Estimating the effect of antiretroviral treatment during HIV seroconversion: impact of confounding in observational data

Objective

To assess whether treatment with antiretroviral drugs within the first 3 months of infection with HIV affects medium‐term health outcomes.

Design and methods

Data from 20 cohorts in Europe and Australia were used Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE). Analysis was restricted to persons seroconverting in 1988–1998 who started antiretroviral treatment in the first 3 months or 1–2 years from seroconversion. The relationship between times to low CD4 count, AIDS and death and time of initiation of treatment was estimated using proportional hazards models.

Results

Seroconversion illness was more common in those who began antiretroviral treatment in the first 3 months (73%) than in those who started treatment within 1–2 years post‐seroconversion (33%). Subjects receiving early antiretroviral treatment had times to AIDS and to CD4 counts <200 cells/μL that were intermediate between those of subjects starting treatment within 1–2 years and those of the subset of these subjects starting treatment within 1–2 years who also had a prior CD4 count of >350 cells/μL and no prior AIDS diagnosis.

Conclusions

On the basis of these analyses, the effect of antiretroviral treatment initiation during HIV seroconversion is uncertain. It may result in lower rates of progression compared with starting antiretroviral treatment at 1–2 years, but the early antiretroviral treatment group had a similar or even higher incidence of low CD4 counts and AIDS events than the group who started antiretroviral treatment within 1–2 years with CD4 counts over 350 cells/μL and no prior AIDS diagnosis. Estimates of the effect of early treatment are probably confounded with a number of factors, including, in particular, reasons for treatment initiation.

     

Successful optimization of antiretroviral regimens in treatment‐experienced people living with HIV undergoing liver transplantation

Modern antiretroviral therapy (ART) extends life expectancy for people living with HIV (PLWH). However, most older PLWH (≥50 years) “aged” with HIV and were exposed to historical HIV care practices and older, more toxic ART. In PLWH with exposure to older and multiple ART regimens, the drug interactions between ART frequently used in treatment‐experienced persons and commonly used immunosuppressants remain a significant challenge. However, the advent of newer ART classes (eg, integrase non‐strand transfer inhibitors) and more advanced HIV genetic resistance testing may allow optimization of ART regimens with minimal drug interactions. Here, we present a case series of three PLWH whose complicated ART interacted (or was at risk for interacting) with their post–liver transplant immunosuppression. After a review of their proviral DNA resistance testing, they successfully transitioned onto safer integrase non‐strand transfer inhibitor‐containing ART regimens without viral blips or evidence of organ rejection.     

HIV耐药评估和预防策略

HIV耐药会影响抗病毒治疗的长期疗效,使得艾滋病流行结束于2030年的目标难以实现。不同国家采用不同策略来预防和评估HIV耐药的产生和传播。目前,高收入国家对HIV感染者进行个体耐药检测。多数中低收入国家采用WHO提出的群体监测策略,监测耐药早期预警指标,评估治疗人群获得性耐药,监测治疗前耐药、传播性耐药及18月龄以下儿童耐药等措施。我国采用HIV耐药个体检测和群体监测相结合的防控策略。     

Extended antiretroviral treatment interruption in HIV-infected patients with long-term suppression of plasma HIV RNA

OBJECTIVES: Evaluation of extended treatment interruption (TI) in chronic HIV infection among patients successfully treated with antiretroviral therapy. METHODS: An observational analysis of 25 patients in a prospectively followed cohort with chronic HIV infection, viral loads <500 HIV-1 RNA copies/mL for at least 6 months, and an interruption in therapy of >/=28 days duration was carried out. Follow up was divided into 3-month time periods for analysis. The effects of time period, stratification group and stratification group by time period interactions on CD4 counts were tested using a mixed model. Univariate comparisons among patient characteristics and responses were performed using Fisher's exact test or the Wilcoxon rank sum test. RESULTS: At initiation of TI, the median CD4 count was 799 cells/microL. TI duration was a median of 7.1 months. HIV RNA rebounded to a median maximum level of 75 000 copies/mL. Maximum viral rebound was significantly greater in patients who were male, had lipodystrophy and had zenith HIV RNA prior to TI of >/=50 000 copies/mL. Lower CD4 cell counts were observed during TI in patients with lipodystrophy, zenith HIV RNA >/=50 000 copies/mL, history of AIDS, HIV infection >/=5 years and presuppression CD4 count 相似文献   

HIV in the UK 1980-2006: reconstruction using a model of HIV infection and the effect of antiretroviral therapy

BACKGROUND: Given the extent of data on the natural history of HIV infection and the effect of antiretroviral therapy (ART), it should be possible to develop a model that encapsulates and can simulate these processes, providing a means of exploring various clinical and epidemiological questions. We aimed to develop such a model and use it to reconstruct the HIV-infected population in the UK to 2006. METHODS: A stochastic computer simulation model was developed that incorporates much of our understanding of the underlying processes of HIV disease progression and the effect of ART. RESULTS: The model generally fitted well to a range of data in treated and untreated infection. UK reconstructions suggest that, of around 68 500 people alive with HIV infection at the end of 2006, around 34,000 (49%) were on ART, with an increasing proportion of these on first-line regimens (75% in 2006). The number of patients who have failed virologically on the original three main drug classes (estimated at around 4300 in 2006) is increasing only gradually, and an increasing proportion of these patients have suppressed viral load. CONCLUSIONS: The beneficial effects of ART at a population level look set to continue as the number of patients exhausting the three original drug classes remains small.     

Prediction of response to antiretroviral therapy by human experts and by the EuResist data‐driven expert system (the EVE study)

Objectives

The EuResist expert system is a novel data‐driven online system for computing the probability of 8‐week success for any given pair of HIV‐1 genotype and combination antiretroviral therapy regimen plus optional patient information. The objective of this study was to compare the EuResist system vs. human experts (EVE) for the ability to predict response to treatment.

Methods

The EuResist system was compared with 10 HIV‐1 drug resistance experts for the ability to predict 8‐week response to 25 treatment cases derived from the EuResist database validation data set. All current and past patient data were made available to simulate clinical practice. The experts were asked to provide a qualitative and quantitative estimate of the probability of treatment success.

Results

There were 15 treatment successes and 10 treatment failures. In the classification task, the number of mislabelled cases was six for EuResist and 6–13 for the human experts [mean±standard deviation (SD) 9.1±1.9]. The accuracy of EuResist was higher than the average for the experts (0.76 vs. 0.64, respectively). The quantitative estimates computed by EuResist were significantly correlated (Pearson r=0.695, P<0.0001) with the mean quantitative estimates provided by the experts. However, the agreement among experts was only moderate (for the classification task, inter‐rater κ=0.355; for the quantitative estimation, mean±SD coefficient of variation=55.9±22.4%).

Conclusions

With this limited data set, the EuResist engine performed comparably to or better than human experts. The system warrants further investigation as a treatment‐decision support tool in clinical practice.     

An audit of antiretroviral treatment use in HIV-infected patients in a London clinic: the limitations of observational databases when auditing antiretroviral treatment use

Objective

To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines.

Methods

All patients under follow‐up between 1st January 2000 and 1st January 2001 were included. The most recent CD4 count and HIV RNA level prior to 1st January 2001, and the nadir CD4 count and peak HIV RNA level over follow‐up, were used to identify which patients should be receiving HAART according to the guidelines.

Results

One thousand two hundred and sixty‐four patients were included in the analysis (63.8% homosexual, 29.0% heterosexual risk; 72.9% white; 79.2% male). Almost half of patients had ever had a CD4 count below 200 cells/µL and over 80% had previously had a viral load above 4 log₁₀ HIV‐1 RNA copies/mL. Under 2000 BHIVA guidelines, treatment would be recommended in 77.4% patients. Overall, 819 patients were receiving ARV therapy. Two hundred and eighty‐five patients were not receiving treatment when guidelines suggest they should (including 33 patients who were receiving regimens not recommended in the guidelines). These patients were younger, less likely to be homosexual and had higher CD4 nadirs than those who were receiving ARV treatment. Almost half of these patients had previously received ARV therapy but were not currently receiving it.

Conclusion

Only a small proportion of patients at our centre were not receiving ARV treatment in line with national guidelines. While genuine reasons may exist for these departures from optimal care, this may simply reflect the limitations of using observational databases when auditing treatment use in a clinic setting.

     

Association of social stress,illicit drug use,and health beliefs with nonadherence to antiretroviral therapy

OBJECTIVE: To assess the roles of socioeconomic status, social stability, social stress, health beliefs, and illicit drug use with nonadherence to antiretroviral therapy. DESIGN: Cross-sectional study. SETTING: Urban hospital clinic. PARTICIPANTS: One hundred ninety-six consecutive HIV-infected patients taking at least 1 antiretroviral medication, awaiting a visit with their primary care provider. METHODS: Patients were interviewed while waiting for a clinic appointment and were asked to fill out a 4-part survey with questions regarding antiretroviral adherence, illicit drug use, health beliefs, and social situation. Adherence was defined as the percentage of doses taken, i.e., the number of doses taken divided by the number of doses prescribed over a 2-week interval. Univariate and multivariate logistic regressions were performed to identify factors associated with nonadherence in different patient subgroups. MAIN RESULTS: Nonadherence to antiretroviral therapy was associated with active illicit drug use (adjusted odds ratio [AOR], 2.31; 95% confidence interval [95% CI], 1.17 to 4.58), eating fewer than 2 meals per day (AOR, 3.31; 95% CI, 1.11 to 9.92), and feeling as though pressures outside of the clinic affected patient's ability to take antiretroviral medications as prescribed (AOR, 2.22; 95% CI, 0.99 to 4.97). In patients with a history of injection drug use, nonadherence to antiretroviral therapy was independently associated with eating fewer than 2 meals per day (AOR, 17.54; 95% CI, 1.92 to 160.4) and active illicit drug use (AOR, 4.18; 95% CI, 1.68 to 10.75). In patients without any injection drug use, nonadherence was only associated with feeling as though pressures outside of clinic affected patient's ability to take antiretroviral medications as prescribed (AOR, 3.55; 95% CI, 1.07 to 11.76). Male-to-male sexual contact was associated with lower nonadherence in patients with an HIV risk factor other than injection drug use (AOR, 0.35; 95% CI, 0.13 to 0.95). A history of drug use but no illicit drug use within 6 months of the interview was not associated with an increased rate of nonadherence. CONCLUSIONS: Although our sample size was limited and variables that are not significant in subgroup analysis may still be associated with adherence, our results suggest that correlates of nonadherence are HIV risk factor specific. Strategies to increase antiretroviral adherence in HIV-infected patients should include social support interventions targeted at different risk factors for different patient groups.     

HIV testing and antiretroviral treatment strategies for prevention of HIV infection: impact on antiretroviral drug resistance

'Test and treat' is a strategy in which widespread screening for human immunodeficiency virus (HIV) is followed by immediate antiretroviral therapy for those testing positive, thereby potentially reducing infectiousness in larger cohorts of infected patients. However, there is a concern that test and treat could lead to increased the levels of transmissible drug-resistant HIV, especially if viral load and/or drug resistance is not routinely monitored. Reviews of the existing literature show that up to now, even in the absence of laboratory tests, drug resistance has not created major problems in sub-Saharan Africa. Here, we discuss the current evidence for the effectiveness of a preventive test and treat approach and the challenges and implications for daily clinical practice and public health.     

An algorithm-based genotypic resistance score is associated with clinical outcome in HIV-1-infected adults on antiretroviral therapy

OBJECTIVES: The aim of this study was to evaluate the association between genotypic drug resistance and the occurrence of HIV-related diseases and death in HIV-1-infected adults on antiretroviral therapy. METHODS: We performed an observational study on patients from an out-patient clinic in a university hospital. Genotypic drug resistance analysis after virological treatment failure was performed in 141 patients receiving two or more antiretroviral drugs. All patients had follow up of at least 6 months after the resistance test. An algorithm was developed to estimate the level of genotypic drug resistance and to assign an actual resistance score (ARS) for the drugs prescribed to each patient. The patient population was divided into quartiles according to patients' ARS values. Our endpoint was the risk of developing an HIV-related disease [Centers for Disease Control and Prevention (CDC) category B or C] during the period starting 6 months prior to and ending 6 months after the genotypic resistance test, or death during the 6 months following the resistance test. RESULTS: There was a significant association between the level of resistance to the drugs prescribed (ARS) and our clinical endpoint: the odds ratio for an endpoint (with 95% confidence interval) was 3.20 (1.28-7.99), adjusted for CD4 cell count and HIV RNA, in patients in the highest ARS quartile compared with patients in the other three quartiles. CONCLUSIONS: Our study indicates that patients with high-level genotypic drug resistance are at increased risk of developing an HIV-related disease. This association could not be explained by differences in CD4 cell count or HIV RNA levels.     

Namibian prisoners describe barriers to HIV antiretroviral therapy adherence

Little is available in scholarly literature about how HIV-positive prisoners, especially in low-income countries, access antiretroviral therapy (ART) medication. We interviewed 18 prisoners at a large prison in Namibia to identify barriers to medication adherence. The lead nurse researcher was a long-standing clinic employee at the prison, which afforded her access to the population. We identified six significant barriers to adherence, including (1) the desire for privacy and anonymity in a setting where HIV is strongly stigmatized; (2) the lack of simple supports for adherence, such as availability of clocks; (3) insufficient access to food to support the toll on the body of ingesting taxing ART medications; (4) commodification of ART medication; (5) the brutality and despair in the prison setting, generally leading to discouragement and a lack of motivation to strive for optimum health; and (6) the lack of understanding about HIV, how it is transmitted, and how it is best managed. Because most prisoners eventually transition back to communitysettings when their sentences are served, investments in prison health represent important investments in public health.     

Evidence-based, multifactorial approach to addressing non-adherence to antiretroviral therapy and improving standards of care

Background: Near‐perfect adherence to antiretroviral therapy over time is critical to achieve viral suppression and recovery of functional immunity in individuals infected with HIV. The concept of adherence as a dynamic behaviour influenced by multiple biopsychosocial factors motivated us to implement an integrated, multifactorial programme in our hospital‐based setting. The aims of this study were to survey the scope and determinants of non‐adherence in patients attending the Ambulatory HIV Service at Royal Perth Hospital, to develop a method for longitudinal monitoring and to implement measures tailored to support individuals. Methods: The US Adult AIDS Clinical Trials Group self‐report baseline adherence, follow‐up and side‐effect questionnaires were used to survey 247 patients at two time‐points between September 2002 and February 2003. A longitudinal monitoring method was developed and the WA HIV Cohort Study database used to collate results with clinical markers up to December 2005. Results: Adherence was associated with viral suppression and CD4 T‐cell recovery and improved over the 3‐year period under observation (all P < 0.001). Diminishing adherence was associated with younger age (P = 0.002), substance use (P < 0.01), perceived stress (P = 0.04) and indicators of depression (P = 0.03). The analyses showed relationships between personal experience of side‐effects and the depression indicator scale in patients on antiretroviral therapy. Conclusion: The programme resulted in an improvement in adherence in our cohort even after adjusting for pill burden, dosing frequency and highly active antiretroviral therapy regimen and has enhanced focus on patients vulnerable to non‐adherence while supporting those not currently at risk.     

Relation of physician specialty and HIV/AIDS experience to choice of guideline-recommended antiretroviral therapy

BACKGROUND: Controversy exists regarding who should provide care for those with HIV/AIDS. While previous studies have found an association between physician HIV experience and patient outcomes, less is known about the relationship of physician specialty to HIV/AIDS outcomes or quality of care. OBJECTIVE: To examine the relationship between choice of appropriate antiretroviral therapy (ART) to physician specialty and HIV/AIDS experience. DESIGN: Self-administered physician survey. PARTICIPANTS: Random sample of 2,478 internal medicine (IM) and infectious disease (ID) physicians. MEASUREMENTS: Choice of guideline-recommended ART. RESULTS: Two patients with HIV disease, differing only by CD4+ count and HIV RNA load, were presented. Respondents were asked whether ART was indicated, and if so, what ART regimen they would choose. Respondents' ART choices were categorized as "recommended" or not by Department of Health and Human Services guidelines. Respondents' HIV/AIDS experience was categorized as moderate to high (MOD/HI) or none to low (NO/LO). For Case 1, 72.9% of responding physicians chose recommended ART. Recommended ART was more likely (P <.01) to be chosen by ID physicians (88.2%) than by IM physicians (57.1%). Physicians with MOD/HI experience were also more likely (P <.01) to choose recommended ART than those with NO/LO experience. Finally, choice of ART was examined using logistic regression: specialty and HIV experience were found to be independent predictors of choosing recommended ART (for ID physicians, odds ratio [OR], 4.66; 95% confidence interval [95% CI], 3.15 to 6.90; and for MOD/HI experience, OR, 2.05; 95% CI, 1.33 to 3.16). Results for Case 2 were similar. When the analysis was repeated excluding physicians who indicated they would refer the HIV "patient," specialty and HIV experience were not significant predictors of choosing recommended ART. CONCLUSIONS: Guideline-recommended ART appears to be less likely to be chosen by generalists and physicians with less HIV/AIDS experience, although many of these physicians report they would refer these patients in clinical practice. These results lend support to current recommendations for routine expert consultant input in the management of those with HIV/AIDS.