Hospitalization rates in an urban cohort after the introduction of highly active antiretroviral therapy

OBJECTIVE: Previous studies have shown a decrease in hospitalization rates associated with the introduction of highly active antiretroviral therapy (HAART). To evaluate hospitalization rates and patterns in discharge diagnoses that changed between 1995 and 1998 and to examine risk factors for hospitalization in HIV-positive patients, we conducted a cohort study. PATIENTS AND METHODS: All inpatient hospitalizations of 2,151 HIV-positive patients enrolled in our university-based HIV clinic between January 1, 1994 and December 31, 1998 with a CD4 count within a 6-month calendar semester were examined to evaluate hospitalization rates, discharge diagnoses, and intensive care department use. Negative binomial regression was used to assess the effect of various risk factors on hospitalization. RESULTS: Hospitalization rates decreased between 1995 and 1996 but increased between 1997 and 1998. In multivariate regression, female gender (incidence rate ratio [IRR], 1.45; p <.001), injection drug use (IRR, 1.36; p <.001), and having received no antiretroviral therapy were strong predictors of total hospitalization. White race, low CD4 count, and no antiretroviral treatment were strong predictors of hospitalization for an opportunistic infection. Female gender (IRR, 1.45; p <.001), African-American ethnicity (IRR, 1.22, p =.05), no antiretroviral treatment, and low CD4 counts were predictive of higher hospitalization rates for nonopportunistic infection-related diagnoses. Intensive care department-use was associated with white ethnicity (IRR, 1.86; p =.028), heterosexual transmission of HIV (IRR, 1.90; p =.009), no antiretroviral treatment, and low CD4 count at enrollment. CONCLUSIONS: Our data indicate that hospitalization rates decreased between 1995 and 1997 after introduction of HAART, but that they then increased between 1997 and 1998, particularly for diagnosed nonopportunistic infections. If these trends continue, it indicates that patients may be developing previously unseen comorbidities and that HAART may have reached or exceeded a threshold in its effectiveness in reducing the clinical morbidity that results in hospital admission.     

Factors and temporal trends associated with highly active antiretroviral therapy discontinuation in the Women's Interagency HIV Study

We characterized factors and temporal trends associated with discontinuation of highly active antiretroviral therapy (HAART) among 936 HIV-infected women enrolled in the Women's Interagency HIV Study. A multivariate analysis of post-HAART initiation exposures found that high HIV RNA levels (relative hazard [RH] = 1.36, P < 0.001) and high depressive symptom scores (RH = 1.53, P = 0.012) were associated with HAART discontinuation. The adjusted hazard of discontinuation was higher in the 2 most recent calendar periods compared with the first (RH = 1.61, P = 0.026; RH = 1.56, P = 0.074, respectively). The increasing risk of HAART discontinuation in recent calendar periods and changes in the clinical factors associated with discontinuation reflect ongoing and dynamic shifts in the approach to HAART utilization.     

Interruption of highly active antiretroviral therapy in HIV clinical practice: results from the Italian Cohort of Antiretroviral-Naive Patients

OBJECTIVES: To investigate the frequency of a first therapy interruption (TI) > or = 12 weeks, to identify the factors associated with TI and with therapy resumption, and to compare the risk of developing clinical events during TI and during continuous therapy. METHODS: Observational study of 3142 patients who started a first highly active antiretroviral therapy (HAART) regimen. End points were time to (1) first TI of > or = 12 weeks, (2) subsequent therapy resumption, and (3) development of new AIDS-related events or death. RESULTS: Over a median follow-up period of 41 months (interquartile range: 18-60 months), 721 patients (22.9%) interrupted HAART for > or = 12 weeks, with a probability of 28.6% (95% confidence interval [CI]: 26.7-30.6) by 4 years from the date of therapy initiation. Patient decision (47.4%) and toxicity (24.0%) were the main reasons for TI. Women, injection drug users, and patients with a higher current CD4 cell count were more likely to interrupt. The median time to therapy resumption was 12 months (95% CI: 11-14). The higher the current CD4 count, the slower was the rate of resuming therapy; conversely, patients who stopped because of failure and those with a pre-HAART viral load >100,000 copies/mL resumed therapy sooner. Two hundred eighty-one patients experienced clinical progression at a rate of 2.6 per 100 person-years (pys) (95% CI: 2.3-3.0) while patients were on therapy and 3.5 per 100 pys (95% CI: 2.4-4.8) during TI. The adjusted relative hazard of clinical progression associated with TI was 2.75 (95% CI: 1.14-6.65; P = 0.03). CONCLUSIONS: TI occurring in clinical practice is associated with an increased risk of clinical progression; hence, it should be discouraged outside strictly experimental settings.     

Effects of highly active antiretroviral therapy and its adherence on herpes zoster incidence: a longitudinal cohort study

Background

Herpes zoster (HZ) is common among HIV-infected individuals, but the impacts of highly active antiretroviral therapy (HAART) and HAART adherence on HZ risk have not been well studied.

Methods

The effects of HAART and HAART adherence on HZ incidence were evaluated by comparing HIV-infected women on HAART (HAART use group) with the HIV-infected women remaining HAART naïve (HAART naïve group) in the Women’s Interagency HIV Study (WIHS). A 1:1 matching with propensity score for predicting HAART initiation was conducted to balance background covariates at index visit, including HIV disease stage. Kaplan-Meier method was used to compare the risk of HZ development between the matched pairs. Cox proportional hazard models were used to assess the effects of HAART and HAART adherence on HZ incidence.

Results

Through propensity score matching, 389 pairs of participants were identified and they contributed 3,909 person years after matching. The background covariates were similar between the matched pairs at the index visit. The participants had a mean age around 39 years old, and about 61% of them were Black and 22% were Latina. No significant difference in HZ risk was observed between the HAART use group and the HAART naïve group during the first year of follow-up in any analyses. In the univariate analysis, the HAART use group had marginally lower HZ risk (Hazard Ratio (HR): 0.72; 95% Confidence Interval (CI): 0.48-1.1) over the entire follow-up period. However, women with a HAART adherence level of ≥95% had significantly lower HZ risk (HR: 0.54; 95% CI: 0.31, 0.94) compared to the HAART naïve women. The association remained significant after adjusting for quality of life score and acyclovir use, but it attenuated and was no longer statistically significant after adjusting for an intermediate variable, either CD4+ T cell counts or HIV viral load.

Conclusions

Among adult women, we observed a significant preventive effect of long-term HAART use on HZ incidence when a HAART adherence level of ≥95% was attained, and this effect was mediated through reduction of HIV viral load and improvement of CD4+ T cell counts.

     

Sexual dysfunction in the highly active antiretroviral therapy era

The possible relationship between HAART and the development of sexual disturbances of HIV-infected patients remains yet unresolved because of the inconsistency of the results of the different studies. To analyze the current knowledge on this topic, MEDLINE files were searched for articles dealing with any manifestation of sexual dysfunction in the HAART era. Selected references from these articles as well as communications to the main HIV meetings were also reviewed. Sexual dysfunction seems to be a very common event after the introduction of HAART. The average prevalences of sexual dysfunction among the different studies was 51%, erectile dysfunction 46%, decreased libido 44%, ejaculatory disturbances 39% and orgasmic disorders 27%. These disturbances seemed to be more common in patients treated with protease inhibitors. Several relevant questions related to sexual dysfunction in these patients are addressed in this review, including the possible pathogenic mechanisms involved. Despite the inconsistent results among the studies, the data that support a direct or indirect role of HAART in the generation of these disturbances seem to exceed the data that do not support it. As a conclusion, antiretroviral therapy, particularly protease inhibitors, seems to be to some extent directly or indirectly related to sexual dysfunction through different mechanisms.     

Treatment-related factors and highly active antiretroviral therapy adherence

Adherence to highly active antiretroviral therapy (HAART) plays a critical role in the effectiveness of HIV treatment. Nevertheless, the complexity of regimens and frequent side effects make HAART extraordinarily difficult to take, and many HIV-infected persons fail to adhere. The current study offers an overview of the relationship between adherence and antiretroviral treatment-related variables. As for other chronic diseases, medication regimen complexity also has an impact on adherence in the management of HIV infection. In particular, the authors discuss the effect of pill burden, dosing frequency, dietary instructions, number and type of different medications prescribed, short- and long-term side effects, convenience, and ability to incorporate the treatment regimen into a daily routine. Medication side effects are common in HAART-treated persons and are associated with concurrent and future nonadherence. Simplification of regimens, adjustment of the drug schedule to the patient's specific lifestyle, and anticipation and self-management of side effects are treatment-based strategies to optimize HAART adherence and ensure the most effective, convenient, safe, and well-tolerated antiretroviral treatment.     

高效抗病毒治疗促使艾滋病患者免疫功能重建

艾滋病的特征是ＨＩＶ 1感染人体后 ,造成ＣＤ4 +Ｔ淋巴细胞数量进行性减少、细胞免疫功能损害 ,最后导致艾滋病 (ＡＩＤＳ)。先前的研究表明这种免疫功能的丧失是不可逆转的 ,抗ＨＩＶ病毒治疗仅能控制或减缓其进展。近年来 ,由于强效联合抗病毒治疗 (ＨＡＡＲＴ)的应用 ,艾滋病的发病率和死亡率均较前明显下降 (指西方国家 )。说明ＨＡＡＲＴ不仅能有效的控制ＨＩＶ 1的复制 ,并能使艾滋病病人的免疫功能得到恢复。这种ＨＡＡＲＴ使艾滋病病人免疫功能重建的假说最近被一组法国研究人员证实 ,艾滋病的免疫重建规律是 :(1)治疗早期ＣＤ4 +…     

Cytomegalovirus retinitis in the era of highly active antiretroviral therapy

Cytomegalovirus (CMV) is a common opportunistic infection in individuals with AIDS. Moreover, CMV retinitis represents a significant portion of end-organ disease in patients with CMV and AIDS. Prior to the advent of highly active antiretroviral therapy (HAART), almost one-third of people with AIDS developed CMV retinitis during their lifetime. Although effective therapies for CMV infection had been developed, treatment was often life-long due to persistent immune deficiency. Despite chronic suppressive maintenance therapy, disease relapse was nearly universal, and development of drug resistance was not uncommon. Widespread use of HAART has reduced the incidence and complications of CMV retinitis. With sustained immune recovery, discontinuation of anti-CMV therapy has been possible in many patients. Still, immune recovery does not guarantee protection from recurrent disease. CMV retinitis and uveitis associated with immune recovery remain causes of vision loss in this population and demand vigilance on the part of physicians.     

Gender and clinical outcomes after starting highly active antiretroviral treatment: a cohort study

OBJECTIVE: To examine gender differences in clinical response to highly active antiretroviral treatment (HAART). METHODS: A cohort of HIV-positive individuals was examined. Outcomes assessed were hospital admission and disease progression (either a new AIDS diagnosis or death) after starting HAART. Hazard ratios (HRs) derived using Cox regression methods compared female-to-male rates, adjusting for other factors independently associated with outcome. RESULTS: Four hundred ninety-seven men and 146 women were followed up over a median of 13 months after starting HAART. Eighty-one percent of men were white, and 75% were homosexual. Fifty-eight percent of women were black African, and 86% were in the heterosexual risk category. The baseline CD4 count was higher in men than in women (191 vs. 145 x 10; p < .01), but viral loads were similar (5.2 vs. 5.1 log copies/ml, respectively; p = .13). Fifty-six percent of men and women were treatment na?ve. Eighteen percent of men and women were admitted during follow-up, with 17% of male admissions and 12% of female admissions being the result of an AIDS-defining illness. The HR for admission was 0.76 (95% confidence interval [CI]: 0.46-1.27; p = .30) for women relative to men. Eleven percent of the men and 8% of the women experienced progression. Eighty-eight percent of progressions were the result of a new AIDS diagnosis (46 in men, 11 in women), and 8 men died. The HR for progression was 0.70 (CI: 0.36-1.33; p = .28). CONCLUSIONS: Our results suggest a possible benefit in women compared with men in the rate of outcomes after HAART. Further analysis with longer follow-up or greater numbers would enable a more powerful analysis to be performed.     

Survival in an urban HIV-1 clinic in the era of highly active antiretroviral therapy: a 5-year cohort study

OBJECTIVE: To examine the implications of early virologic response to highly active antiretroviral therapy (HAART) on long-term HAART utilization patterns, development of diabetes or hyperlipidemia, and mortality in an urban HIV-1 clinic. DESIGN: A cohort of 444 patients in an urban HIV-1 clinic, who started HAART prior to January 1, 1999, were categorized by virologic response in the first 18 months of therapy: durable viral suppression, initial suppression followed by rebound, and failure to achieve suppression. Antiretroviral exposure, HIV-1 RNA levels, CD4 cell counts, development of diabetes or hyperlipidemia, and survival were compared in the three groups. RESULTS: Over 4 years of follow-up, patients in the durable suppression group used HAART 82% of the time compared with 60% in the rebound group (p <.001) and 23% in the failure to suppress group (p <.001). Through 4 years of follow-up, patients in the rebound group had a cumulative exposure to a median of seven antiretroviral drugs (interquartile range [IQR]: 6-9) compared with five drugs in the durable suppression group (IQR: 4-6) and five drugs in the failure to suppress group (IQR: 3-7) (p <.001 for both comparisons with the rebound group). At 5 years, the estimated proportions surviving were 89% in the durable suppression group, 76% in the rebound group (p =.04), and 56% in the failure to suppress group (p <.001). During follow-up, 35% in the durable suppression group developed diabetes or hyperlipidemia compared with 24% in the rebound group (p =.15) and 8% in the failure to suppress group (p <.001). CONCLUSIONS: This study highlights the long-term implications of early virologic response to HAART for survival, accumulation of triple-class antiretroviral exposure, and development of HAART-associated toxicities.     

Clinical toxicity of highly active antiretroviral therapy in a home-based AIDS care program in rural Uganda

BACKGROUND: We evaluated clinical toxicity in HIV-infected persons receiving antiretroviral therapy (ART) in Uganda. METHODS: From May 2003 through December 2004, adults with a CD4 cell count < or =250 cells/microL or World Health Organization stage 3/4 HIV disease were prescribed ART. We calculated probabilities for time to toxicity and single-drug substitution as well as multivariate-adjusted hazard ratios for development of toxicity. RESULTS: ART (stavudine plus lamivudine with nevirapine [96%] or efavirenz [4%]) was prescribed for 1029 adults, contributing 11,268 person-months of observation. Toxicities developed in 543 instances in 411 (40%) patients (incidence rate = 4.47/100 person-months): 36% peripheral neuropathy (9% severe); 6% rash (2% severe); 2% hypersensitivity reaction; < or =0.5% acute hepatitis, anemia, acute pancreatitis, or lactic acidosis; and 13% other. Probabilities of remaining free from any toxicity at 6, 12, and 18 months were 0.76, 0.59, and 0.47 and from any severe toxicity at 6, 12, and 18 months were 0.92, 0.86, and 0.85, respectively. For 217 patients (21%), 222 single-drug substitutions were made, mostly because of peripheral neuropathy or rash. CONCLUSIONS: Clinical toxicities were common, but no patients discontinued ART because of toxicity. The most common toxicities, peripheral neuropathy and rash, were managed with single-drug substitutions. In resource-limited settings, toxicity from ART regimens containing stavudine or nevirapine is manageable but more tolerable regimens are needed.     

HAART对人类免疫缺陷病毒感染者淋巴细胞亚群的影响

应用流式细胞分析法通过分析检测41例AIDS患者与30例健康对照之间,以及21例AIDS患者在接受HAART治疗前后外周血淋巴细胞亚群的表达情况,研究感染HIV病毒以及HAART治疗对淋巴细胞亚群的影响。结果显示AIDS患者与健康对照相比,外周血CD4~+CD45RA~+、CD4~+CD28~+、CD4~+CD45RO~+、CD4~+CD95~+细胞比例明显低于正常对照,CD8~+CD95~+、CD8~+CD38~+、CD56~+细胞比例明显高于正常对照;经HAART治疗后,CD4~+CD45RA~+,CD4~+CD28~+细胞比例比治疗前升高,CD56~+细胞比例比治疗前显著下降。结果表明CD4~+T淋巴细胞表面CD45RA、CD28表达,以及CD56~+细胞能够预测AIDS患者HAART治疗效果。     

HIV/AIDS患者HAART后颈动脉内膜中层厚度的变化

目的 探讨HAART后HIV/AIDS患者颈总动脉分叉处内中膜厚度的变化并分析相关因素.方法 我们对40例初治患者和98例正在治疗的患者进行了横断面研究,根据患者的治疗时间将接受治疗的患者分为三组,通过多普勒超声检测颈总动脉分叉处内膜中层厚度、流式技术检测CD4+T细胞绝对计数,使用PCR检测血浆病毒载量,收集患者临床资料,如年龄、空腹血脂(包括总甘油三酯、总胆固醇、HDL、LDL)水平、D-二聚体检测值.使用SPSS 19.0对患者各项检查结果进行单因素方差分析.结果 四组患者性别年龄没有统计学差异,治疗前CD4+T细胞绝对计数之间的差异具有统计学意义(P＜0.05),且治疗越早的患者治疗前CD4+T细胞绝对计数越低.相比于未治疗的患者,治疗后患者的CD4+T细胞绝对计数、颈总动脉分叉处内膜中层厚度、胆固醇水平及HDL水平均升高,血浆病毒载量下降,且差异有统计学意义(P＜0.05).治疗后患者之间并无统计学差异.结论 HIV/AIDS患者HAART后颈动脉内中膜厚度增厚可能与血脂异常有关,而且可能发生在HAART的早期.     

Assessing the efficacy of highly active antiretroviral therapy in the brain

The devastating effects of HIV infection have been documented for the last 2 decades. Since the 1980s over 60 million people have been infected and at present 40 million people globally are living with HIV. HIV infects the central nervous system (CNS) early in the disease process. Indeed, numerous studies document the presence of HIV within the cerebrospinal fluid (CSF). Direct infection of the brain by HIV ultimately results in HIV associated dementia (HAD), which (prior to the advent of antiretroviral therapy) affected 20% of patients. An increasing number of drugs have been developed to treat this infection and delay the development of AIDS. Current treatment is aimed at inhibiting viral replication, and thus, lowering the viral load. However a subsequent increase in viral load can occur as patients become resistant to drug therapy. In the era of HAART, the incidence of HAD has been reduced, whereas the prevalence rate is increasing as people with HIV survive longer. However, in a study of initial AIDS defining illnesses, the proportion with HIV related dementia did not decline following introduction of HAART. In a separate study, no decrease was found in the incidence of dementia per se, although there was a decrease in the incidence of all AIDS-defining illnesses during this time period. It is evident from most studies that since the introduction of HAART, its effect on HAD is not entirely clear, although the majority of findings indicate that it is beneficial. Here we will outline the issues relevant to preventing HAD by HAART.