Hospitalized HIV-infected patients in the HAART era: a view from the inner city

To evaluate hospitalizations of HIV-infected patients in the highly active antiretroviral therapy (HAART) era, we analyzed 2736 admissions of 1562 HIV-infected patients to Cook County Hospital from September 20, 1999 to July 10, 2002. Patients were predominantly African American (81%), male (72%), and active substance abusers (74%). Only 48% of patients with a prior HIV diagnosis were taking HAART and 37% of them had a viral load less than 1000 copies per milliliter. Patients on protease inhibitor (PI)-sparing regimens more frequently achieved a viral load less than 1000 copies per milliliter than those on a PI-containing regimens (41% vs. 34% p = 0.036). For patients with CD4 cell counts less than 200 cells per milliliter, those not taking HAART were more likely African American (83% vs. 76%, p < 0.031), homeless (13% vs. 5%, p < 0.001), active substance abusers (79% vs. 65%, p < 0.001), female (28% vs. 22%, p = 0.001), new to the hospital system (19% vs. 6%, p < 0.001), or not recently seen in the outpatient clinic (42% vs. 17%, p < 0.001). In our population, active substance abuse was prevalent and only a minority of patients was taking HAART. Women were receiving HAART less often, independent of race and substance abuse. Aggressive programs are needed in high-risk populations to address substance abuse issues and to improve patient use of HAART.     

Retrospective analysis of suspending HAART in selected patients with controlled HIV replication

We sought to determine the consequences of stopping highly active antiretroviral therapy (HAART) in a group of 41 HIV-infected individuals with undetectable HIV viral loads and CD4+ counts greater than 500 cells per microliter for 6 months or more. Clinical and laboratory parameters were monitored, as was the time to HAART reinitiation. Three months after HAART interruption, the median CD4+ count declined by 162 cells per microliter and HIV viral load increased by 24,000 copies per milliliter. Over the next year, CD4+ counts continued to decrease by an average of 11 cells per microliter per 3-month intervals. In contrast, HIV viral loads remained stable over the same period. Five of 7 patients (71%) with elevated cholesterol levels and 6 of 13 patients (46%) with elevated triglyceride levels had these values normalize after stopping HAART. After a median of 21 months follow-up, 26 of 41 patients (63%) have restarted HAART. Patients with Centers for Disease Control (CDC) HIV/AIDS C classification were more likely to restart HAART than those with A or B classification (p = 0.008). Reasons for HAART restart included clinical events in 8 patients. Fifteen patients restarted HAART for immunologic reasons: CD4+ count less than 300 cells per microliter (n = 7); HIV viral load greater than 55,000 copies per milliliter (n = 3); or both (n = 5). Three patients restarted HAART because of personal preference. Within 4 months, all 26 patients who restarted HAART achieved HIV viral loads less than 50 copies per milliliter. Although patients were able to rapidly achieve nondetectable HIV viral loads after restarting HAART, the inability to foresee clinical events among 8 patients (20%) is disconcerting. We advise caution before HAART interruption, particularly for those patients with a preceding history of significant HIV-related complications.     

Oral candidosis as a clinical marker of immune failure in patients with HIV/AIDS on HAART

Oral candidosis (OC) has been proposed as a clinical marker of highly active antiretroviral therapy (HAART) success or failure. The principal objective of this work was to assess whether the presence OC is associated with immunologic or virologic failure in patients with HIV/AIDS undergoing HAART. One hundred fifty-one patients with HIV/AIDS from Regional Hospital "Carlos Haya," Malaga, Spain, were examined orally. All patients had been undergoing HAART for a minimum of 6 months prior to oral examination. OC diagnosis was in accordance with World Health Organization-Centers for Disease Control (WHO-CDC) criteria. Age, gender, route of HIV infection, CD4 lymphocyte counts, and viral load were taken from the medical records. In regard to HAART response the patients were classified as: virologic- responders (viral load < 50 copies per milliliter), virologic nonresponders (viral load >50 copies per milliliter); immunologic responders (CD4 cells counts > 500 per milliliter), and immunologic nonresponders (CD4 cells counts < 500 per milliliter). Prevalence of OC was determined for each group. The presence of OC was closely related to immune failure (p 0.006; odds ratio [OR] 3.38 95% confidence interval [CI] 1.262-12.046) in patients with HIV/AIDS undergoing HAART. The probability of immune failure in the presence of OC was 91% for men who have sex with men, 95.5% for heterosexuals, and 96% for intravenous drug users. In conclusion, OC should be considered a clinical marker of immune failure in patients with HIV/AIDS undergoing HAART.     

Development of opportunistic infections after diagnosis of active tuberculosis in HIV-infected patients

Despite advances in highly active antiretroviral therapy (HAART), its use during tuberculosis (TB) treatment is fraught with challenges, often leading to delayed therapy. This report describes the course of HIV infection and outcomes of 26 consecutive TB/HIV coinfected patients who received TB treatment in Rhode Island. HIV infection was diagnosed in 26 (4%) of 598 TB cases in during a 10-year period. Of these patients, TB was the first indication of HIV infection in 15 patients (58%). Of the 21 patients who were not on antiretrovirals at the time of TB diagnosis, 17 (81%) met criteria for immediate initiation of HAART. The median CD4 cell counts and HIV-1 plasma viral load were 80 cells per microliter (range, 2-800 cells per microliter) and 255,631 copies per milliliter (range, 50,000 to > 500,000 copies per milliliter), respectively, for the patients whose baseline measurements were available. CD4 lymphocyte count was less than 200 cells per microliter in 13 (76%) of the 17 patients whose measurements were available. Three (30%) of the 10 patients whose CD4 cell count was less than 100 cells per microliter developed subsequent AIDS-defining illness prior to the initiation of HAART and a fourth patient, within 30 days of starting HAART. None of the patients who had CD4 cell counts 100 cells per microliter or greater developed subsequent AIDS-defining illness during TB treatment. The median time to starting HAART after starting TB treatment was 12 weeks (range, 3-36 weeks). From our limited experience based on this case series, we recommend early initiation of HAART in coinfected patients with CD4 cell counts less than 100 cells per microliter.     

Highly active antiretroviral therapy as the sole treatment for AIDS-related primary central nervous system lymphoma: a case report with implications for treatment

A 40-year-old male presented to medical attention with Pneumocystis jiroveci pneumonia and HIV infection. His CD4+ count was 18 cells per microliter and his HIV viral load (VL) was more than 400,000 copies milliliter. After 3 weeks of antibiotic therapy, he continued to have global cognitive deficits. A brain imaging study showed a right temporal mass, which on biopsy proved to be primary central nervous system lymphoma (PCNSL). He began highly active antiretroviral therapy (HAART) but declined palliative whole-brain radiotherapy (WBRT). Four months later, his CD4+ count had improved to 153 cells per microliter and his HIV VL was less than 75 copies per milliliter. At 36 months follow-up, he remained in complete remission (CR). Through a literature review, we identified 4 additional PCNSL patients who achieved prolonged remission after the initiation of HAART. One patient required WBRT and ventriculo-peritoneal shunting for signs and symptoms of obstructive hydrocephalus. The other 3 patients presented with stable neurologic findings and were treated with HAART alone. The median initial CD4+ count for these patients was 50 cells per microliter (range, 2 to 220 cells per microliter). All 5 remained in CR with a median follow-up of 23.5 (range, 13 to 36) months. For patients who present with PCNSL as their initial AIDS-defining event, stable neurologic findings, and effective HAART options, initial treatment with HAART alone may be possible, reserving WBRT and corticosteroids for those who show signs of impending neurologic demise. Chemotherapy and other novel approaches could also be considered for selected patients with lesser degrees of immune suppression and high baseline functional status.     

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.     

The effect of a multidisciplinary program on HAART adherence

Although emerging evidence suggests differing interventions may improve antiretroviral adherence, there has not been a formal evaluation to identify the impact of a clinic-based multidisciplinary program designed to provide education and identify and correct potential adherence barriers prior to the initiation of highly active antiretroviral therapy (HAART). A retrospective cohort study utilizing a historical control group was conducted to compare duration on antiretrovirals, clinical indicators, and adherence rates, as captured by pharmacy refill records. Two hundred sixty-one patients met criteria for inclusion (109 subjects, 152 controls). Time to stopping antiretrovirals, as evidenced by Kaplan-Meier plot, was significantly higher in Protocol group than Controls (log-rank p = 0.023): the median duration on HAART for the intervention group was greater than 360 days but only 210 days for the control group. Thus, more subjects in the protocol group continued on therapy for the full year: 60 (55%) versus 65 (43%) for the control group. The mean reduction in log10 viral loads between HAART initiation and 12 months was greatest for the intervention group with viral load at HAART initiation 100,000 copies per milliliter or more, -3.57 versus -1.78 for controls with viral load less than 100,000 copies per milliliter (p < 0.001). For the intervention group, the mean number of adherence barriers identified per person was 4% and 72% were found to have three or more barriers. Patients at high risk for poor adherence benefit from multidisciplinary education and proactive identification of adherence barriers by exhibiting prolonged duration on therapy and greater reduction in log10 viral loads.     

300例艾滋病患者高效抗逆转录病毒治疗后免疫重建规律探讨

目的探讨高效抗逆转录病毒治疗（HAART）对中国南部地区艾滋病患者的免疫重建规律。方法收集近3年来300例患者的完整资料,按基线CD4^＋T细胞数分为A、B、C三组,观察基线及治疗1、3、6、12月末CD4^＋T淋巴细胞数、12月末血浆病毒载量（VL）、临床症状和毒副作用。结果抗病毒治疗12月末300例患者CD4^＋T淋巴细胞计数平均上升127个／1,以治疗3月后增长明显,3、12月末与基线CD4^＋T淋巴细胞计数比较差异有显著性（P〈0．05）;12月末273例（91％）患者血浆病毒载量（VL）〈5copies/ml,27例（9％）患者病毒载量（VL）〉50copies/ml,高病毒载量A组16例,C组4例;A组与C组比较差异有显著性（P〈0．05）;药物不良反应主要是外周神经炎（35．4％）、骨髓抑制（18．2％）、皮疹（15．2％）、肝功能损害（12．1％）、乳酸酸中毒（12．1％）和肾结石（6．1％）。结论HAART治疗对中国南部地区的艾滋病患者有效,能够实现免疫重建,但存在较多毒副作用。     

Recrudescent Kaposi's sarcoma after initiation of HAART: a manifestation of immune reconstitution syndrome

The objective of this case series and literature review is to characterize the clinical course and prognosis of HIV-infected patients with Kaposi's sarcoma (KS) flare during immune reconstitution inflammatory syndrome (IRIS), a heterogeneous and sometimes fatal disorder of immune perturbation after initiation of highly active antiretroviral therapy (HAART). Medical records of 9 HIV-infected patients with KS flare after virologic and immunologic response to HAART were reviewed from a single institution. An additional 10 cases were abstracted by computerized search of the medical literature. In our single institution series, mean time to onset of KS flare was 5 weeks. Pretreatment mean CD4+ count was 190 cells/mm(3) and mean HIV viral load was 153,934 copies per milliliter. During flare, mean CD4+ count was 256 cells/mm(3) and mean HIV viral load was 1156 copies per milliliter. Similar aggregate results are represented in the literature. Six fatalities are reported, 4 from pulmonary KS and 2 from unrelated causes. Systemic chemotherapy universally led to tumor regression, but was administered in only 10 of 19 cases. In no instance was HAART discontinued. Onset of IRIS-associated KS flare is observed as early as 3 weeks, with most cases diagnosed within 2 months after immunologic and virologic response to HAART. Such a flare does not necessarily portend a poor prognosis. Even for those patients with rapidly symptomatic KS, early systemic chemotherapy is effective in suppressing IRIS-associated flare. Close clinical supervision is warranted for the KS patient initiating, changing, or resuming HAART. Particular vigilance is recommended for pulmonary involvement.     

Low effectiveness of highly active antiretroviral therapy and high mortality in the Greenland HIV-infected population

Greenland is a high-income country with free access to human immunodeficiency virus (HIV) care, including highly active antiretroviral therapy (HAART). We aimed to examine the HIV prevalence, age and gender distribution, and the effectiveness of HAART on CD4 positive cell count, viral load (VL), and mortality in the Greenland HIV-infected population. In this population-based cohort study we collected demographic, clinical and biochemical data on all HIV-infected patients followed in health clinics since 1995. For each case, we identified 100 age- and gender-matched population controls. The HIV cohort included 103 patients of whom 91% were Inuit; 81% were infected heterosexually. Only 40% of the patients had a VL <400 copies/ml at 48 weeks after starting HAART, and patients on HAART had a substantial excess relative mortality compared with the general population (mortality rate ratio [MRR]: 10.6; 95% confidence interval [CI]: 6.9-16.4). After the introduction of HAART, the mortality decreased (MRR: 2.5; 95% CI 0.9-6.8), but remained high with a mortality rate of 62 per 1000 person-years (py) (95% CI 29-129). Our findings underline the difficulties of implementing successful HIV treatment even with unlimited economic resources and free access to health care.     

Inpatient treatment of PCP abusers and users

Screening of 155 consecutive admissions to a voluntary, 4-6 week substance abuse inpatient rehabilitation program revealed a 13% prevalence of PCP abuse (defined by DSM-III criteria) and a 23% prevalence of nonabusive PCP use. The 20 PCP abusers were significantly younger (31.6 vs 40.2 years) and had more prior arrests (2.0 vs 0.8) than the 36 nonabusive users, but did not differ in other sociodemographic characteristics. The age range of patients was older than previously reported in the literature, with three PCP abusers (15%) and 15 users (42%) 40 years of age or older. A majority of both abusers (80%) and users (97%) also abused other drugs, including alcohol (57%), opiates (29%), marijuana (29%), and stimulants (18%). The mean length of stay for PCP abusers was 27 days, with 11 completing inpatient treatment. Urine samples were collected upon admission from all patients and assayed for PCP by gas chromatography with N-P detection (sensitivity = 0.1 ng/mL). Patients with initial positive PCP results had follow-up urines collected at least weekly until the PCP assay was negative or they left the treatment program. Twenty-seven percent of patients had PCP detected in admission urine samples, one-third of whom initially denied PCP use. Six patients still had PCP detected after 4 weeks of hospitalization, without evidence of PCP reuse. These findings suggest that PCP abuse and use are common among unselected patients seeking substance abuse inpatient treatment and that they are not confined to the adolescent/young adult age group.     

Rate of HIV-1 RNA rebound upon stopping antiretroviral therapy.

OBJECTIVE: To determine the rate of plasma HIV-1 RNA rebound in patients stopping highly active antiretroviral therapy (HAART) after achieving undetectable viral load. DESIGN: Sequential plasma HIV RNA levels were measured in six patients during the 21 days following withdrawal from HAART. METHODS: Plasma samples were obtained from six patients who chose to withdraw from HAART because of lipodystrophy, narcotic overdose, insomnia and/or high blood pressure. Longitudinal plasma viral load was determined in triplicate upon stopping therapy. RESULTS: All patients had plasma viral loads below 50 HIV RNA copies/ml at the time of stopping therapy and had had levels below 500 copies/ml for a median of 390 days (range 39-542 days). Plasma HIV rebound upon stopping therapy was rapid (median increase 0.2 log/day; range 0.15-0.42 log/day) and initially appeared to follow first-order kinetics. Plasma HIV RNA levels returned to greater than 500 copies/ml within 6 to 15 days (median 10 days) and approached or exceeded pre-therapy levels in all patients within 21 days of stopping therapy. Extrapolating backwards to the time at which individuals stopped therapy suggested that patients had tens of thousands of total body plasma HIV RNA copies despite having 'undetectable' plasma HIV RNA. CONCLUSIONS: HIV RNA in plasma rebounds within days of stopping antiretroviral therapy. A considerable burden of total body plasma HIV RNA likely remains even during effective HAART therapy.     

Challenges of antiretroviral treatment in transient and drug-using populations: the SUN study

This is an open-label, single-arm, phase 3b study (part of phase 3 development) to evaluate the efficacy and safety of Fortovase-soft gelatin formulation (saquinavir-SGC), combined with zidovudine (ZDV) and lamivudine (3TC), human immune deficiency virus type 1 in (HIV-1)-positive, antiretroviral-naive individuals. Forty-two HIV-1-positive adults with plasma HIV RNA >10,000 copies per milliliter (Roche Amplicor HIV Monitor assay) and CD4 cell count >100 cells/mm(3) were treated with SQV-SGC, 1200 mg three times per day; ZDV, 300 mg; and 3TC, 150 mg each twice per day for 48 weeks. High proportions were drug users (26%), demonstrated psychiatric disorders (alcohol abuse [14%]/depression [14%]), or were inadequately housed (5%). At 48 weeks, 50% of patients achieved viral suppression <400 copies per milliliter with 43% <20 copies per milliliter using an intent-to-treat analysis (missing values counted as virological failures). Corresponding proportions for patients remaining on therapy at 48 weeks were 91% <400 copies per milliliter and 78% <20 copies per milliliter. Most adverse events were mild. Saquinavir-SGC combined with ZDV and 3TC, achieved potent and durable HIV RNA suppression and was well tolerated over 48 weeks in an antiretroviral-naive population including high proportions of individuals considered difficult to treat, such as drug users, people with psychiatric problems and homeless individuals.     

Advanced liver fibrosis in HIV/HCV-coinfected patients on antiretroviral therapy

HIV infection is believed to adversely affect the progression of hepatitis C virus (HCV)-related liver disease. However, information regarding HIV and HCV coinfection in the era of highly active antiretroviral therapy (HAART) is scarce. A cross-sectional study in 75 HCV/HIV-coinfected patients (most of them on HAART) and 75 HCV-monoinfected patients paired by age, sex, and date of liver biopsy analyzed the association of HIV infection with advanced liver fibrosis (Knodell fibrosis stages 3 + 4). The median CD4 cell count in HIV-coinfected patients was 546 cells/microl; 78.7% had an HIV-1 viral load <1000 copies/ml and 88% were on antiretroviral therapy. The percentage of patients harboring genotype 4 and with a higher HCV viral load was greater in the HIV-coinfected group. HCV/HIV-coinfected patients had more advanced liver fibrosis (Knodell fibrosis stages 3 + 4) than HCV-monoinfected patients (46.7% vs. 12%, p < 0.0001). In the univariate analysis, the factors associated with advanced liver disease were male sex (OR: 2.7, 95% CI: 1.05-7.1), history of injecting drug use (OR: 4.6, 95% CI: 2.0-10.2), HIV infection (OR: 6.4, 95% CI: 2.7-14.7), and previous exposure to therapy with protease inhibitors (OR: 3.0, 95% CI:1.4-6.3). In the multivariate analysis; only male sex (OR: 3.17, 95% CI: 1.152-8.773) and HIV infection (OR: 6.85, 95% CI: 2.93-16.005) were associated with advanced liver fibrosis. HIV infection is associated with advanced liver fibrosis. HIV/HCV-coinfected individuals on HAART are at risk of developing end-stage liver disease despite virological success and immunological reconstitution.     

Elevated resting energy expenditure among HIV-seropositive persons receiving highly active antiretroviral therapy.

OBJECTIVES: To ascertain the relationships between resting energy expenditure (REE), HIV RNA in plasma, and highly active antiretroviral therapy (HAART). DESIGN: Cross-sectional analysis using data of a large cohort study of nutrition in relation to HIV disease. METHODS: HIV RNA in plasma, REE, fat-free mass (FFM), and medication regimens were assessed at 530 visits among 372 participants in a cohort study of HIV-seropositive men and women. RESULTS: HIV RNA in plasma was directly correlated with REE. After adjustment for FFM, age, CD4 cell count and HAART use, there was an increase in REE of 90 kJ/day per log10 copies/ml increase in HIV RNA [95% confidence interval (CI) 16-164; P = 0.02). HAART use had an independent effect on REE. In patients reporting HAART use, adjusted REE was 339 kJ/day higher than in those not reporting HAART use (95% CI 177-501; P = 0.0001). CONCLUSIONS: Viral load and HAART appear to exert independent effects on REE. Although HAART may decrease metabolic rate by lowering viral burden, it appears to increase metabolic demands through some mechanism(s) independent of its effect on viral burden. This may result in elevated REE despite control of viral replication.     

Immune reconstitution syndrome in a patient with AIDS with paradoxically deteriorating brain tuberculoma

A 54-year-old man with an underlying AIDS experienced fever and lethargy. Magnetic resonance imaging (MRI) showed multiple small ring-enhancement lesions over pons, basal ganglion, thalami, and bilateral cerebral hemisphere. Because of the concurrent pulmonary tuberculosis (TB), presumptive diagnosis of tuberculous meningitis and brain tuberculoma was made. The patient's condition clinically improved after a 3-month anti-TB treatment coupled with highly active antiretroviral therapy (HAART), and his CD4-T lymphocyte count was increased from 17 cells/mm(3) (HIV viral load, 294,000 copies per milliliter) to 153 cells/mm(3) (HIV viral load, 5930 copies per milliliter). However, the follow-up MRI disclosed disappearance of some old brain lesions and development of some new ones; some previously identified tuberculoma became smaller in size, while some other enlarger. Of note, ring-enhanced brain lesions were found over the left frontal lobe and left posterior fossa with perifocal edema and hyperintensity in diffusion weighted MRI indicating abscess formation. Steroid was added based on the presumed paradoxical reaction of brain tuberculoma. Complete resolution of brain lesions was found on MRI 9 months later. Tuberculoma should be considered in a patient with AIDS with numerous intracranial lesions if TB involving other site(s) is definitively diagnosed, especially when the patient is receiving prophylactic trimethoprim-sulfamethoxazole and/or serologically negative for toxoplasmosis. Our report demonstrated the peculiar phenomenon of paradoxical reaction of brain tuberculoma during immune reconstitution and strengthens the belief that additional use of steroids for paradoxical reaction of brain tuberculoma is indicated after exclusion of other causes for the progressively enlarging brain lesions.