Efficacy Of Highly Active Antiretroviral Therapy Research Articles

The abnormal distribution of NK cell subsets before HAART treatment may be related to the level of immune reconstitution in HIV patient

BackgroundHIV infection leads to the damage of NK cells, which is closely associated with the disease's progression, but whether it affects immune reconstitution after Highly Active Antiretroviral Therapy (HAART) is not clear. MethodsFrom March 9 to October 31, 2017, a total of 75 confirmed cases with HIV in Wenzhou were collected and analyzed. NK cell subsets were measured and compared among three groups: the control group, the group whose CD4+ T cell counts <200/μL (named as low-CD4 group) and the group whose CD4+ T cell counts ≥200/μL (named as high-CD4 group). The lymphocytic subsets were dynamically monitored in patients with HIV after HAART. ResultsPatients in low-CD4 group have lower proportion of CD3−CD56dimCD16+ NK cell subset, but have higher proportion of CD3−CD56−CD16+ NK cell subsets, which were compared with patients in high-CD4 group (All P values <0.01). There is a positive correlation between the proportion of CD3−CD56−CD16+ NK cell subset and CD4+ T cell counts (r = 0.628, p < 0.001). Patients in the low-CD4 group have higher expression of PD-1 and PS on NK cells than patients in the high-CD4 group (All P values < 0.05). The odds ratio of the proportion of the CD3−CD56−CD16+ NK cell subset before treatment for HAART efficacy was 0.826 (p < 0.001). ConclusionsThere are abnormalities in the proportion and function of NK cell subsets in HIV patients, which are associated with disease progression. The proportion of the CD3−CD56−CD16+ NK cell subset before treatment is related with HAART efficacy.

Diffusion tensor magnetic resonance imaging of white matter integrity in patients with HIV-associated neurocognitive disorders.

BackgroundThis study investigated the efficacy and neurotoxicity of highly active antiretroviral therapy (HAART) by evaluating white matter (WM) injury using diffusion tensor magnetic resonance imaging (DTI) in patients with human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND).MethodsForty-six patients with HAND underwent DTI before and every six months during HAART treatment. DTI data, including fractional anisotropy (FA) and mean diffusivity (MD) values of structural WM before and after HAART, were compared. The relationship between DTI values and plasma viral loads was tested. MD was more sensitive than FA for evaluating WM injury in HAND-positive patients.ResultsFollowing 12 months of HAART, increased MD values (compared to 6 months of HAART) were observed in the right temporal lobe, right parietal lobe, right occipital lobe, right anterior limb of the internal capsule, right lenticular nucleus, the right cerebral peduncle, left caudate nucleus, left dorsal thalamus, and left posterior limb of the internal capsule. MD values in the left genu of the internal capsule (r=0.350, P=0.017) and left corona radiata (r=0.338, P=0.021) were positively correlated with plasma viral loads.ConclusionsDTI may be useful for assessing the efficacy and neurotoxicity of HAART in HAND-positive patients. Starting HAART may halt WM injury; however, prolonged HAART could worsen WM injury, highlighting the importance of optimal HAART duration.

A meta-analysis of the efficacy of HAART on HIV transmission and its impact on sexual risk behaviours among men who have sex with men

Evidence showed preventive impacts of the highly active antiretroviral therapy (HAART) on the Human Immunodeficiency Virus (HIV) transmission amomg heterosexual population, however, that is of deficit among men who have sex with men (MSM). The aim was to systematically examine the efficacy of HAART on HIV transmission and the association between the HAART initiation and unprotected anal intercourse (UAI) in MSM population. Three electronic databases were fully searched for articles published in peer-reviewed journals between 1996 and 2017. Of 1616 identified articles, fifteen articles were eligible for meta-analyses. The summary incidence rate (IR) of HIV was 6.63/100 person-year (95%CI 2.06–11.20/100 person-year)(p = 0.004). The pooled per-contact rate (PCR) of HIV was 0.42% (95% CI 0.21–0.63%)(p < 0.05). The HAART initiation (vs non-HAART) was not associated with engaging in UAI, with odds ratio (OR) 1.09 (95% CI 0.90–1.34)(p > 0.05). In the stratified analysis, participants with no less than 6 months recall period was slightly more likely to engage in UAI (OR 1.32; 95% CI 1.01–1.74)(p < 0.05). It indicated that HAART has potential efficacy on reducing infectivity of HIV positive individuals in anal intercourses. The relationship between the HAART initiation and UAI was not significant and may be influenced by some social-demographic factors. Consistent condom use and education on safe sex among MSM are crucial.

Diffusion Tensor MR Imaging of White Matter Integrity in Patients with HIV-Associated Neurocognitive Disorders

Background: Effective highly active antiretroviral therapy (HAART) could prevent progression of white matter (WM) injury. However, prolonged use of HAART may induce neurotoxicity. This study investigated the efficacy and neurotoxicity of HAART by evaluating WM injury using diffusion tensor magnetic resonance imaging (DTI) in patients with HIV-associated neurocognitive disorders (HAND). Methods: Forty-six patients with HAND underwent DTI before and every six months during HAART treatment. DTI data, including fractional anisotropy (FA) and mean diffusivity (MD) values of structural WM before and after HAART, were compared. The relationship between DTI values and plasma viral loads was also evaluated. Findings: MD was more sensitive than FA for evaluating WM injury in HAND-positive patients. Following 12 months of HAART, increased MD values (compared to 6 months of HAART) were observed in the right temporal lobe, right parietal lobe, right occipital lobe, right anterior limb of the internal capsule, right lenticular nucleus, right cerebral pedunculus, left caudate nucleus, left dorsal thalamus, and left posterior limb of the internal capsule. MD values in the left genu of the internal capsule (r = 0.350, P < 0.05) and left corona radiata (r = 0.338, P < 0.05) were positively correlated with plasma viral loads. Interpretation: DTI may be useful for assessing efficacy and neurotoxicity of HAART in HAND-positive patients. Initiating HAART may halt WM injury; however, prolonged HAART could worsen WM injury, highlighting the importance of optimal HAART duration. Funding: Guangxi Science and Technology Department Key Research and Development Programs, Youth Science Foundation of Guangxi Medical University and International Communication of Guangxi Medical University Graduate Education. Declaration of Interest: None. Ethical Approval: All experiments performed are endorsed by the Ethics Committee of Guangxi Medical University and complied with the Declaration of Helsinki.

Analysis on antiretroviral therapy efficacy for HIV/AIDS in Zhejiang province, 2009-2014

To analyze the efficacy of highly active antiretroviral therapy(HAART)for HIV/AIDS in Zhejiang province from 2009 to 2014. A retrospective cohort study was conducted among patients with access to HAART aged <15 years from 2009 to 2014 through descriptive epidemiological analysis on the patients' demographic characteristics, HAART efficacy. The immune recovery Kaplan-Meier curves were drawn by using baseline CD(4) T lymphocytes cell(CD(4))data. The influencing factors for virus suppression were analyzed by using logistic regression model. There were 9 594 patients with access to HAART in Zhejiang from 2009 to 2014. The' average age of the patients was 38.7 years old, the male to female ratio was 4.11∶1. Heterosexual(55.9%)and homosexual(40.0%)contacts were the main transmission routes. Baseline CD(4) count 200-349 cells/μl was found in 45.4% of the patients, the median of the CD(4) count was 221(IQR: 123-298). The median of time for CD(4) recovery in patients with baseline CD(4) count <200 cells/μl was 3.48 and 11.58 times higher than the patients with baseline CD(4) count 200-349 cells/μl and baseline CD(4) count ≥350 cells/μl. Univariate and multivariate logistic regression analyses showed that marital status, HAART regimen, treatment miss in last week and CD(4) recovery were major influencing factors for HAART efficacy. HAART had good treatment effecacy in HIV/AIDS patients in Zhejiang. The baseline CD(4) count and adherence to HAART were the most important influencing factors. It is recommended to take measures to expand HIV screening and HAART coverage, conduct HAART adherence education, and strengthen the special care for high-risk groups to improve the HAART efficacy in Zhejiang province.

HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial.

BackgroundThe phase II multicenter, randomized, open label, therapeutic trial (ISS T-002, Clinicaltrials.gov NCT00751595) was aimed at evaluating the immunogenicity and the safety of the biologically active HIV-1 Tat protein administered at 7.5 or 30 μg, given 3 or 5 times monthly, and at exploring immunological and virological disease biomarkers. The study duration was 48 weeks, however, vaccinees were followed until the last enrolled subject reached the 48 weeks.Reported are final data up to 144 weeks of follow-up. The ISS T-002 trial was conducted in 11 clinical centers in Italy on 168 HIV positive subjects under Highly Active Antiretroviral Therapy (HAART), anti-Tat Antibody (Ab) negative at baseline, with plasma viremia <50 copies/mL in the last 6 months prior to enrollment, and CD4+ T-cell number ≥200 cells/μL. Subjects from a parallel observational study (ISS OBS T-002, Clinicaltrials.gov NCT0102455) enrolled at the same clinical sites with the same criteria constituted an external reference group to explore biomarkers of disease.ResultsThe vaccine was safe and well tolerated and induced anti-Tat Abs in most patients (79%), with the highest frequency and durability in the Tat 30 μg groups (89%) particularly when given 3 times (92%). Vaccination promoted a durable and significant restoration of T, B, natural killer (NK) cells, and CD4+ and CD8+ central memory subsets. Moreover, a significant reduction of blood proviral DNA was seen after week 72, particularly under PI-based regimens and with Tat 30 μg given 3 times (30 μg, 3x), reaching a predicted 70% decay after 3 years from vaccination with a half-life of 88 weeks. This decay was significantly associated with anti-Tat IgM and IgG Abs and neutralization of Tat-mediated entry of oligomeric Env in dendritic cells, which predicted HIV-1 DNA decay. Finally, the 30 μg, 3x group was the only one showing significant increases of NK cells and CD38+HLA-DR+/CD8+ T cells, a phenotype associated with increased killing activity in elite controllers.ConclusionsAnti-Tat immune responses are needed to restore immune homeostasis and effective anti-viral responses capable of attacking the virus reservoir. Thus, Tat immunization represents a promising pathogenesis-driven intervention to intensify HAART efficacy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-015-0151-y) contains supplementary material, which is available to authorized users.

Efficacy and side effects of HAART in HIV-infected patients with different CD4 cell counts

Objective To explore the efficacy and side effects of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients with different CD4+ cell counts. Methods The clinical data of HIV-infected patients who accepted TDF (tenofovir disoproxil fumarate) + 3TC (lamivudine) + EFV (efavirenz) treatment were retrospectively collected in Jiangmen region. All patients were divided into group A(350/μl ≤ CD4+ < 500/μl), group B (200/μl ≤ CD4+ < 350/μl) and group C(CD4+ < 200/μl)according to their CD4+ cell counts. The efficacy and side effects in different groups were compared. Results A total of 132 clinical cases was collected, including 32 cases in group A, 42 cases in group B, and 58 cases in group C. No statistically difference was found among three groups in terms of gender, age, or route of transmission. CD4+ cell counts after treatment was significantly higher than that before treatment in each group (P 0.05). The incidence of side effects in groups A, B, and C was 4/32, 14/42, and 32/58 in 3-month HAART, respectively; and 1/32, 8/42, and 22/58 in 3~12 month HAART, respectively. Statistical analysis showed significant difference among three groups (group C > group B > group A, P<0.05). Conclusions It was effective to begin the anti-retroviral treatment in all stages. The incidence of side effects may be less if anti-retroviral treatment began in early period. Key words: CD4 lymphocyte count; HIV infections/drug therapy; Antiviral agents/adverse effects; Retrospective studies

Prevalence of and risk factors for pulmonary abnormalities in HIV‐infected patients treated with antiretroviral therapy

Pulmonary abnormalities are often present in patients infected with the human immunodeficiency virus (HIV). The aim of the study was to determine the prevalence and characteristics of, and risk factors for, pulmonary abnormalities in HIV-positive patients. A total of 275 HIV-positive patients [mean (± standard deviation) age 48.5 ± 6.6 years] were included in the study, of whom 95.6% had been receiving highly active antiretroviral therapy (HAART) for a mean (± standard deviation) duration of 11.9 ± 5.4 years. The median (interquartile range) CD4 lymphocyte count was 541 (392-813) cells/μL, and 92% of the patients had an undetectable viral load. We determined: (1) spirometry, static lung volumes, lung diffusing capacity, pulmonary gas exchange and exercise tolerance, and (2) the amount of emphysema via a computed tomography (CT) scan. Chronic cough and expectoration (47%) and breathlessness during exercise (33.9%) were commonly reported. Airflow limitation (AL) was present in 17.2%, low pulmonary diffusing capacity in 52.2% and emphysema in 10.5-37.7% of patients, depending on the method used for quantification. Most of these abnormalities had not been diagnosed or treated previously. Smoking exposure and previous tuberculosis were the main risk factors for AL, whereas smoking exposure and several variables related to HIV infection appeared to contribute to the risk of emphysema and low diffusing capacity. Despite HAART, pulmonary structural and functional abnormalities are frequent in HIV-positive patients. They are probably attributable to both environmental (smoking and tuberculosis) and HIV-related factors. Most of these abnormalities remain unnoticed and untreated. Given the relatively young age of these patients, these results anticipate a significant health problem in the next few years as, thanks to the efficacy of HAART, patients survive longer and experience the effects of aging.

Assessing the effectiveness of antiretroviral regimens in cohort studies involving HIV-positive injection drug users

We compared the effectiveness of different highly active antiretroviral therapy (HAART) regimens considering, separately, history of injection drug use (IDU) (yes/no). DESIGN, METHODS: A total of 1163 HIV-infected patients initiated HAART between 1 January 2000 and 28 February 2009 in British Columbia, Canada, and were followed until 28 February 2010. HAART effectiveness was measured by the ability to achieve viral suppression below 50 copies/ml at 6 months. We compared HAART regimens containing efavirenz and boosted atazanavir. We developed logistic regression models using different techniques to control for potential confounders. Among the 1163 patients, 796 (68%) achieved viral suppression at 6 months (32% reporting a history of IDU). Different confounding models yielded very similar odds ratios for achieving viral suppression. Boosted atazanavir-based HAART demonstrated to be the most effective regimen, showing a surprisingly higher benefit for patients with a history of IDU (odds ratios from different models ranged from 1.74-1.95 to 1.45-1.51). The literature has conflicting results regarding the effectiveness of HAART to treat HIV infection among those with a history of IDU. We have shown that most patients, with and without a history of IDU, were able to achieve viral suppression at 6 months. Boosted atazanavir-based HAART was the most resilient regimen and it was more effective than efavirenz-based HAART among IDUs. Given the limited inclusion of IDU in clinical trials of HAART's efficacy, a randomized clinical trial comparing different first-line HAART regimens among IDU is warranted based on these results.

Efficacy of Antiretroviral Therapy Switch in HIV-Infected Patients: A 10-Year Analysis of the EuResist Cohort

Introduction: Highly active antiretroviral therapy (HAART) has been shown to be effective in many recent trials. However, there is limited data on time trends of HAART efficacy after treatment change. Methods: Data from different European cohorts were compiled within the EuResist Project. The efficacy of HAART defined by suppression of viral replication at 24 weeks after therapy switch was analyzed considering previous treatment modifications from 1999 to 2008. Results: Altogether, 12,323 treatment change episodes in 7,342 patients were included in the analysis. In 1999, HAART after treatment switch was effective in 38.0% of the patients who had previously undergone 1–5 therapies. This figure rose to 85.0% in 2008. In patients with more than 5 previous therapies, efficacy rose from 23.9 to 76.2% in the same time period. In patients with detectable viral load at therapy switch, the efficacy rose from 23.3 to 66.7% with 1–5 previous treatments and from 14.4 to 55.6% with more than 5 previous treatments. Conclusion: The results of this large cohort show that the outcome of HAART switch has improved considerably over the last years. This result was particularly observed in the context after viral rebound. Thus, changing HAART is no longer associated with a high risk of treatment failure.

Rapid Turnover of 2-LTR HIV-1 DNA during Early Stage of Highly Active Antiretroviral Therapy

BackgroundDespite prolonged treatment with highly active antiretroviral therapy (HAART), the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment.Methodology/Principal FindingsIn this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS) levels did not reveal any significant changes in the same treatment period.Conclusions/SignificanceOur study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.

Clinical manifestations of treatment-naive patients with acquired immunodeficiency syndrome and responses to highly active antiretroviral therapy in the Taipei Veterans General Hospital: A 5-year prospective study

Taipei Veterans General Hospital, one of the medical centers in Taiwan, has provided highly active antiretroviral therapy (HAART) to human immunodeficiency virus/AIDS patients for more than 10 years. Five years ago, we began a prospective follow-up of our patients' clinical manifestations and responses to HAART by collecting their clinical data. In this study, we analyzed the morbidity, mortality, and responses to HAART of treatment-naive AIDS patients. The purpose was to provide local data that may be valuable in Taiwan. Study cases were enrolled from January 1, 2004, to February 28, 2009, with inclusion criteria of newly diagnosed AIDS during hospitalization and being naive to HAART. Antiretroviral therapy was initiated. To evaluate the clinical responses to HAART, we excluded patients who were pregnant, died within 1 month after confirmation of an AIDS diagnosis, failed to initiate HAART, or were lost to follow-up for more than 6 months. Plasma viral loads and CD4(+) counts were quantified by reverse-transcriptase polymerase chain reaction and flow cytometry, respectively. Statistical analysis was performed using SPSS statistical software. A total of 49 patients were enrolled and 45 patients fulfilled the inclusion criteria for evaluating the efficacy of HAART. At 3 months, 12 months, and 30 months after the initiation of HAART, 64.4% (29 of 45), 88.2% (30 of 34), and 93.8% (15 of 16) had undetectable plasma viral loads, respectively, and 37.8% (17 of 45), 73.5% (25 of 34), and 81.2% (13 of 16) had CD4(+) counts of more than 200 cells/μL, respectively. Median CD4(+) counts increased from baseline at Month 3 by 171 cells/μL and at Month 30 by 375 cells/μL. The overall mortality was 22.4% (11 of 49). The virologic and immunologic responses after initiating HAART in this study demonstrated our achievements in providing care and treatment for AIDS patients during this 5-year period, which provides a strong evidence of the efficacy of HAART.

Virologic outcomes of HAART with concurrent use of cytochrome P450 enzyme-inducing antiepileptics: a retrospective case control study

BackgroundTo evaluate the efficacy of highly-active antiretroviral therapy (HAART) in individuals taking cytochrome P450 enzyme-inducing antiepileptics (EI-EADs), we evaluated the virologic response to HAART with or without concurrent antiepileptic use.MethodsParticipants in the US Military HIV Natural History Study were included if taking HAART for ≥6 months with concurrent use of EI-AEDs phenytoin, carbamazepine, or phenobarbital for ≥28 days. Virologic outcomes were compared to HAART-treated participants taking AEDs that are not CYP450 enzyme-inducing (NEI-AED group) as well as to a matched group of individuals not taking AEDs (non-AED group). For participants with multiple HAART regimens with AED overlap, the first 3 overlaps were studied.ResultsEI-AED participants (n = 19) had greater virologic failure (62.5%) compared to NEI-AED participants (n = 85; 26.7%) for the first HAART/AED overlap period (OR 4.58 [1.47-14.25]; P = 0.009). Analysis of multiple overlap periods yielded consistent results (OR 4.29 [1.51-12.21]; P = 0.006). Virologic failure was also greater in the EI-AED versus NEI-AED group with multiple HAART/AED overlaps when adjusted for both year of and viral load at HAART initiation (OR 4.19 [1.54-11.44]; P = 0.005). Compared to the non-AED group (n = 190), EI-AED participants had greater virologic failure (62.5% vs. 42.5%; P = 0.134), however this result was only significant when adjusted for viral load at HAART initiation (OR 4.30 [1.02-18.07]; P = 0.046).ConclusionsConsistent with data from pharmacokinetic studies demonstrating that EI-AED use may result in subtherapeutic levels of HAART, EI-AED use is associated with greater risk of virologic failure compared to NEI-AEDs when co-administered with HAART. Concurrent use of EI-AEDs and HAART should be avoided when possible.

Prevalence of anaemia and immunological markers among Ghanaian HAART-naïve HIV-patients and those on HAART

Highly active antiretroviral therapy (HAART) for people living with HIV/AIDS (PLWHA) has been generally accepted as the gold standard for the management of HIV patients but conflicting reports about the ability of HAART to improve upon the quality of life of HIV patients has cast doubts over the efficacy and the need for therapy. This study was conducted to assess the efficacy and ability of HAART to resolve immunological and haematological abnormalities in HIV infected patients, existent sex variations in immunological and haematological parameters and CD4 predictive ability of the study parameters. A total of 442 PLWHA consisting of 166 patients on HAART (28 males and 138 females) and 276 HAART-naïve patients (76 males and 200 females) were recruited for this study. Complete haemogram, immunological analysis (CD4 & CD3) and weight were measured for all the patients. HAART patients were older and heavier than their naïve counterparts. The incidence of anaemia (Hb less or equal to 10.5 (63%) and PCV < 30% (37.6%)) and lymphopoenia (16.7%) in HAART-naïve patients was significantly higher compared to their counterparts on HAART (46%, 15.2% and 5.3%) respectively. 70% of HAART-naïve females had anaemia in comparison to 44% in HAART-naïve males (P = 0.0001). The likelihood of developing microcytic hypochromic anaemia in HAART-naïve patients was 5 times more compared to those on HAART (P = 0.0002). Total lymphocyte count, haemoglobin, lymphocyte count and weight were significant predictors of CD4 counts and TLC values between 1.0 - 2.0 k µL(-1) was a significant predictor of CD4 <200 cells mm(-3). HAART has the capability of reducing the incidence of anaemia and lymphopoenia which are associated with disease progression and death in HIV infected patients. Total lymphocyte count, haemoglobin and weight could also serve as useful predictive tools in the management and monitoring of HIV infected patients in resource limited settings.

Identification of a novel Vpr-binding compound that inhibits HIV-1 multiplication in macrophages by chemical array

Although HIV-1 replication can be controlled by highly active anti-retroviral therapy (HAART) using protease and reverse transcriptase inhibitors, the development of multidrug-resistant viruses compromises the efficacy of HAART. Thus, it is necessary to develop new drugs with novel targets. To identify new anti-HIV-1 compounds, recombinant Vpr was purified from transfected COS-7 cells and used to screen compounds by chemical array to identify those that bound Vpr. From this screen, 108 compounds were selected as positive for Vpr binding. Among these, one structurally similar group of four compounds showed anti-HIV activity in macrophages. In particular, compound SIP-1 had high inhibition activity and reduced the levels of p24 by more than 98% in macrophages after 8 or 12days of infection. SIP-1 had no cytotoxic effects and did not disrupt cell cycle progression or induce apoptosis of Molt-4 and HeLa cell lines as measured by MTT assay, flow-cytometry analysis, and a caspase-3 assay. In addition, SIP-1 specifically bound to Vpr as assessed by photo-cross-linked small-molecule affinity beads. These results suggest that Vpr is a good target for the development of compounds that could potentially inhibit HIV-1 replication. Collectively, our results strongly suggest that chemical array is a useful method for screening anti-viral compounds.

Epidemiology of Antiretroviral Multiclass Resistance

Given the recent evolution of therapeutic trends, the frequency and determinants of multiclass-resistant HIV infection in the modern combination highly active antiretroviral therapy (HAART) era are less well understood. In this study, the authors characterize the epidemiology of antiretroviral multiclass resistance among HAART-naïve patients enrolled in a province-wide HAART distribution program in British Columbia, Canada. HAART and resistance testing are free to eligible individuals in British Columbia. This study was based on patients who initiated naïve on HAART and were followed during January 1, 2000-June 30, 2007. Explanatory logistic and survival models were built to identify those factors most influential in the emergence of multiclass resistance. Among the 1,820 individuals in our study, 833 (46%) were tested for antiretroviral resistance at least once during their follow-up. Multiclass resistance was observed in 142 individuals (n = 833; 17%) during a median follow-up of 14 months (interquartile range, 3-34 months) (incidence rate, 0.8 cases/1,000 person-months). The authors found that initial nonnucleoside reverse transcriptase inhibitor-based HAART was the main determinant of multiclass resistance. Given that these inhibitors are still widely used, priority should be given to make resistance testing and viral load monitoring a standard part of human immunodeficiency virus care to maximize the long-term efficacy and efficiency of HAART.

HIV infection in the era of cytomics

INTRODUCTION: THE DIMENSIONS OF THE PROBLEM The human immunodeficiency virus (HIV) has caused one of the most dramatic epidemics of the twentieth century, which is continuing with the same strength in the new millennium (http://www.unaids.org). The infection has spread worldwide, leaving no region of the world unaffected, and, even after almost 30 years from the description of the first cases (1), still represents a major challenge for human health. Until 1996, the infection with HIV caused an inexorable and catastrophic decline in the quality of immune responses and ultimately in the patient’s health, until death was a welcomed relief. Then, effective drugs, collectively defined as HAART (highly active antiretroviral therapy) were designed and developed that are actually able to keep the infection dormant for extremely long periods (2). However, the virus cannot be eradicated from patients, and always gives signs of its presence. A relevant number of infected people cannot afford treatment for economical reasons, and the failure of several public health programs and of many therapy projects are even too evident. As a consequence, millions of HIV1 people worldwide are not treated or do not receive a correct treatment, considering that drugs have to be taken according to the indications provided by the quantification of plasmatic viral load and CD41 T cell count and/or percentage. Thus, patients often perish without any specific intervention, without knowing which disease is affecting them and what could have been done to protect and improve their health, if not to prevent the infection. Those who can assume HAARToften develop serious side effects, and viral resistance to drugs can develop for a high percentage of patients. Both these phenomena can lead to a suboptimal (if not bad) assumption of therapies, further favoring the epidemics. Finally, the efficacy of HAART has paradoxically resulted in a relaxation of appropriate public and private health measures that threaten a recrudescence of the epidemics. In such a scenario, heavily influenced by economical and political interests, the community of scientists has always been working with unprecedented efforts and devotion to the cause.

Patients and family care givers' experiences around highly active antiretroviral therapy (HAART)

Even with advances in the medical management of HIV/AIDS, it remains an important cause of morbidity and mortality. Network members are a source of support and may be designated as the patient's surrogate therapeutic decision maker. However, little is known about the role of caregivers regarding highly active antiretroviral therapy (HAART) and adherence to medication, especially among low income and medically underserved HIV-infected individuals. The objective of this analysis was to explore patients and their caregivers' understanding, insight, and perceptions of HAART. This was a qualitative study conducted in an urban teaching hospital in the Bronx, NY, consisting of 144 adults with advanced HIV/AIDS and their informal/familial caregivers. Patients and caregivers completed in-depth interviews and brief questionnaires. The data were analyzed using standard qualitative techniques. Themes related to HAART efficacy, side effects, and adherence were identified in the discussions with both patients and their care providers. Looking for consistencies and discordant reports of patients–caregivers dyadic experience with HAART and their association with healthcare sentiment, it was found that the accounts of both members of the dyad were more likely to reflect positive feelings about the patient's healthcare experience when they shared perceptions about the treatment, and were more likely to have a negative viewpoint when the dyad was discordant about treatment. These findings support the importance for HIV healthcare providers to include both patients and their caregivers in discussions about HAART, in order to improve their understanding of and satisfaction with the medication, and, to ultimately contribute to patients' adherence. The study also suggests that healthcare teams may enhance dialog with patients and caregivers to create therapeutic decisions to accommodate the priorities and values of the patient and their family. Clinical, educational, and evaluating tools need to be further developed and evaluation to facilitate this process.

Empfehlungen zum leitliniengerechten Einsatz der HIV-Resistenztestung

Guidelines for application of HIV drug resistance testing have recently been develeped in Europe and the USA. This article discusses these recommendations. Since the widespread use of highly active antiretroviral therapy (HAART), quality of life has been improved for the majority of HIV-infected patients and the mortality rate has declined significantly. However, an incomplete suppression of viral replication results in selection of resistant viral strains resulting in a loss of HAART efficacy and worsening in the quality of life. Resistance testing is likely to improve virological monitoring of untreated but especially in pre-treated patients. Genotypical and phenotypical assays present similar results, but genotypical testing is the method of choice initially. Translation of resistance testing into clinical decisions-making requires consideration of a patient's history, interpretation of results by a validated algorithm, and expert advice. Problems of adherence should be avoided by counselling and therapeutic drug monitoring. Resistance testing or storage of a patient's plasma sample should be undertaken as early as possible in the disease history. If this is not possible, treatment with HAART, including a boosted protease inhibitor, is warranted. European and USA guidelines present similar recommendations. HIV drug resistance is preventable by rational choice of drug combinations in HAART. After development of resistance-associated mutations, drug resistance testing can preserve future treatment options and preventing further clinical deterioration. The method has been incorporated into national and international guidelines on the basis of good scientific evidence.

Considering childbearing in the age of highly active antiretroviral therapy (HAART): Views of HIV-positive couples

Objectives: Based on a qualitative study conducted in Bulawayo, Zimbabwe, this article examines how the availability of HAART since April 2004 may impact the views and choices of HIV-positive couples on childbearing. Methods: In-depth interviews were conducted with 15 couples where at least one partner was HIV positive. All respondents were of reproductive age and had or were confronting reproductive and sexual decision-making. Results: HAART seems to have had a profound impact on the subject of childbearing among those who still desire to have children. Where hitherto individuals had only a desire for a child many are now, as a result of the availability of HAART, actively planning to have one. HAART has not only transformed their physical state but it has also transformed mostly what had been desire into intention. The impact, however, has not been uniform. Some respondents still desired to have a child but were not yet convinced about the efficacy of HAART in preventing vertical transmission. Some respondents felt that HAART may have a negative impact on the foetus and as such were against childbearing by HIV-positive people. No respondent indicated that their desire or intention to have a child had been extinguished by the advent of HAART. Conclusion: Based on the findings of the study, HAART seems to have had a differential but nonetheless significant role in the reproductive plans of HIV-positive couples. The study also notes that there is a need to make available complete and unbiased information on HAART, mother-to-child transmission risk (MTCT) and pregnancy to HIV-positive couples so as to enable them to make informed decisions.