Changes in renal function with long-term exposure to antiretroviral therapy in HIV-infected adults in Asia.

PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD). RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

Factors associated with pre-treatment HIV RNA: application for the use of abacavir and rilpivirine as the first-line regimen for HIV-infected patients in resource-limited settings.

BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome. METHODS: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created. RESULTS: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm3; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m2 (OR 2.4 vs. <18.5 kg/m2; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p < 0.01), CD4 count >350 cells/mm3 (OR 3.9 vs. <100 cells/mm3; 95% CI 2.0-4.1, p < 0.01), total lymphocyte count >2000 cells/mm3 (OR 1.7 vs. <1000 cells/mm3; 95% CI 1.3-2.3, p < 0.01), and no prior AIDS-defining illness (OR 1.8; 95% CI 1.5-2.3, p < 0.01). Receiver-operator characteristic (ROC) analysis yielded area under the curve of 0.70 (95% CI 0.67-0.72) among derivation patients and 0.69 (95% CI 0.65-0.74) among validation patients. A cut off score >25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients. CONCLUSION: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.

Impact of peer support on virologic failure in HIV-infected patients on antiretroviral therapy - a cluster randomized controlled trial in Vietnam.

BACKGROUND: The effect of peer support on virologic and immunologic treatment outcomes among HIVinfected patients receiving antiretroviral therapy (ART) was assessed in a cluster randomized controlled trial in Vietnam. METHODS: Seventy-one clusters (communes) were randomized in intervention or control, and a total of 640 patients initiating ART were enrolled. The intervention group received peer support with weekly home-visits. Both groups received first-line ART regimens according to the National Treatment Guidelines. Viral load (VL) (ExaVir™ Load) and CD4 counts were analyzed every 6 months. The primary endpoint was virologic failure (VL >1000 copies/ml). Patients were followed up for 24 months. Intention-to-treat analysis was used. Cluster longitudinal and survival analyses were used to study time to virologic failure and CD4 trends. RESULTS: Of 640 patients, 71% were males, mean age 32 years, 83% started with stavudine/lamivudine/nevirapine regimen. After a mean of 20.8 months, 78% completed the study, and the median CD4 increase was 286 cells/µl. Cumulative virologic failure risk was 7.2%. There was no significant difference between intervention and control groups in risk for and time to virologic failure and in CD4 trends. Risk factors for virologic failure were ART-non-naïve status [aHR 6.9;(95% CI 3.2-14.6); p < 0.01]; baseline VL ≥100,000 copies/ml [aHR 2.3;(95% CI 1.2-4.3); p < 0.05] and incomplete adherence (self-reported missing more than one dose during 24 months) [aHR 3.1;(95% CI 1.1-8.9); p < 0.05]. Risk factors associated with slower increase of CD4 counts were: baseline VL ≥100,000 copies/ml [adj.sq.Coeff (95% CI): -0.9 (-1.5;-0.3); p < 0.01] and baseline CD4 count <100 cells/µl [adj.sq.Coeff (95% CI): -5.7 (-6.3;-5.4); p < 0.01]. Having an HIV-infected family member was also significantly associated with gain in CD4 counts [adj.sq.Coeff (95% CI): 1.3 (0.8;1.9); p < 0.01]. CONCLUSION: There was a low virologic failure risk during the first 2 years of ART follow-up in a rural low-income setting in Vietnam. Peer support did not show any impact on virologic and immunologic outcomes after 2 years of follow up. TRIAL REGISTRATION: NCT01433601 .

HIV sero-discordance among married HIV patients initiating anti-retroviral therapy in northern Vietnam.

BACKGROUND: In many countries in Asia, the HIV epidemic is in a concentrated phase, with high prevalence in certain risk groups, such as men who inject drugs. There is also a rapid increase of HIV among women. The latter might be due to high levels of sero-discordant couples and increasing transmission from male to female partners over time. METHODS: All adult married patients initiating antiretroviral treatment at four out-patient clinics in Quang Ninh province in north-eastern Vietnam between 2007 and 2009 were asked to participate in the study. Clinical information was extracted from patients' records, and a structured questionnaire was used to collect social, demographic and economic data. RESULTS: Two hundred eighty-eight married patients for whom information on the HIV status of their spouse was available were included in the study. Overall, the sero-discordance rate was 58%. The sero-discordance rate was significantly higher among married males, 71% had spouses not infected, than married females, of whom 18% had spouses not infected. Other factors associated with a high rate of sero-discordance were injection drug use (IDU) history, tuberculosis (TB) history and the availability of voluntary counselling and testing (VCT) in residential locations. High sero-concordance was associated with college/university education. CONCLUSION: The sero-discordance was significantly higher among married males than married females. Other factors also related to high sero-discordance were history of IDU, history of TB and the availability of VCT in residential locations. In contrast, college/university education and female sex were significantly related to low sero-discordance. To contain the increasing HIV prevalence among women, measures should be taken to prevent transmission among sero-discordant couples. Trial registration NCT01433601.

Severe malaria not responsive to artemisinin derivatives in man returning from Angola to Vietnam.

Resistance to artemisinin derivatives, the most potent antimalarial drugs currently used, has emerged in Southeast Asia and threatens to spread to Africa. We report a case of malaria in a man who returned to Vietnam after 3 years in Angola that did not respond to intravenous artesunate and clindamycin or an oral artemisinin-based combination.

A Case of Histoplasmosis Detected Through Bone Marrow Analysis.

Histoplasmosis is an endemic infection caused by Histoplasma capsulatum, leading to a broad spectrum of disease from asymptomatic to severe disseminated disease. To diagnose Histoplasmosis, culture remains the gold standard for the laboratory diagnosis; however, this fungus grows slowly, taking a long time 2 to 3 weeks or may take up to 8 weeks. Therefore, some other methods such as bone marrow examination play an essential role in rapid identification and early diagnosis, especially in cases of severe disseminated disease. In this case, we report a 55-year-old man with a 1-year history of gout, self-medicating (including Medrol) who was admitted to the hospital because of persistent fever and swelling of his left arm. About laboratory investigation, there was a bicytopenia (RBC and PLT), blood and pus cultures many times were negative. On the slide of the bone marrow specimen, images of yeast suspected of Histoplasma capsulatum were observed. Therefore, the patient was treated with antifungal medication, and the culture was repeated with prolonged follow-up time and positive results with H. capsulatum after 16 days. In conclusion, bone marrow test plays a significant role in the diagnosis of some fungal infections, which can contribute to an early diagnosis, especially in cases of culture and serological tests are not available or cannot be performed. Patients who present with fever and bicytopenia or pancytopenia should be performed early bone marrow test, which can support the earlier diagnosis to have appropriate treatment.

Effect of Training on Physicians' Palliative Care-Related Knowledge and Attitudes in Vietnam.

CONTEXT: Palliative care remains largely inaccessible in low- and middle-income countries (LMICs), and efforts to increase access are impeded by lack of training of proven effectiveness for physicians. OBJECTIVES: To measure the effectiveness of palliative care training for Vietnamese physicians. METHODS: The palliative care-related knowledge, attitudes, and self-assessment of Vietnamese physicians were studied prior to a basic course in palliative care (baseline), just after the physicians completed the course (post), and 6-18 months later (follow-up). RESULTS: The self-assessment scores and knowledge scores increased significantly from baseline to post and decreased significantly from post to follow-up, but the follow-up scores remained significantly higher than baseline. There were significant interactions between changes over time of the knowledge scores and baseline age, degree, years of graduation, training, type of work, and whether participants had ever prescribed morphine for pain. Medically appropriate attitudes increased significantly from baseline to post and did not decrease significantly from post to follow-up. CONCLUSION: Our basic palliative care course in Vietnam resulted in significant and enduring improvements among physicians in palliative care-related knowledge, attitudes, and self-assessed competence. To respond to the enormous unmet need for palliative care in LMICs, primary care providers and physician-specialists in many fields, among others, should receive palliative care training of proven effectiveness, receive ongoing mentoring or refresher training, and be given the responsibility and opportunity to practice what they learn.

Survival and causes of death among HIV-infected patients starting antiretroviral therapy in north-eastern Vietnam.

BACKGROUND: There is a lack of knowledge on mortality and causes of death among human immunodeficiency virus (HIV)-infected patients after initiation of antiretroviral therapy (ART) in Vietnam. We investigated the mortality rate, risk factors, causes of death, and impact of enhanced adherence support on survival among 640 Vietnamese treatment-naïve HIV-infected patients receiving ART in a cluster randomized controlled trial. METHODS: Patients in the intervention group received enhanced adherence from peer-supporters. Data were collected through medical records and a verbal autopsy questionnaire. We used Kaplan-Meier analysis to describe the survival trends and the Cox proportional hazard model to identify predictors of acquired immune deficiency syndrome (AIDS)-related deaths. RESULTS: After a median follow-up of 15.2 months, there were 60 deaths, 73% of which occurred within 6 months. The mortality rate was 7.4/100 person-y and survival probability was 91% after 1 y. There was no significant difference in mortality rate between the intervention and the control groups. At baseline, the predictive factors for AIDS-related death were age >35 y, clinical stage 3 or 4, body mass index (BMI) <18 kg/m(2), CD4 count <100/µl, haemoglobin level <100 g/l, and plasma viral load >100,000 copies/ml. Tuberculosis (TB) was the most common cause of death (40%). CONCLUSIONS: Early deaths occurred after ART, and delay of ART caused a significant decrease in CD4 count and a high mortality. Adherence support had no impact on survival at the early stage of ART. Early ART initiation and intensive follow-up of patients during the first 6 months of ART are therefore necessary to reduce AIDS-related mortality.

Imaging of cryptococcus neoformans infection in breasts: A case report.

There have been few reports on the imaging characteristics of cryptococcus neoformans (C. neoformans) infection of the breast. Herein, we reported the imaging features of C. neoformans infection of the breast in a 41-year-old woman with immune thrombocytopenic purpura. Bilateral, diffuse, hyperechoic, and well-defined margin lesions were observed on breast ultrasounds. In addition, a global asymmetry in the left breast, and a focal asymmetry in the right breast were observed on mammograms. Breast fine needle aspiration and biopsy results revealed a C. neoformans infection. After 5 months of treatment with oral fluconazole and amphotericin B, the lesion on the right breast disappeared on repeated-breast ultrasounds.

Meningitis patients with Angiostrongylus cantonensis may present without eosinophilia in the cerebrospinal fluid in northern Vietnam.

BACKGROUND: Eosinophilic meningitis (EM) is a rare clinical syndrome caused by both infectious and noninfectious diseases. In tropical pacific countries, Angiostrongylus cantonensis is the most common cause. However, the EM definition varies in the literature, and its relation to parasitic meningitis (PM) remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Adult and adolescent patients of 13 years old or above with suspected central nervous system (CNS) infections with abnormal CSF findings were prospectively enrolled at a tertiary referral hospital in Hanoi, Vietnam from June 2012 to May 2014. Patients with EM or suspected PM (EM/PM) were defined by the presence of either ≥10% eosinophils or an absolute eosinophil cell counts of ≥10/mm3 in the CSF or blood eosinophilia (>16% of WBCs) without CSF eosinophils. In total 679 patients were enrolled: 7 (1.03%) had ≥10% CSF eosinophilia, 20 (2.95%) had ≥10/mm3 CSF eosinophilia, and 7 (1.03%) had >16% blood eosinophilia. The patients with ≥10% CSF eosinophilia were significantly younger (p = 0.017), had a lower body temperature (p = 0.036) than patients with ≥10/mm3 CSF eosinophilia among whom bacterial pathogens were detected in 72.2% (13/18) of those who were tested by culture and/or PCR. In contrast, the characteristics of the patients with >16% blood eosinophilia resembled those of patients with ≥10% CSF eosinophilia. We further conducted serological tests and real-time PCR to identify A. cantonensis. Serology or real-time PCR was positive in 3 (42.8%) patients with ≥10% CSF eosinophilia and 6 (85.7%) patients with >16% blood eosinophilia without CSF eosinophils but none of patients with ≥10/mm3 CSF eosinophilia. CONCLUSIONS: The etiology of PM in northern Vietnam is A. cantonensis. The eosinophil percentage is a more reliable predictor of parasitic EM than absolute eosinophil count in the CSF. Patients with PM may present with a high percentage of eosinophils in the peripheral blood but not in the CSF.

An expanded HIV care cascade: ART uptake, viral load suppression and comorbidity monitoring among adults living with HIV in Asia.

BACKGROUND: Comprehensive treatment and clinical management are central to improving outcomes for people living with HIV (PLHIV). We explored trends in HIV clinical care, treatment outcomes, and chronic kidney disease (CKD) and diabetes monitoring. METHODS: We included patients ≥18 years in care at ten clinical sites in eight Asian countries. Proportions of patients on antiretroviral therapy (ART), with annual viral load, and with viral load suppression (VLS; <1,000 copies/ml) were estimated by year for 2011-2016, stratified by country income level (lower-middle income [LMIC] and high-income countries [HIC]). Among those on ART in 2016 we evaluated factors associated with annual CKD and diabetes monitoring. RESULTS: Among 31,346 patients (67% male), the proportions of patients on ART (median ART initiation year 2011, IQR 2007-2013), with annual viral load and VLS had substantially increased by 2016 (to 94%, 42% and 92%, respectively, in LMIC and 95%, 97% and 93%, respectively, in HIC) with the larger increases over time seen in LMIC. Among those on ART in 2016, monitoring proportions in LMIC were 53% for CKD and 26% for diabetes compared with 83% and 59%, respectively, in HIC. Overall, a decreased odds of monitoring was observed for male gender, heterosexual HIV exposure, no viral load and LMIC. Diabetes monitoring was also decreased in those with viral failure. CONCLUSIONS: Our findings highlight suboptimal monitoring of viral load, CKD and diabetes in PLHIV in Asia. There is a need for affordable and scalable monitoring options to improve the joint care for HIV and non-communicable diseases.

Analysis of the 56-kDa type specific antigen gene of Orientia tsutsugamushi from northern Vietnam.

Scrub typhus has been documented since 1932 in Vietnam, however, the disease burden of scrub typhus remains poorly understood in the country. We conducted this study to describe the phylogenetic analysis of the 56-kDa type-specific antigen (TSA) gene of Orientia tsutsugamushi associated with PCR positive cases of scrub typhus. Of 116 positive samples, 65 type-specific antigen gene sequences were obtained and classified into 3 genogroups: Karp, Kato and Gilliam. The Karp genogroup was the most frequently detected phylogenetic cluster in the study with 30 samples (46%), followed by Kato and Gilliam with 20 (31%) and 15 (23%), respectively. All sequences showed 94-100% nucleotide similarity to reference sequences collected in the central part of Vietnam in 2017. Patients infected with Karp genogroup were more likely to have significant thrombocytopenia than the other genogroups. These results suggest that any scrub typhus vaccine considered for use in Vietnam should provide protection against each of these 3 genogroups.

Palliative Care-Related Knowledge, Attitudes, and Self-Assessment Among Physicians in Vietnam.

CONTEXT: Palliative care is rarely accessible in low- and middle-income countries, and lack of adequate training for health care providers is a key reason. In Vietnam, the Ministry of Health, major hospitals and medical universities, and foreign physician-educators have partnered to initiate palliative care training for physicians. OBJECTIVES: To measure the baseline palliative care-related knowledge, attitudes, and self-assessment of Vietnamese physicians as a basis for curriculum development and to enable evaluation of training courses. METHODS: Before palliative care training courses in Vietnam from 2007 to 2014, we collected data on the participating physicians' demographics, self-assessed competence in palliative care, and palliative care-related knowledge and attitudes. Scores were calculated in three outcome categories-knowledge, attitudes, and self-assessment-and in two subcategories related to physical and psychological symptoms. Associations between the demographic, education, and practice factors and these scores were assessed using linear regression. RESULTS: Among the 392 physicians surveyed, concern about untreated suffering was highly prevalent. 85% felt that most patients with cancer in Vietnam die in pain. On self-assessment, only 8% felt adequately trained in palliative care and the mean knowledge assessment score was 44%. Although 77% had prescribed an opioid in the past year and most had appropriate attitudes toward the use of morphine for pain, the majority reported explicit or implicit restrictions on prescribing morphine. CONCLUSION: There is a great need among Vietnam's physicians for training in palliative care and especially in nonpain and psychological symptom control. Rational, balanced, and clear opioid-prescribing policies are needed to enable physicians to treat pain without fear of repercussions.

Challenges in diagnosing scrub typhus among hospitalized patients with undifferentiated fever at a national tertiary hospital in northern Vietnam.

BACKGROUND: Scrub typhus (ST) is a leading cause of non-malarial febrile illness in Southeast Asia, but evidence of its true disease burden is limited because of difficulties of making the clinical diagnosis and lack of adequate diagnostic tests. To describe the epidemiology and clinical characteristics of ST, we conducted an observational study using multiple diagnostic assays at a national tertiary hospital in Hanoi, Vietnam. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 1,127 patients hospitalized with documented fever between June 2012 and May 2013. Overall, 33 (2.9%) patients were diagnosed with ST by PCR and/or screening of ELISA for immunoglobulin M (IgM) with confirmatory tests: 14 (42.4%) were confirmed by indirect immunoperoxidase assay (IIP), and 19 (57.6%) were by IIP and PCR. Living by farming, conjunctival injection, eschar, aspartate aminotransferase elevation, and alanine aminotransferase elevation were significantly associated with ST cases (adjusted odds ratios (aORs): 2.8, 3.07, 48.8, 3.51, and 4.13, respectively), and having a comorbidity and neutrophilia were significantly less common in ST cases (aORs: 0.29 and 0.27, respectively). The majority of the ST cases were not clinically diagnosed with rickettsiosis (72.7%). Dominant IIP reactions against a single antigen were identified in 15 ST cases, whereas indistinguishably high reactions against multiple antigens were seen in 11 ST cases. The most frequently observed dominant IIP reaction was against Karp antigen (eight cases) followed by Gilliam (four cases). The highest diagnostic accuracy of IgM ELISA in acute samples was 78%. In a phylogenetic analysis of the 56-kDa type-specific antigen gene, the majority (14 cases) were located in the Karp-related branch followed by the Gilliam-related (two cases), Kato-related (two cases), and TA763-related clades (one case). CONCLUSIONS/SIGNIFICANCE: Both the clinical and laboratory diagnoses of ST remain challenging at a tertiary hospital. Implementation of both serological and nucleic acid amplification assays covering endemic O. tsutsugamushi strains is essential.

Effect of Macrolide Prophylactic Therapy on AIDS-Defining Conditions and HIV-Associated Mortality.

BACKGROUND: Mycobacterium avium complex prophylaxis is recommended for patients with advanced HIV infection. With the decrease in incidence of disseminated Mycobacterium avium complex infection and the availability of antiretroviral therapy (ART), the benefits of macrolide prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART. METHODS: Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count <50 cells/mm at ART initiation were included. The effect of macrolide prophylaxis on HIV-associated mortality or AIDS-defining conditions (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted in patients with a CD4 <100 cells/mm at ART initiation. RESULTS: Of 1345 eligible patients, 10.6% received macrolide prophylaxis. The rate of the combined outcome was 7.35 [95% confidence interval (CI): 6.04 to 8.95] per 100 patient-years, whereas the rate of HIV-associated mortality was 3.14 (95% CI: 2.35 to 4.19) per 100 patient-years. Macrolide use was associated with a significantly decreased risk of HIV-associated mortality (hazard ratio 0.10, 95% CI: 0.01 to 0.80, P = 0.031) but not with the combined outcome (hazard ratio 0.86, 95% CI: 0.32 to 2.229, P = 0.764). Sensitivity analyses showed consistent results among patients with a CD4 <100 cells/mm at ART initiation. CONCLUSIONS: Macrolide prophylaxis is associated with improved survival among Asian HIV-infected patients with low CD4 cell counts and on ART. This study suggests the increased usage and coverage of macrolide prophylaxis among people living with HIV in Asia.

Palliative Care in Vietnam: Long-Term Partnerships Yield Increasing Access.

Palliative care began in Vietnam in 2001, but steady growth in palliative care services and education commenced several years later when partnerships for ongoing training and technical assistance by committed experts were created with the Ministry of Health, major public hospitals, and medical universities. An empirical analysis of palliative care need by the Ministry of Health in 2006 was followed by national palliative care clinical guidelines, initiation of clinical training for physicians and nurses, and revision of opioid prescribing regulations. As advanced and specialist training programs in palliative care became available, graduates of these programs began helping to establish palliative care services in their hospitals. However, community-based palliative care is not covered by government health insurance and thus is almost completely unavailable. Work is underway to test the hypothesis that insurance coverage of palliative home care not only can improve patient outcomes but also provide financial risk protection for patients' families and reduce costs for the health care system by decreasing hospital admissions near the end of life. A national palliative care policy and strategic plan are needed to maintain progress toward universally accessible cost-effective palliative care services.

Long-term viral suppression and immune recovery during first-line antiretroviral therapy: a study of an HIV-infected adult cohort in Hanoi, Vietnam.

INTRODUCTION: Achieving viral suppression is key in the global strategy to end the HIV epidemic. However, the levels of viral suppression have yet to be described in many resource-limited settings. METHODS: We investigated the time to virologic failure (VF; defined as a viral load of ≥1000 copies/ml) and changes in CD4 counts since starting antiretroviral therapy (ART) in a cohort of HIV-infected adults in Hanoi, Vietnam. Factors related to the time to VF and impaired early immune recovery (defined as not attaining an increase in 100 cells/mm3 in CD4 counts at 24 months) were further analysed. RESULTS: From 1806 participants, 225 were identified as having VF at a median of 50 months of first-line ART. The viral suppression rate at 12 months was 95.5% and survival without VF was maintained above 90% until 42 months. An increase in CD4 counts from the baseline was greater in groups with lower baseline CD4 counts. A younger age (multivariate hazard ratio (HR) 0.75, vs. <30), hepatitis C (HCV)-antibody positivity (HR 1.43), and stavudine (d4T)-containing regimens (HR 1.4, vs. zidovudine (AZT)) were associated with earlier VF. Factors associated with impaired early immune recovery included the male sex (odds ratio (OR) 1.78), HCV-antibody positivity (OR 1.72), d4T-based regimens (OR 0.51, vs. AZT), and nevirapine-based regimens (OR 0.53, vs. efavirenz) after controlling for baseline CD4 counts. CONCLUSION: Durable high-rate viral suppression was observed in the cohort of patients on first-line ART in Vietnam. Our results highlight the need to increase adherence support among injection drug users and HCV co-infected patients.

Response to hepatitis B vaccination among HIV-infected adults in Vietnam.

OBJECTIVES: We sought to determine the rate of response to hepatitis B (HBV) vaccination among HIV-infected adults in Vietnam. METHODS: We retrospectively abstracted data from a cohort of HIV-infected adults who had received HBV vaccine at an HIV clinic in Hanoi. We examined demographic, clinical and laboratory factors for associations with development of a protective antibody (Ab) response following vaccination (defined as 'responders' with anti-HBs >10 IU/L). RESULTS: Out of 302 HIV-infected patients who completed the vaccine series and follow-up serology testing, 189 (62.6%) had a positive protective Ab response. Female patients had a higher response rate compared to male patients (71.4% vs 56.8%, P=0.01). Among responders, mean CD4 T cell count was 309 cells/µL as compared to 204 cells/µL in non-responders (P<0.0001). On multivariable analysis, CD4 T cell count prior to vaccination was the only factor independently associated with a positive Ab response. Compared to patients with a count less than 100 cells/µL, those with a CD4 T cell count between 100 and 200 cells/µL were 20% more likely to be responders (relative risk [RR] 1.20, 95% confidence interval [CI] 0.77-1.87), those with a CD4 T cell count between 200 and 300 cells/µL were 61% more likely to be responders (RR 1.61, 95% CI 1.05-2.45), and those with a CD4 T cell count greater than 300 cells/µL were 89% more likely to be responders (RR 1.89, 95% CI 1.26-2.83). CONCLUSIONS: We found that the CD4 T cell count at the time of vaccination to be the sole predictor of response to HBV vaccination among HIV-infected Vietnamese adults. Our findings highlight the importance of vaccinating HIV-infected adults prior to advanced immunosuppression.

Elevated CD8 T-cell counts and virological failure in HIV-infected patients after combination antiretroviral therapy.

Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/µL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.