HIV/HCV共感染者抗逆转录病毒治疗后免疫恢复情况

由于具有相同的传播途径,人类免疫缺陷病毒(Human immunodeficiency virus,HIV)和丙型肝炎病毒(Hepatitis C virus,HCV)共感染非常普遍,但是关于合并感染的程度,两种病毒之间的相互关系,在艾滋病抗逆转录病毒治疗(Antiretroviral therapy,ART)前后,HCV合并感染对HIV患者免疫细胞恢复的影响仍不明确。为了通过分析CD4⁺和CD8⁺T淋巴细胞数的变化,以了解辽宁省HIV/HCV共感染者ART后免疫恢复的情况,本研究从辽宁省艾滋病抗病毒治疗数据库中筛选符合要求的HIV感染者和HIV/HCV共感染者,收集感染者基本人口学资料及HCV抗体检测结果、HIV/HCV共感染途径等资料。采用t检验或卡方检验进行组间比较,采用Kaplan-Meier乘积极限法绘制生存分析函数图。结果显示,本研究共纳入HIV感染者12742人,HIV/HCV共感染者340人。HIV感染者和HIV/HCV共感染者的不同人口学特征均差异显著(P<0.001)。HIV感染和HIV/HCV共感染者ART治疗后CD4⁺细胞数和CD4⁺/CD8⁺比值显著升高(P<0.05),CD8⁺细胞数比ART前显著下降(P<0.05)。HIV/HCV共感染者随着ART时长,CD4⁺T淋巴细胞数恢复情况始终显著低于HIV感染者(P<0.05)。生存分析曲线表明,HCV/HIV共感染者从艾滋病诊断开始随着ART的治疗CD4⁺细胞恢复情况显著低于HIV感染者,Log-Rank检验统计量为4.483(P=0.034)。本研究揭示,HCV感染对ART患者CD4⁺和CD8⁺T淋巴细胞的恢复有影响。ART后HIV/HCV共感染者中CD4⁺T淋巴细胞计数的改善低于HIV单一感染者,并且单一感染患者对ART的反应比合并感染患者更好。因此,建议在启动ART之前,对每个感染HIV的患者进行HCV抗体筛查。     

A Randomized Trial of Time-Limited Antiretroviral Therapy in Acute/Early HIV Infection

Background

It has been proposed that initiation of antiretroviral treatment (ART) very soon after establishment of HIV infection may be beneficial by improving host control of HIV replication and delaying disease progression.

Methods

People with documented HIV infection of less than 12 months’ duration in Baltimore MD and seven Canadian sites were randomized to either a) observation and deferred ART, or b) immediate treatment with ART for 12 months. All subjects not receiving ART were followed quarterly and permanent ART was initiated according to contemporaneous treatment guidelines. The endpoint of the trial was total ART-free time from study entry until initiation of permanent ART.

Results

One hundred thirteen people were randomized, 56 to the observation arm and 57 to the immediate treatment arm. Twenty-three had acute (<2 months) infection and 90 early (2–12 months) infection. Of those randomized to the immediate treatment arm, 37 completed 12 months of ART according to protocol, 9 declined to stop ART after 12 months, and 11 were nonadherent to the protocol or lost to follow-up. Comparing those in the observation arm to either those who completed 12 months of ART or all 56 who were randomized to immediate ART, there was no significant difference between the arms in treatment-free interval after study entry, which was about 18 months in both arms.

Conclusions

This study did not find a benefit from administration of a brief, time-limited (12-month) course of ART in acute or early HIV infection.

Trial Registration

ClinicalTrials.gov NCT00106171     

The Cameroon Mobile Phone SMS (CAMPS) Trial: A Randomized Trial of Text Messaging versus Usual Care for Adherence to Antiretroviral Therapy

Background

Mobile phone technology is a novel way of delivering health care and improving health outcomes. This trial investigates the use of motivational mobile phone text messages (SMS) to improve adherence to antiretroviral therapy (ART) over six months.

Methodology/Principal Findings

CAMPS was a single-site randomized two-arm parallel design trial in Yaoundé, Cameroon. We enrolled and randomized HIV-positive adults on ART, aged 21 years and above to receive a weekly standardized motivational text message versus usual care alone. The primary outcome was adherence measured using a visual analogue scale (VAS), number of doses missed (in the week preceding the interview) and pharmacy refill data. Outcomes were measured at 3 and 6 months. Service providers and outcome assessors were blinded to allocation. Analysis was by intention-to-treat. Between November and December 2010, 200 participants were randomized, with 101 in the intervention group and 99 in the control group. At 6 months, overall retention was 81.5%. We found no significant effect on adherence by VAS>95% (risk ratio [RR] 1.06, 95% confidence interval [CI] 0.89, 1.29; p = 0.542; reported missed doses (RR 1.01, 95% CI 0.87, 1.16; p>0.999) or number of pharmacy refills (mean difference [MD] 0.1, 95% CI: 0.23, 0.43; p = 0.617. One participant in the intervention arm reported a possible disclosure of status.

Conclusions/Significance

Standardized motivational mobile phone text messages did not significantly improve adherence to ART in this study. Other types of messaging or longer term studies are recommended.

Registration

1. Pan-African Clinical Trials Registry; PACTR201011000261458 2. Clinicaltrials.gov; {"type":"clinical-trial","attrs":{"text":"NCT01247181","term_id":"NCT01247181"}}NCT01247181     

Retention in Care of Adult HIV Patients Initiating Antiretroviral Therapy in Tigray,Ethiopia: A Prospective Observational Cohort Study

Introduction

Although Ethiopia has been scaling up the antiretroviral therapy (ART) services, low retention in care of patients remains one of the main obstacles to treatment success. We report data on retention in care and its associated determinants in Tigray, Ethiopia.

Methods

We used data from the CASA project, a prospective observational and multi-site study of a cohort of HIV-infected patients who initiated ART for the first time in Tigray. Four participating health facilities (HFs) located in the South of Tigray were considered for this study. Patients were followed for one year after ART initiation. The main outcome measure was represented by the current retention in care, defined as the proportion of patients who were alive and receiving ART at the same HF one year after ART initiation. Patients who started ART between January 1, 2013 and December 31, 2013 were included in this analysis. Patients were followed for one year after ART initiation. The determinants of retention were analysed using univariate and multivariate Cox Proportional Hazards model with robust sandwich estimates to account for within HF correlation.

Results

The four participating HFs in Tigray were able to retain overall 85.1% of their patients after one year from starting ART. Loss to follow-up (5.5%) and transfers to other HF (6.6) were the main determinant of attrition. A multivariate analysis shows that the factors significantly associated with retention were the type of HF, gender and active TB. Alamata health center was the HF with the highest attrition rate (HR 2.99, 95% CI: 2.77–3.23). Active TB (HR 1.72, 95% CI: 1.23–2.41) and gender (HR 1.64, 95% CI: 1.10–2.56) were also significantly associated with attrition.

Conclusions

Although Ethiopia has significantly improved access to the ART program, achieving and maintaining a satisfactory long-term retention rate is a future goal. This is difficult because of different retention rates among HFs. Moreover specific interventions should be directed to people of different sex to improve retention in care in male population.     

Survival and HLA-B*57 in HIV/HCV Co-Infected Patients on Highly Active Antiretroviral Therapy (HAART)

Background and aims

HLA class I alleles, in particular HLA-B*57, constitute the most consistent host factor determining outcomes in untreated HCV- and HIV-infection. In this prospective cohort study, we analysed the impact of HLA class I alleles on all-cause mortality in patients with HIV-, HCV- and HIV/HCV- co-infection receiving HAART.

Methods

In 2003 HLA-A and B alleles were determined and patients were prospectively followed in 3-month intervals until 2013 or death. HLA-A and B alleles were determined by strand-specific oligonucleotide hybridisation and PCR in 468 Caucasian patients with HCV- (n=120), HIV- (n=186) and HIV/HCV-infection (n=162). All patients with HIV-infection were on HAART. In each patient group, HLA class I-associated survival was analysed by Kaplan-Meier method and Cox regression analysis.

Results

At recruitment the proportion of patients carrying a HLA-B*57 allele differed between HIV- (12.9%) and HCV-infection (4.2%). Kaplan Meier analysis revealed significantly increased mortality in HLA-B*57-positive patients with HIV-infection (p=0.032) and HIV/HCV-co-infection (p=0.004), which was apparently linked to non-viral infections. Cox logistic regression analysis confirmed HLA-B*57 (p=0.001), serum gamma-glutamyltranspeptidase (p=0.003), serum bilirubin (p=0.022) and CD4 counts (p=0.041) as independent predictors of death in HIV-infected patients.

Conclusion

Differences in the prevalence of HLA-B*57 at study entry between HIV- and HCV- infected patients may reflect immune selection in the absence of antiviral therapy. When patients were treated with HAART, however, HLA-B*57 was associated with increased mortality and risk to die from bacterial infections and sepsis, suggesting an ambiguous role of HLA-B*57 for survival in HIV/HCV infection depending on the circumstances.     

Long-Term Survival in HIV Positive Patients with up to 15 Years of Antiretroviral Therapy

Background

Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models.

Methods

Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models.

Results

The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2–10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5–2.9) for CD4 = 350–499 cells/µl; and 1.5 (95% CI: 1.1–2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment.

Conclusion

Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.     

Antiretroviral Therapy Reduces HIV Transmission in Discordant Couples in Rural Yunnan,China

Background

Although HIV treatment as prevention (TasP) via early antiretroviral therapy (ART) has proven to reduce transmissions among HIV-serodiscordant couples, its full implementation in developing countries remains a challenge. In this study, we determine whether China''s current HIV treatment program prevents new HIV infections among discordant couples in rural China.

Methods

A prospective, longitudinal cohort study was conducted from June 2009 to March 2011, in rural Yunnan. A total of 1,618 HIV-discordant couples were eligible, 1,101 were enrolled, and 813 were followed for an average of 1.4 person-years (PY). Routine ART was prescribed to HIV-positive spouses according to eligibility (CD4<350 cells/µl). Seroconversion was used to determine HIV incidence.

Results

A total of 17 seroconversions were documented within 1,127 PY of follow-up, for an overall incidence of 1.5 per 100 PY. Epidemiological and genetic evidence confirmed that all 17 seroconverters were infected via marital secondary sexual transmission. Having an ART-experienced HIV-positive partner was associated with a lower rate of seroconvertion compared with having an ART-naïve HIV-positive partner (0.8 per 100 PY vs. 2.4 per 100 PY, HR = 0.34, 95%CI = 0.12–0.97, p = 0.0436). While we found that ART successfully suppressed plasma viral load to <400 copies/ml in the majority of cases (85.0% vs. 19.5%, p<0.0001 at baseline), we did document five seroconversions among ART-experienced subgroup.

Conclusions

ART is associated with a 66% reduction in HIV incidence among discordant couples in our sample, demonstrating the effectiveness of China''s HIV treatment program at preventing new infections, and providing support for earlier ART initiation and TasP implementation in this region.     

Impact of HIV Comprehensive Care and Treatment on Serostatus Disclosure among Cameroonian Patients in Rural District Hospitals

This work aimed to analyze the rate of disclosure to relatives and friends over time and to identify factors affecting disclosure among seropositive adults initiating antiretroviral therapy (ART) in rural district hospitals in the context of decentralized, integrated HIV care and task-shifting to nurses in Cameroon. Stratall was a 24-month, randomized, open-label trial comparing the effectiveness of clinical monitoring alone with laboratory plus clinical monitoring on treatment outcomes. It enrolled 459 HIV-infected ART-naive adults in 9 rural district hospitals in Cameroon. Participants in both groups were sometimes visited by nurses instead of physicians. Patients with complete data both at enrolment (M0) and at least at one follow-up visit were included in the present analysis. A mixed Poisson regression was used to estimate predictors of the evolution of disclosure index over 24 months (M24).The study population included 385 patients, accounting for 1733 face-to-face interviews at follow-up visits from M0 to M24. The median [IQR] number of categories of relatives and friends to whom patients had disclosed was 2 [1]–[3] and 3 [2]–[5] at M0 and M24 (p-trend<0.001), respectively. After multiple adjustments, factors associated with disclosure to a higher number of categories of relatives and friends were as follows: having revealed one’s status to one’s main partner, time on ART, HIV diagnosis during hospitalization, knowledge on ART and positive ratio of follow-up nurse-led to physician-led visits measuring task-shifting. ART delivered in the context of decentralized, integrated HIV care including task-shifting was associated with increased HIV serological status disclosure.     

Week 120 Efficacy of Tenofovir,Lamivudine and Lopinavir/r-Based Second-Line Antiretroviral Therapy in Treatment-Experienced HIV Patients

Background

Tenofovir (TDF) and ritonavir-boosted lopinavir (LPV/r) were not introduced to China as second-line medications until 2009. The efficacy and safety of TDF/3TC/LPV/r based second-line regimen have not been evaluated in Chinese HIV patients who failed first-line regimens.

Methods

This was a multicenter cohort study recruiting patients from Beijing, Shanghai, Guangdong, and Henan provinces between November 2008 and January 2010. Eighty HIV infected patients failing first-line regimens with serum creatinine lower than 1.5 times the upper limit of normal received TDF+ lamivudine (3TC)+ LPV/r were followed up for 120 weeks. CD4 cell count, viral load, and estimated glomerular filtration rate (eGFR) were monitored at each visit.

Results

At baseline, 31.2% and 48.8% of patients had moderate/high-level resistance to TDF and 3TC, respectively; while 2.5% of patients had only low-level resistance to LPV/r. During 120 weeks of follow-up, virological suppression rate reached over 70% (<40 copies/ml) and 90% (<400 copies/ml), and median CD4 cell count increased from 157 cells/μL at baseline to 307 cells/μL at week 120. Baseline drug-resistance mutations had no impact on the efficacy of second-line antiretroviral therapy. Median eGFR dropped from 104.7 ml/min/1.73m² at baseline to 95.6 ml/min/1.73m² at week 24 and then recovered after week 96.

Conclusion

This study for the first time demonstrated that TDF+ 3TC+ LPV/r was efficacious as second-line regimen with acceptable nephrotoxicity profiles in patients who failed zidovudine or stavudine based first-line regimens in China.

Trial Registration

ClinicalTrials.gov NCT00872417     

Environmental Factors Related to Pulmonary Tuberculosis in HIV-Infected Patients in the Combined Antiretroviral Therapy (cART) Era

The aim of our study was to evaluate the seasonal variations and whether short-term exposure to environmental risk factors, such as climate and air pollution, is associated with PTB-related hospital admissions in human immunodeficiency virus (HIV)-infected patients in Spain during the era of combined antiretroviral therapy (cART). A retrospective study was carried out using data from the Minimum Basic Data Set (MBDS) and the State Meteorological Agency (AEMET) of Spain. The primary outcome variable was hospital admissions with PTB diagnosis. The environmental risk factors evaluated were season, temperature, humidity, NO₂, SO₂, O₃, PM₁₀, and CO. Overall, HIV-infected patients had a lower frequency of PTB-related hospital admissions in summer (22.8%) and autumn (22.4%), but higher values in winter (26.6%) and spring (28.2%). Using a Bayesian temporal model, PTB-related hospital admissions were less frequent in summer-autumn and more abundant in winter-spring during the first years of follow-up. During the later years of follow-up, the seasonal trends continued resulting in the lowest values in autumn and the highest in spring. When considering short-term exposure to environmental risk factors, lower temperatures at 1 week (odds ratio (OR) = 1.03; p = 0.008), 1.5 weeks (OR = 1.03; p<0.001), 2 weeks (OR = 1.04; p<0.001), and 3 weeks (OR = 1.03; p<0.001) prior to PTB admission. In addition, higher concentration of NO₂ at the time of admission were significantly associated with higher likelihoods of PTB-related hospital admission in HIV-infected patients when 1.5 weeks (OR = 1.1; p = 0.044) and 2 weeks (OR = 1.21; p<0.001) were used as controls. Finally, higher concentration of SO₂ at 1.5 weeks prior to PTB admission was significantly associated with a higher likelihood of PTB-related hospital admissions (OR = 0.92; p = 0.029). In conclusion, our data suggest an apparent seasonal variation in hospital admissions of HIV-infected patients with a PTB diagnosis (summer/autumn vs. winter/spring), as well as a link to short-term exposure to environmental risk factors, such as temperature and ambient NO₂ and SO₂.     

Prevalence and Predictors of Major Depression in HIV-Infected Patients on Antiretroviral Therapy in Bamenda, a Semi-Urban Center in Cameroon

Recent blue-ribbon panel reports have concluded that HIV treatment programs in less wealthy countries must integrate mental health identification and treatment into normal HIV clinical care and that research on mental health and HIV in these settings should be a high priority. We assessed the epidemiology of depression in HIV patients on antiretroviral therapy in a small urban setting in Cameroon by administering a structured interview for depression to 400 patients consecutively attending the Bamenda Regional Hospital AIDS Treatment Center. One in five participants met lifetime criteria for MDD, and 7% had MDD within the prior year. Only 33% had ever spoken with a health professional about depression, and 12% reported ever having received depression treatment that was helpful or effective. Over 2/3 with past-year MDD had severe or very severe episodes. The number of prior depressive episodes and the number of HIV symptoms were the strongest predictors of past-year MDD. The prevalence of MDD in Cameroon is as high as that of other HIV-associated conditions, such as tuberculosis and Hepatitis B virus, whose care is incorporated into World Health Organization guidelines. The management of depression needs to be incorporated in HIV-care guidelines in Cameroon and other similar settings.     

Estimated Costs for Delivery of HIV Antiretroviral Therapy to Individuals with CD4+ T-Cell Counts >350 cells/uL in Rural Uganda

Background

Evidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up.

Methods

Within a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: {"type":"clinical-trial","attrs":{"text":"NCT01479634","term_id":"NCT01479634"}}NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing.

Findings

Among 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451–716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of $529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by $100–200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel, $106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals.

Conclusions

In a Ugandan HIV clinic, ART delivery costs—including VL testing—for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions.