Early Initiation Of Highly Active Antiretroviral Therapy Research Articles

Long-term prognosis and overall mortality in patients with progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis.

2311. Long-term prognosis and risk factors for overall mortality in patients with progressive multifocal leukoencephalopathy

Abstract Background Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of JC virus, almost in patients with immunosuppressive conditions. PML is a fatal infection with a reported 3-month mortality rate of 30–50% and a 2-month mortality rate of up to 90% in the non-human immunodeficiency virus (HIV) population. Despite high mortality, studies on PML are still lacking due to its low prevalence and incidence. Therefore, this study aimed to figure out long-term prognosis of PML and prognostic factors for mortality through a long observation period. Methods We retrospectively reviewed 68 PML patients with admitted to two tertiary hospitals in South Korea from 1999 to 2021. A total of 47 PML patients were finally enrolled after exclusion. The primary endpoint was long-term overall mortality. For survival analysis, Kaplan-Meier curve and Cox proportional hazards model were used. Each patient was followed up until death or until the end of the study period, whichever came first. Results The median follow-up duration was 20 (interquartile range [IQR], 3–79) months. The median age was 46 years, 27 (57.4%) were diagnosed with HIV, 19 (40.4%) were using immunosuppressive drugs. The median last follow-up modified Rankin Scale (mRS) was higher in non-HIV PML patients group (5 [IQR, 4–6] vs 4 [IQR, 2–5], p=0.020). The median survival duration was 184 (IQR 74–1,566) days in the non-HIV group and 1,564 (IQR 254–3,444) days in the HIV group. The overall mortality rate of PML patients was significantly higher in non-HIV group (80.0% vs 40.7%, p=0.007), also confirmed by the Kaplan-Meier curve and log-rank test (p=0.007). Initial mRS (HR 1.685, 95% CI: 1.028–2.762, p=0.038), HIV patients with highly active antiretroviral therapy (HAART) (HR 0.374, 95% CI: 0.172–0.815, p=0.013) had a significant effect on overall mortality. Conclusion With the widespread adoption of HAART, the survival duration of HIV patients with PML has been extended, but the mortality rate is still high. Also, the prognosis for PML in non-HIV patients is still frustrated. Initial mRS is a significant risk factor for long-term overall mortality in PML patients. Early detection of PML and early initiation of HAART in HIV patients may improve the patient's prognosis. Disclosures All Authors: No reported disclosures.

Analysis of the Influencing Factors of Immunological Nonresponders in Wuhan, China.

Objective CD4+ cell recovery is hampered in some human immunodeficiency virus (HIV)-infected patients, despite a successful highly active antiretroviral therapy (HAART) with suppressed viral replication. We investigated the factors that might have hindered the CD4+ cell recovery in these patients. Methods In this retrospective study, we collected the data of all immune nonresponders (INRs) in Wuhan, China, until the end of 2020. A linear model was constructed based on the data from 220 patients with baseline and follow-up records. The response variables in this study were the CD4+ cell count increase. The predictor variables considered in this study were those factors likely to affect the CD4+ cell recovery. Results Our findings revealed that the plasma HIV-1 viral load of all patients was suppressed and 87.3% patients' CD4+ cells was increased after more than one year of the HAART treatment. In addition, their last follow-up showed a significant reduction in complications. In our results, the body mass index (BMI), number of months since HIV diagnosis to HAART start, and nonuse of co-trimoxazole were negatively correlated with the increase in CD4+ cells (P < 0.05). However, there were positive associations between serum creatinine levels and CD4+ cell recovery (P < 0.05). Further stratified analyses indicated that the associations between HAART replacement or creatinine usage and CD4+ cell growth were only observed in those participants with a BMI <18.5 (P < 0.05). Conclusions An early initiation of HAART and co-trimoxazole preventive therapy (CPT) can promote immune reconstitution. BMI and serum creatinine can serve as monitoring indicators of immune reconstitution prognosis after the HAART.

Immuno-virological status and its associated factors among HIV-positive patients receiving highly active antiretroviral therapy at delgi primary hospital, northwest Ethiopia, 2020/2021: A cross-sectional study

BackgroundHighly active antiretroviral therapy (HAART) improves clinical outcomes by suppressing viral replication and allowing immune reconstitution. It also reduces HIV-related complications including morbidity, mortality, and extended hospitalizations for HIV-positive individuals. Regular assessment for antiretroviral treatment response is fundamentally important to address the factors associated with the poor clinical outcome including immunologic failures among HIV-positive patients on HAART. Therefore, this study aimed to investigate the immuno-virological status and describe its determinants among HIV-positive patients receiving HAART at Delgi primary hospital, Northwest Ethiopia. MethodsA hospital-based cross-sectional study was conducted at Delgi primary hospital from October 25th through June 19th 2021 among a total of 442 study participants. A systematic random sampling technique was employed to enrol participants in the study. Socio-demographic and clinically related data were collected using a semi-structured questionnaire. About 3–5 ml of venous blood was collected aseptically for CD4+ T cell count and viral load test. SPSS version 20 software was used for statistical analysis. Bivariate and multivariate logistic regression analyses were conducted to determine the factors associated with immuno-virologic status among HIV-positive patients on HAART. The odds ratio with 95% CI was computed to determine the strength of association. Then, a p-value < 0.05 was considered a statistically significant association. For this study, the results were presented by using frequency summary tables, and texts. ResultsAmong the total study participants, 283 (64%) were males and the mean age of the study participants was 37 ± 11.5. The overall immunological and virological failure among highly active antiretroviral therapy (HAART) receiving participants was found to be 9.5% (42/442, 95%CI:3.23–15.09) and 12.2% (54/442, 95% CI: 2.81–23.04) respectively. In the multivariate analysis, study participants with age ≥50 years old [AOR = 1.97, p = 0.01, 95%CI (0.02–4.03)], participants having current viral load count greater ≥1000 copies/ml [AOR = 3.97, p = 0.03, 95%CI (1.09–5.01)] and having TB-co-infection [AOR = 2.51, p = 0.05, 95%CI (1.02–7.51)] were statistically associated with increased risk of immunological failure. Similarly, TB-coinfected participants were 1.88 (95%CI = 0.89–10.02) times at greater risk for virological failure. ConclusionIn this study, the magnitude of immuno-virological failure is alarming. This may be shown the need for integrated and substantial commitment to enhancing patient antiretroviral treatment adherence in the study area. Also, regular assessment for antiretroviral treatment response is fundamentally important to address the determinants associated with virological and immunologic failures among HIV-positive patients taking HAART. Furthermore, early initiation of HAART may be imperative to achieve favourable virological suppression and immunological reconstitution.

Clinical Oral Condition Analysis and the Influence of Highly Active Antiretroviral Therapy on Human Salivary Microbial Community Diversity in HIV-Infected/AIDS Patients.

The purpose of this study was to assess the clinical oral status and investigate the effect of highly active antiretroviral therapy (HAART) on oral flora diversity in human immunodeficiency virus (HIV)-infected/acquired immune deficiency syndrome (AIDS) patients. We first recorded and analyzed the demographic indicators of 108 HIV-infected patients and assessed their periodontal health, dental health and oral lesion status by oral examination. Besides, we compared the changes in salivary microbial communities of healthy controls, before and after treatment of HAART-processed AIDS patients by Roche 454 sequencing and RT-qPCR. In HIV-infected/AIDS patients, age, sex, marital status, income level, smoking and oral health behaviors had an effect on periodontal clinical indicators; age and marital status were correlated with dental clinical indicators; most of them were accompanied by oral manifestations, mainly including candidiasis albicans, salivary gland disease, AIDS-associated periodontitis, and oral ulcers. Besides, a total of 487 species were detected in the saliva of AIDS patients. The microbial communities of HAART-unprocessed AIDS patients significantly differed from those processed patients, with 112 unique microbial species. More importantly, a large number of conditioned pathogens were also detected in the saliva samples of AIDS patients, which may be associated with opportunistic infections. Therefore, HAART might have a crucial role in salivary microecological balance in AIDS patients. And these patients should pay attention to the maintenance of oral health, and the early initiation of HAART may be important for the development of oral lesions.

Immunological status and virological suppression among HIV-infected adults on highly active antiretroviral therapy

BackgroundWorld Health Organization (WHO) recommends that viral load ([VL) is a primary tool that clinicians and researchers have used to monitor patients on antiretroviral therapy (ART), an antiviral drug against retroviruses. Whereas, CD4 cell counts can only be used to monitor clinical response to ART in the absence of VL testing service. Therefore, this study is aimed to assess the level of immunological status and virological suppression, and identify associated factors among human immunodeficiency virus ([HIV)-infected adults who were taking antiretroviral drugs of combination regimen know as highly active antiretroviral therapy (HAART).MethodsA hospital-based cross-sectional study was conducted at the University of Gondar comprehensive specialized referral hospital from February to April 2018. A total of 323 adult participants on HAART were selected using a systematic random sampling technique and enrolled into the study. Blood samples for viral load determination and CD4 cell count were collected. Binary logistic regression analysis was used to determine factors associated with immunologic status and virological suppression in HIV patients on HAART. Odds ratio with 95% CI was used to measure the strength of association.ResultsVirological suppression (VL level < 1000 copies/ml) was found in 82% (95% CI 77.7, 86.1) of study participants, and it has been associated with CD4 cell count between 350 and 499 cells/mm3 (adjusted odds ratio (AOR) = 2.56; 95% CI 1.14, 5.75) and > 499 cells/mm3 (AOR = 7.71; 95% CI 3.48, 17.09) at VL testing and current age > 45 years old (AOR = 5.99; 95% CI 2.12, 16.91). Similarly, favorable immunological status (≥ 400 cells/mm3 for male and ≥ 466 cells/mm3 for female) was observed in 52.9% (95% CI 47.4, 58.8) of the study participants. Baseline CD4 cell count of > 200 cells/mm3, age at enrollment of 26 through 40 years old, and urban residence were significantly associated with favorable immunological status.ConclusionThough the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.

The predictive role of CD4+ cell count and CD4/CD8 ratio in immune reconstitution outcome among HIV/AIDS patients receiving antiretroviral therapy: an eight-year observation in China

BackgroundThe immune reconstitution after initiation of highly active antiretroviral therapy (HAART) among HIV-infected individuals substantially affects patients’ prognosis. However, the dynamic characteristics and predictors of reconstitution outcome remain unclear.MethodsIn this study, the HIV/AIDS patients with sustained virological suppression (viral load < 50 copies/ml) after HAART were enrolled. The patients were subgrouped into immunological non-responders (INRs) (< 200 cells/μl), immunological inadequate responders (IIRs) (200 ~ 500 cells/μl) and immunological responders (IRs) (> 500 cells/μl) according to the CD4 cell count after two-year HAART. The immune reconstitution data based on the CD4+ and CD8+ cell counts with 8-year follow-up were collected for analysis.ResultsThe CD4+ cell counts in the immunological responders (IRs) were significantly higher than in the immunological non-responders (INRs) and immunological inadequate responders (IIRs) (P < 0.001). The overall CD4+ cell count and CD4/CD8 ratio in the IRs increased faster than the IIRs and INRs. The CD4+ cell count growth at 0.5 year and 1 year after HAART in the IRs was significantly higher than the IIRs and INRs. The ROC curve demonstrated that 1 year CD4+ cell count had the highest predictive value, with the best cut-off value of 188 cells/μl, the predictive sensitivity was 81.0%, the predictive specificity was 85.2%, false positive rate was 14.8%, false negative rate was 19.0%, positive predictive value (IR) was 63.0%, negative predictive value (INR) was 93.5%.ConclusionsTaken together, our findings suggest that early initiation of HAART can reduce the immune reconstitution failure. The combination of baseline CD4+ cell count and baseline CD4/CD8 ratio may serve as a valid predictor of immune reconstitution prognosis after HAART.

Prevalence of human immunodeficiency virus — hepatitis B virus co-infection amongst adult patients in Mahalapye, Ngami, Serowe, Botswana: a descriptive cross-sectional study

Background: About 37 million people are living with human-immunodeficiency-virus (HIV) worldwide, with 2.6 million co-infected with the hepatitis B virus (HBV). HBV infection causes 650 000 deaths annually worldwide. Botswana has a high prevalence of HIV and a growing population of patients on highly active antiretroviral therapy (HAART). This study aimed to determine the prevalence of HIV–HBV co-infection amongst HAART eligible adult patients in some rural settings in Botswana.&#x0D; &#x0D; Methods: A cross-sectional study was conducted amongst HAART eligible adult patients at 15 HAART clinics in the Mahalapye, Ngami and Serowe Health Districts of Botswana, from August to October 2015. A total of 132 were recruited; of these 118 consented and were tested for HBsAg reactivity using Elisa.&#x0D; &#x0D; Results: Six (5.1%, 6/118) patients from the three rural health districts were HIV–HBV co-infected, with three in the 20–29 age group. The association between sex and HIV–HBV co-infection status was not statistically significant; p = 1.00. &#x0D; &#x0D; Conclusion: The finding of 5.1% HIV–HBV co-infection prevalence in some rural settings of Botswana was similar to results from one study conducted in a Botswana urban centre, while another previous similar study reported prevalence as being twice as high. This finding may call for prioritisation of pre-HAART HBV screening and early HAART initiation for all HIV-infected patients. &#x0D; &#x0D; (Full text of the research articles are available online at www.medpharm.tandfonline.com/ojfp)&#x0D; &#x0D; S Afr Fam Pract 2017; DOI: 10.1080/20786190.2016.1272230

Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era

Cognitive impairment still occurs in a substantial subset of HIV-infected patients, despite effective viral suppression with highly active antiretroviral therapy (HAART). Structural brain changes may provide clues about the underlying pathophysiology. This study provides a detailed spatial characterization of the pattern and extent of brain volume changes associated with HIV and relates these brain measures to cognitive ability and clinical variables. Multiple novel neuroimaging techniques (deformation-based morphometry, voxel-based morphometry, and cortical modeling) were used to assess regional brain volumes in 125 HIV-infected patients and 62 HIV-uninfected individuals. Ninety percent of the HIV-infected patients were on stable HAART with most of them (75%) having plasma viral suppression. Brain volumetrics and cortical thickness estimates were compared between the HIV-infected and uninfected groups, and the relationships between these measures of brain volume and indices of current and past infection severity, central nervous system penetration of HAART, and cognitive performance were assessed. Regionally specific patterns of reduced thalamic and brainstem volumes and reduced cortical thickness in the orbitofrontal cortex, cingulate gyrus, primary motor and sensory cortex, temporal, and frontal lobes were seen in HIV-infected patients compared to HIV-uninfected participants. Observed white matter loss and subcortical atrophy were associated with lower nadir CD4 cell counts, while reduction in cortical thickness was related to worse cognitive performance. Our findings suggest that distinct mechanisms may underlie cortical and subcortical injury in people with HIV and argues for the potential importance of early initiation of HAART to protect long-term brain health.

Timing of Antiretroviral Treatment, Immunovirologic Status, and TB Risk: Implications for Testing and Treatment.

Tuberculosis (TB) risk and mortality increase in the 6 months after highly active antiretroviral therapy (HAART) initiation. This short-term risk may be a consequence of HAART initiation and immune reconstitution. Alternatively, it may be due to confounding by low CD4 counts and high HIV viral loads (VLs). We assessed the TB risk before and after HAART initiation while appropriately controlling for time-updated laboratory values and HAART exposure. We conducted an observational cohort study among persons enrolled in the North American AIDS Cohort Collaboration on Research and Design from 1998 through 2011. A marginal structural model was constructed to estimate the association of HAART initiation and TB risk. Inverse probability weights for the probability of HAART initiation were incorporated. Among 26,342 patients, 94 cases of TB were diagnosed during 147,557 person-years (p-y) of follow-up. The unadjusted TB rates were 93/100,000 p-y [95% confidence interval (CI): 63 to 132] before HAART initiation, 203/100,000 p-y (95% CI: 126 to 311) ≤6 months after HAART initiation, and 40/100,000 p-y (95% CI: 29 to 55) >6 months on HAART. After controlling for time-updated laboratory values, the adjusted odds of TB ≤6 months after HAART initiation and >6 months was 0.65 (95% CI: 0.28 to 1.51) and 0.29 (95% CI: 0.16 to 0.53), respectively. TB risk in the first 6 months after HAART initiation is not higher than that before HAART initiation after adjusting for CD4 count and VLs. These findings suggest that short-term TB risk may be related to low CD4 counts and high VLs near HAART initiation and support early HAART initiation to decrease TB risk.

Early HAART Initiation May Not Reduce Actual Reproduction Number and Prevalence of MSM Infection: Perspectives from Coupled within- and between-Host Modelling Studies of Chinese MSM Populations.

Having a thorough understanding of the infectivity of HIV, time of initiating treatment and emergence of drug resistant virus variants is crucial in mitigating HIV infection. There are many challenges to evaluating the long-term effect of the Highly Active Antiretroviral Therapy (HAART) on disease transmission at the population level. We proposed an individual based model by coupling within-host dynamics and between-host dynamics and conduct stochastic simulation in the group of men who have sex with men (MSM). The mean actual reproduction number is estimated to be 3.6320 (95% confidence interval: [3.46, 3.80]) for MSM group without treatment. Stochastic simulations show that given relatively high (low) level of drug efficacy after emergence of drug resistant variants, early initiation of treatment leads to a less (greater) actual reproduction number, lower (higher) prevalence and less (more) incidences, compared to late initiation of treatment. This implies early initiation of HAART may not always lower the actual reproduction number and prevalence of infection, depending on the level of treatment efficacy after emergence of drug resistant virus variants, frequency of high-risk behaviors and etc. This finding strongly suggests early initiation of HAART should be implemented with great care especially in the settings where the effective drugs are limited. Coupling within-host dynamics with between-host dynamics can provide critical information about impact of HAART on disease transmission and thus help to assist treatment strategy design and HIV/AIDS prevention and control.

Impact of highly active antiretroviral therapy on nutritional and immunologic status in HIV-infected children in the low-income country of Ethiopia

ObjectiveHIV/AIDS and malnutrition combine to undermine the immunity of individuals and are inextricably interrelated. Although the effect of highly active antiretroviral therapy (HAART) on growth in HIV-infected children is well known, the influence of prior nutritional and immunologic status on the response to HAART is not well documented. The aim of the present study was to determine the effects of HAART on nutritional and immunological status in HIV-infected children in the low-income country of Ethiopia. MethodsA multicenter, retrospective cohort study was conducted on HIV-infected children receiving antiretroviral therapy at the pediatric units of public hospitals in Addis Ababa (Black Lion, Zewditu, Yekatit 12 and ALERT hospitals), Ethiopia. Nutritional status was defined as stunting (height-for-age Z score [HAZ] <–2), wasting (weight-for-height Z score [WHZ] <–2), and underweight (weight-for-age Z score [WAZ] <–2). Multivariable logistic regression was used to analyze factors associated with treatment success and to establish whether growth (baseline nutritional status) in children predicts immunologic outcomes. In all, 556 HIV-infected children receiving HAART from January 2008 to December 2009 were included in this study. ResultsOver the 24-mo follow-up period, the study showed that the immunologic recovery of stunted and underweight children, regardless of their baseline nutritional status, responded equally to treatment. However, wasted children showed less immunologic recovery at the different follow-up visits. Predictors of positive shift in WHZ after 24 mo of follow-up were advanced disease stage (World Health Organization clinical stages 3 and 4) with odds ratio (OR), 0.25 (95% confidence interval [CI], 0.34–0.99; P = 0.045) and baseline severe underweight OR, 0.19 (95% CI, 0.09–0.56; P = 0.003). The independent predictors of positive shift of growth shift in WAZ over 24 mo were lower baseline age (<36 mo) with OR, 0.21 (95% CI, 0.04–0.90; P = 0.036) and baseline moderate underweight itself with OR, 0.11 (95% CI, 0.05–0.25; P = 0.0001) were predictors of positive shift (shift to normal). ConclusionDespite the apparent growth response in HIV-infected children after initiation of HAART, moderate and severe underweight are both independent predictors of a positive shift. The latter suggests that children on HAART require nutritional supplementation, especially during the early initiation of HAART.

The Role of the Tumor Microenvironment in HIV-Associated Lymphomas

There has been considerable interest in the role of the lymphoma microenvironment. Despite the use of highly active antiretroviral therapy (HAART), AIDS-related diffuse large-B-cell lymphoma remains common and HIV-relatedHIV-associated classical Hodgkin's lymphoma is increasing in incidence. Less is known about the impact HIV and HAART have on the lymphoma microenvironment. AIDS-related diffuse large B-cell lymphoma is highly angiogenic, demonstrates increased lymphoblastic histology, proliferation, increased activated cytotoxic T cells, reduced CD4(+) and FOXP3(+) T cells, but no differences in tumor-associated macrophages. Early initiation of HAART improves immunosurveillance, but cases without viral antigens appear able to avoid immunologic reaction. Increased T cell infiltrates seen with HAART treatment in HIV-related classical Hodgkin's lymphoma may contribute to malignant cell growth.

HIV Drug Therapy in the Americas 16-18 April 2015, Mexico City, Mexico.

HIV Drug Therapy in the Americas 16-18 April 2015, Mexico City, Mexico.

Factors associated with lack of viral suppression at delivery among highly active antiretroviral therapy-naive women with HIV: a cohort study.

A high delivery maternal plasma HIV-1 RNA level (viral load [VL]) is a risk factor for mother-to-child transmission and poor maternal health. To identify factors associated with detectable VL at delivery despite initiation of highly active antiretroviral therapy (HAART) during pregnancy. Multicenter observational study. (ClinicalTrial.gov: NCT00028145). 67 U.S. AIDS clinical research sites. Pregnant women with HIV who initiated HAART during pregnancy. Descriptive summaries and associations among sociodemographic, HIV disease, and treatment characteristics; pregnancy-related risk factors; and detectable VL (>400 copies/mL) at delivery. Between 2002 and 2011, 671 women met inclusion criteria and 13.1% had detectable VL at delivery. Factors associated with detectable VL included multiparity (16.4% vs. 8.0% nulliparity; P=0.002), black ethnicity (17.6% vs. 6.6% Hispanic and 6.6% white; P<0.001), 11th grade education or less (17.6% vs. 12.1% had a high school diploma; P=0.013), initiation of HAART in the third trimester (23.9% vs. 12.3% and 8.6% in the second and trimesters, respectively; P=0.003), having an HIV diagnosis before the current pregnancy (16.1% vs. 11.0% during the current pregnancy; P=0.051), and having the first prenatal visit in the third trimester (33.3% vs. 14.3% and 10.5% in the second and third trimesters, respectively; P=0.002). Women who had treatment interruptions or reported poor medication adherence were more likely to have detectable VL at delivery. Data on many covariates were incomplete because women entered the study at varying times during pregnancy. A total of 13.1% of women who initiated HAART during pregnancy had detectable VL at delivery. The timing of HAART initiation and prenatal care, along with medication adherence during pregnancy, were associated with detectable VL at delivery. Social factors, including ethnicity and education, may help identify women who could benefit from focused efforts to promote early HAART initiation and adherence. U.S. Department of Health and Human Services.

Predictors of early mortality in a cohort of HIV-infected children receiving high active antiretroviral treatment in public hospitals in Ethiopia

Highly active antiretroviral therapy (HAART) is the breakthrough in care and treatment of people living with HIV, leading to a reduction in mortality and an improvement in the quality of life. Without antiretroviral treatment, most HIV-infected children die before their fifth birthday. So the objective of this study is to determine the mortality and associated factors in a cohort of HIV-infected children receiving ART in Ethiopia. A multicentre facility-based retrospective cohort study was done in selected pediatric ART units in hospitals found in Addis Ababa, Ethiopia. The probability of survival was estimated using the Kaplan–Meier method, and multivariate analysis by Cox proportional hazards regression models was conducted to determine the independent predictor of survival. A total of 556 children were included in this study. Of the total children, 10.4% were died in the overall cohort. More deaths (70%) occurred in the first 6 months of ART initiation, and the remaining others were still on follow-up at different hospitals. Underweight (moderate and severe; HR: 10.10; 95% CI: 2.08, 28.00; P = 0.004; and HR: 46.69; 95% CI: 9.26, 200.45; P < 0.01, respectively), advanced disease stage (WHO clinical stages III and IV; HR: 10.13: 95% CI: 2.25, 45.58; P = 0.003), poor ART adherence (HR: 11.72; 95% CI: 1.60, 48.44; P = 0.015), and hemoglobin level less than 7 g/dl (HR: 4.08: 95% CI: 1.33, 12.56; P = 0.014) were confirmed as significant independent predictors of death after controlling for other factors. Underweight, advanced disease stage, poor adherence to ART, and anemia appear to be independent predictor of survival in HIV-infected children receiving HAART at the pediatric units of public hospitals in Ethiopia. Nutritional supplementations, early initiation of HAART, close supervision, and monitoring of patients during the first 6 months, the follow up period is recommended.

CD4 Counts and Mortality in Virologically Suppressed US Veterans

We used the Veterans Health Administration (VA) HIV Clinical Case Registry (CCR) to evaluate the association between annual CD4 averages and all-cause mortality in HIV-infected veterans during their initial episode of suppressive highly active antiretroviral therapy (HAART). We observed 1083 deaths in 14 769 patients. Unadjusted mortality rates in the top and bottom CD4 quintiles differed significantly from the mid CD4 strata. Mortality in the top CD4 quintile (≥720 cells/mm(3)) was 14.1/1000 patient-years, 95% confidence interval (CI): 10.1-18.2, compared with 20.4 (CI: 15.5-25.3) in the next lower CD4 stratum (530-719 cells/mm(3)). This difference was significant in Cox proportional hazards model, controlling for demographics, hepatitis co-infections, low-level viremia, HAART adherence, and refill rates of individual antiretrovirals (HR: 1.4, CI: 1.13-1.73). Our results support early HAART initiation as advocated by the current US treatment guidelines for HIV infection.

The microenvironment of AIDS-related diffuse large B-cell lymphoma provides insight into the pathophysiology and indicates possible therapeutic strategies

AbstractDespite the use of highly active antiretroviral therapy (HAART), AIDS-related lymphoma remains common. We investigated the tumor, microenvironment, and viral components in 41 AIDS-related diffuse large B-cell lymphomas (AR-DLBCLs) in the pre- and post-HAART era. The outcome has improved and the frequency of the prognostically unfavorable immunoblastic histology has decreased after HAART. Compared with sporadic cases, AR-DLBCL demonstrated increased hyperproliferation (P < .001) and c-Myc rearrangements, reduced CD4+ (P < .001) and FOXP3+ T cells (P < .001), increased activated cytotoxic cells (P < .001), but no difference in tumor-associated macrophages. Our analysis showed that AR-DLBCL is highly angiogenic with higher blood-vessel density than sporadic cases (P < .001) and highlighted the role of Epstein-Barr virus in angiogenesis. We recognized viral profiles and as a second step examined the reactive cytotoxic cell infiltrates. Our observation of markedly higher numbers of cytotoxic cells in AR-DLBCL with LMP1 and/or p24 compared with cases lacking viral antigens (P < .001) has important clinical implications, implicitly linked to the immunosurveillance theory. Whereas early initiation of HAART should improve immunosurveillance and reduce the incidence of LMP1-positive AR-DLBCL, cases without viral antigens appear able to avoid immunologic reaction and likely require additional strategies to improve surveillance.

早期の多剤併用療法導入が有効であったHIV関連慢性炎症性脱髄性多発根神経炎の1例

A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment

BackgroundFor antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events.MethodsIn a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART.FindingsA total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar.InterpretationEarly initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability.Trial registrationCTRI/2011/12/002260