Effectiveness of highly active antiretroviral therapy among injection drug users with late-stage human immunodeficiency virus infection

Highly active antiretroviral therapy (HAART) has been shown to be effective in different populations, but data among injection drug users are limited. Human immunodeficiency virus-infected injection drug users recruited into the Acquired Immunodeficiency Syndrome Link to Intravenous Experiences (ALIVE) Study as early as 1988 were tested semiannually to identify their first CD4-positive T-lymphocyte cell count below 200/microl; they were followed for mortality through 2002. Visits were categorized into the pre-HAART (before mid-1996) and the HAART eras and further categorized by HAART use. Survival analysis with staggered entry was used to evaluate the effect of HAART on acquired immunodeficiency syndrome-related mortality, adjusting for other medications and demographic, clinical, and behavioral factors. Among 665 participants, 258 died during 2,402 person-years of follow-up. Compared with survival in the pre-HAART era, survival in the HAART era was shown by multivariate analysis to be improved for both those who did and did not receive HAART (relative hazards = 0.06 and 0.33, respectively; p < 0.001). Inferences were unchanged after restricting analyses to data starting with 1993 and considerations of lead-time bias and human immunodeficiency viral load. The annual CD4-positive T-lymphocyte cell decline was less in untreated HAART-era participants than in pre-HAART-era participants (-10/microl vs. -37/microl, respectively), suggesting that changing indications for treatment may have contributed to improved survival and that analyses restricted to the HAART era probably underestimate HAART effectiveness.     

河南省HIV-1感染者抗病毒治疗效果及耐药发生的研究

目的 了解河南省部分地区HIV-1感染者高效抗逆转录病毒治疗效果及耐药变异发生情况.方法 招募HIV-1感染者105例,每半年进行1次调查,利用流式细胞技术对CD4+T淋巴细胞计数,使用NASBA方法测定病毒载量,利用RT-PCR方法扩增HIV-1 pol区基因,进行基因型耐药性分析.结果 接受抗病毒治疗后HIV-1感...     

Limited effect of highly active antiretroviral therapy among HIV-positive injecting drug users on the population level

There is evidence that HIV-positive injecting drug users benefit less than other risk groups from highly active antiretroviral therapy that has been available since 1996. In this multicentre European study the impact of the availability of highly active antiretroviral therapy on the progression rates to AIDS and death among injecting drug users with a documented date of HIV seroconversion is studied. After highly active antiretroviral therapy became available the risk of AIDS and death for injecting drug users decreased by 28% and 36%, which is less than has been reported for other risk groups.     

When to initiate highly active antiretroviral therapy: a cohort approach

The appropriate immunologic stage of human immunodeficiency virus infection at which to initiate highly active antiretroviral therapy (HAART) among asymptomatic persons is a core question. A cohort approach using longitudinal data from the US Multicenter AIDS Cohort Study was used to mimic a clinical trial to assess the risk of acquired immunodeficiency syndrome (AIDS) by timing of therapy. Three treatment groups were defined according to CD4(+) count (cells/microl) at HAART initiation between July 1995 and January 2000: <200 (deferral to <200, n = 127), 200-349 (deferral to 200-349, n = 130), and 350-499 (immediate treatment, n = 92). Survival analysis was used to compare time to AIDS between groups from the index visit until July 2000. The index visit for the immediate group was the one prior to HAART initiation. For the deferral groups, the index visit was a randomly selected, pre-HAART, AIDS-free visit after July 1990 at which CD4(+) counts were 350-499 cells/microl. This strategy accounted for lead time bias. Compared with immediate treatment, the relative hazards of AIDS were 2.68 (p = 0.003) and 1.05 (p = 0.897) for deferral to <200 cells/microl and 200-349 cells/ micro l, respectively. These results support recent US public health guidelines for deferring HAART initiation until a count of <350 cells/microl. Furthermore, results suggest a potential threshold for HAART initiation in the neighborhood of 275 cells/microl.     

Access to antiretroviral treatment among French HIV infected injection drug users: the influence of continued drug use. MANIF 2000 Study Group

STUDY OBJECTIVE: To determine the influence of continued drug use and its perception by prescribing physicians on access to antiretroviral treatment among French HIV infected injection drug users (IDUs). DESIGN: Cross sectional including enrollment data (October 1995-1996) of the cohort study MANIF 2000. Access to treatment is compared in three groups: former IDUs (n = 68) and active IDUs whether or not this behaviour remains undetected (n = 38) or detected (n = 17) by physicians. SETTING: Hospital departments for specialist AIDS care in south eastern France and inner suburbs of Paris. PATIENTS: All enrolled patients with CD4+ cell counts < 400 with detailed clinical history, access to treatment, risk behaviours, and past drug use as reported by both physicians and patients (n = 123). MAIN RESULTS: A minority (43.9%) already received an antiretroviral treatment. Active IDUs had worst socioeconomic and psychological conditions but only those detected by physicians were considered as poorly compliant. Logistic regression showed that, with respect to ex-IDUs and independently of clinical stage, active IDUs, whether or not they were perceived as such by physicians, were threefold more likely not to receive antiretroviral treatment. CONCLUSIONS: Even among French HIV infected IDUs who have regular access to AIDS specialised hospital care, continued drug use reduced the likelihood of being prescribed antiretroviral treatment. To reduce delays in access to new treatments, specific efforts must be devoted towards both AIDS specialists and IDU patients to overcome current stereotypes of non-compliance associated with continued injection.     

Rates of inappropriate antiretroviral prescription among injection drug users

Background  

Although the survival benefits of antiretroviral therapy (ART) for the treatment of HIV infection are well established, the clinical management of HIV disease continues to present major challenges. There are particular concerns regarding access to appropriate HIV treatment among HIV-infected injection drug users (IDU).     

高效抗逆转录病毒治疗的不良反应

高效抗逆转录病毒治疗(HAART)的应用大大降低了艾滋病相关的发病率和死亡率。但是,所有的抗逆转录病毒药物都有短期的或者是长期的不良反应,例如高乳酸血症、乳酸酸中毒、肝脏毒性、高血糖、脂肪代谢异常、增加血友病患者出血的危险、骨质疏松以及皮疹等等,不良反应严重影响了HAART的临床应用。本文就以上问题进行了综述。     

Access to highly active antiretroviral therapy (HAART) in the WHO European Region 2003-2005

AIMS: To assess changes in access to highly active antiretroviral therapy (HAART) between the end of 2002 and the end of 2005, and to review the capacity for further HAART scale-up in the then 52 Member States of the WHO European Region. METHODS: Analysis of data from four surveys evaluating access to HAART, supplemented by regional estimates of the number of people receiving HAART. Changes in access to HAART are evaluated in terms of changes in the number of people receiving HAART over time and changes in country-level HAART coverage. RESULTS: During 2003-2005, the total number of individuals receiving HAART increased by an estimated 101,000, from 242,000 to 343,000 (a 42% increase); 85,000 were in the west region (a 36% increase) and 16,000 in the centre and east regions (a 229% increase). The number of countries providing "high' coverage with HAART (>75% of those in need receiving it) increased from 29 to 38, and the number of countries providing no HAART declined from eight to four. CONCLUSIONS: Despite high and increasing coverage in many European countries, access to HAART remained inequitable in terms of geographical location. By the end of 2005, all countries in the west provided "high' HAART coverage as compared with half of countries in the centre and east. Six east countries still provided poor or no HAART coverage. Countries must address how to further equitably increase the number of people receiving HAART.     

The parametric g-formula to estimate the effect of highly active antiretroviral therapy on incident AIDS or death

The parametric g‐formula can be used to contrast the distribution of potential outcomes under arbitrary treatment regimes. Like g‐estimation of structural nested models and inverse probability weighting of marginal structural models, the parametric g‐formula can appropriately adjust for measured time‐varying confounders that are affected by prior treatment. However, there have been few implementations of the parametric g‐formula to date. Here, we apply the parametric g‐formula to assess the impact of highly active antiretroviral therapy on time to acquired immune deficiency syndrome (AIDS) or death in two US‐based human immunodeficiency virus cohorts including 1498 participants. These participants contributed approximately 7300 person‐years of follow‐up (49% exposed to highly active antiretroviral therapy) during which 382 events occurred and 259 participants were censored because of dropout. Using the parametric g‐formula, we estimated that antiretroviral therapy substantially reduces the hazard of AIDS or death (hazard ratio = 0.55; 95% confidence limits [CL]: 0.42, 0.71). This estimate was similar to one previously reported using a marginal structural model, 0.54 (95% CL: 0.38, 0.78). The 6.5‐year difference in risk of AIDS or death was 13% (95% CL: 8%, 18%). Results were robust to assumptions about temporal ordering, and extent of history modeled, for time‐varying covariates. The parametric g‐formula is a viable alternative to inverse probability weighting of marginal structural models and g‐estimation of structural nested models for the analysis of complex longitudinal data. Copyright © 2012 John Wiley & Sons, Ltd.     

长期高效抗逆转录病毒治疗后的代谢异常改变

HAART的应用大大降低了艾滋病患者的死亡率,但同时也增加了各种不良反应,其中远期不良反应主要与代谢异常改变有关,如脂肪重新分布、胰岛素抵抗、血脂异常、骨质疏松等,不仅大大增加了患者发生心血管疾病的风险,对肝肾功能也有不同程度的影响.HAART因耗时长、进展慢等导致其原因所引起的不良反应不易被察觉,也未得到足够的重视.本文对长期HAART后出现的代谢改变及其机制作一综述.     

Adherence to highly active antiretroviral therapy in Spain. A meta-analysis

Objectives

To estimate the percentage of adherence to highly-active antiretroviral therapy (HAART) in Spanish observational studies and to identify the variables associated with adherence.

Methods

Seven electronic databases were used to locate the studies. Six inclusion criteria were established. Two coders codified the variables independently. Intercoder reliability was calculated. Publication bias was analyzed through the Begg, Egger and Trim and Fill tests. Homogeneity was evaluated using the Q test and the l² index. A random effects model was assumed to estimate both the overall percentage of adherence and to explain heterogeneity.

Results

This meta-analysis included 23 observational studies, yielding a total of 34 adherence estimates. The sample was composed of 9,931 HIV-positive individuals (72% men) older than 18 years under treatment with HAART. The percentage of patients adhering to an intake of >90% of the prescribed antiretroviral drugs was 55%. Wide heterogeneity was detected (I² = 91.20; 95%CI: 88.75-93.13). Adherence was mainly measured using a single strategy (47.8%), the most widely used being self-report (48.7%). In the univariate analysis, the following factors were significant: infection stages A (β = 0.68, p <0.001) and B (β = -0.56, p <0.01), viral loads >200 copies/ml (β = -0.41, p <0.05) and <200 (β = 0.39, p <0.05), and university education (β = -0.66, p<0.05).

Conclusions

The overall percentage of adherence was 55%, although this value may be an overestimate. Adherence was associated with infection stage A and with a viral load of <200 copies/ml.     

抗HIV治疗失败后HIV 1耐药基因的变异

目的研究抗人免疫缺陷病毒（HIV)治疗失败后,HIV 1遗传基因变异情况,并分析其耐药性。方法选取抗HIV治疗失败的57例患者(其中采用D4T/3TC/NVP治疗方案者45例,3TC/AZT/NVP方案者7例,3TC/TDF/克立芝方案者5例）,从其血浆中提取病毒RNA,运用逆转录-聚合酶链反应（RT PCR）和套式PCR扩增HIV 1 pol区基因片段,并对扩增的目的片段进行测序,将测序结果提交Web站点（http://HIVdb.stanford.edu）,分析耐药变异情况。结果3种治疗方案治疗失败者均出现耐药。57例患者,7例发生针对蛋白酶抑制剂的位点变异,其中1例（1.75%）M46IM蛋白酶抑制剂的位点变异,导致了抗ATV/r、FPV/r、IDV/r、LPV/r的潜在低度耐药和抗NFV的高度耐药;32例（56.14%）患者体内HIV 1发生了逆转录酶基因变异,且均对不同逆转录酶抑制剂产生了耐受性,其中14例（43.75%,14/32）患者对斯坦福数据库中的11种药物全都耐药,且11例（78.57%）治疗方案为D4T/3TC/NVP。TDF、克立芝等二线药物的治疗方案突变位点少于一线药物D4T、3TC、NVP、AZT。结论耐药变异是导致抗HIV治疗失败的主要原因。在开展抗病毒治疗过程中,应适时进行耐药性检测,以获得较好疗效。     

湖南省艾滋病患者抗病毒治疗后耐药性分析

目的了解湖南省艾滋病患者接受免费抗病毒治疗的效果以及人免疫缺陷病毒(HIV)的耐药情况,为改善该省的高效抗逆转录病毒治疗效果,指导临床医生用药提供科学的依据。方法收集湖南省衡阳市抗病毒治疗6个月以上的252例HIV感染者的血标本,进行病毒载量检测,其中32例病毒载量10~3拷贝/mL,对此32份样本进行进一步的HIV基因型耐药检测。结果测得的31个序列中,发生突变的样本18份,其中13份(5.16%,13/252)对蛋白酶抑制剂(PIs)、核苷类逆转录酶抑制剂(NRTIs)以及非核苷类逆转录酶抑制剂(NNRTIs)这3类抗逆转录病毒药物有耐药突变;对PIs、NRTIs和NNRTIs均耐药者1例(0.40%),对NRTIs和NNRTIs均耐药者9例(3.57%),对NNRTIs耐药者3例(1.19%)。同时发现M184V、K103N、Y181CG、G190A引起NRTIs和NNRTIs高水平耐药的重要突变位点。结论湖南省艾滋病治疗者中,PIs耐药发生率极低,NRTIs和NNRTIs的耐药发生率相对较高;已出现NNRTIs高水平的多药耐药。但总体耐药的发生仍处于较低水平。     

艾滋病高效抗逆转录治疗的耐药发生与控制研究进展

随着高效抗逆转录疗法的运用与推广,HIV感染者的寿命得到延长。HIV是反转录病毒,其反转录酶在HIV复制时可进行DNA复制但无校正能力,导致出错率高,加之药物选择压力等因素,其耐药问题成为治疗失败的主要原因。阐明抗逆转录治疗耐药发生发展过程,对艾滋病控制与治疗具有重要意义,本文就HIV耐药产生途径与趋势、耐药相关影响因素以及降低耐药率策略进行综述。     

Alcohol use and incarceration adversely affect HIV-1 RNA suppression among injection drug users starting antiretroviral therapy

We conducted this study among HIV-infected injection drug users to determine the effect of self-reported alcohol use and prior incarceration at the time of initiating antiretroviral therapy on subsequent HIV-1 RNA suppression. We examined the demographics, recent incarceration history, and drug and alcohol use history from the Vancouver Injection Drug User Study (VIDUS) questionnaire closest to the date of initiating antiretroviral therapy. We linked these data to the HIV/AIDS Drug Treatment Program. There were 234 VIDUS participants who accessed antiretroviral therapy through the Drug Treatment Program from August 1, 1996, to July 31, 2001. In terms of illicit drug use, 196 (84%) reported injecting heroin and cocaine at the time of initiating antiretroviral therapy. Multiple logistic regression revealed that in the 6 months prior to initiating antiretroviral therapy, alcohol use (adjusted odds ratio [AOR] 0.32; 95% CI 0.13–0.81) and incarceration (AOR 0.22; 95% CI 0.09–0.58) were independently associated with lower odds of HIV-1 RNA suppression. Factors positively associated with HIV-1 RNA suppression included: adherence (AOR 1.27; 95% CI 1.06–1.51); lower baseline HIV-1 RNA (AOR 1.30: 95% CI 1.01–1.66); highly active antiretroviral therapy (AOR 4.10; 95% CI 1.56–10.6); months on therapy (AOR 1.1; 95% CI 1.06–1.14). Among HIV-infected injection drug users who were on antiretroviral therapy, any alcohol use and incarceration in the 6 months prior to initiating antiretroviral therapy were negatively associated with achieving HIV-1 RNA suppression. In addition to addition treatment for active heroin and cocaine use, the identification and treatment of alcohol problems should be supported in this setting. As well, increased outreach to HIV-infected drug users recently released from prison to ensure continuity of care needs to be further developed.