. HIV-infected controls were matched for age, gender and CDC classification. Factors included in the analysis were: CD4+ and CD8+ cell counts, deltaCD4+ and deltaCD8+, CD4/CD8 ratios, HIV-1-RNA load (VL), AVL and the number of CDC events prior to HAART. RESULTS: The median time after initiation of HAART and developing IRD (n = 17) was 72 days (range 2-319). In nine cases (53%) a mycobacterial infection was identified as the underlying cause. HAART was started at a mean CD4+ count (+/- SD) of 55 x 10(6) /l (+/- 59) and 85 x 10(6) /l (+/- 78.0) for cases and controls, respectively (p = 0.13). After initiation of HAART, the CD4+ count showed a 10.6 fold increase at the onset of IRD in the cases and a 2.7 fold increase in the controls in an equal period of time (p = 0.020). The other parameters analysed did not differ significantly between cases and controls. CONCLUSION: We conclude that the risk of developing IRD is associated with a high-fold increase in CD4+ lymphocytes. In this study, mycobacteria are the pathogens most frequently associated with IRD.     

Nutritional aspects of HIV-infected children receiving highly active antiretroviral therapy

The presentation of the nutritional problems of HIV-infected children is changing over time with improved antiretroviral regimens. Early reports of HIV infection in the 1980s, included such problems as malnutrition and wasting. However, as treatment and prophylactic regimens improve, the current nutritional problems of HIV-infected children in developed countries include truncal obesity and insulin resistance in addition to malnutrition. Background data on the wasting syndrome, etiology of malnutrition, nutritional effects of highly active antiretroviral therapies, and nutritional intervention strategies for HIV-infected children will be presented.     

Improving health outcomes among individuals with HIV, mental illness, and substance use disorders in the Southeast

Providing behavioral treatment for mental health and substance use disorders among HIV-infected individuals is critical because these disorders have been associated with negative outcomes such as poorer medication adherence. This study examines the effectiveness of an integrated treatment model for HIV-infected individuals who have both substance use and mental disorders. Study participants (n = 141) were recruited through routine mental health and substance abuse screening at tertiary Infectious Disease clinics in North Carolina. The study participants received integrated mental health and substance abuse treatment for one year and were interviewed at three-month intervals. Using linear regression analyses, we detected statistically significant decreases in participants' psychiatric symptomatology, illicit substance use, alcohol use, and inpatient hospital days. Participants also reported fewer emergency room visits and were more likely to be receiving antiretroviral medications and adequate psychotropic medication regimens at follow-up. No changes in sexual risk, physical health, or medical adherence were detected after treatment participation. This integrated treatment model offers an option for treating HIV-infected individuals with mental health and substance use disorders that can be adapted for use in a variety of psychiatric and medical treatment settings.