Determinants of virological failure after 1 year's antiretroviral therapy in Vietnamese people with HIV: findings from a retrospective cohort of 13 outpatient clinics in six provinces.

OBJECTIVE: This study examines the proportions and causes of virological failure after one year of antiretroviral therapy (ART) among people living with HIV (PLHIV) in Vietnam. It also evaluates the positive predictive value (PPV) of immunological criteria to detect treatment failure. METHOD: A retrospective cohort of 3449 people with HIV who started ART between 1 January 2005 and 31 December 2009 in 13 outpatient clinics in Vietnam was studied. Multivariate logistic regression modeling was used to calculate crude and adjusted ORs and 95% CIs for associations between patient characteristics and virological failure. RESULTS: An estimated 6.5% (226/3449) of HIV patients in the participating clinics in Vietnam had confirmed virological failure one year after the start of ART. After adjusting for other factors, patients with a baseline CD4 count of 50-100 cells/mm(3) and 101-200 cells/mm(3) were statistically significantly less likely to have virological failure, compared to those with a baseline CD4 count lower than 50 cells/mm(3) (OR=0.61, 95% CI 0.23-0.89; and OR=0.43, 0.18-0.78, respectively). In contrast, patients with a history of injecting drug use were statistically significantly more likely to have viraemia than otherwise (OR=1.32, 1.16-1.67). The PPV of the WHO immunological criteria was 60.1% (57.1-69.3%). CONCLUSIONS: Routine viral load tests should be conducted early to detect virological failure and prevent unnecessary changes to second-line treatments. To improve treatment outcomes, timely ART initiation and adherence to treatment among those with history of injecting drug use should be promoted.

Determinants of antiretroviral therapy initiation and treatment outcomes for people living with HIV in Vietnam.

OBJECTIVES: This study explores patient characteristics that are significantly associated with very late combination antiretroviral therapy (cART) initiation (CD4 count ≤100 cells/mm³) and examines the association between patient characteristics and treatment outcomes, CD4 recovery, and mortality. DESIGN: Data were obtained from the clinical records of 2,198 HIV/AIDS patients in 13 outpatient clinics across 6 provinces in Vietnam. METHODS: Multivariate logistic regression and Cox proportional hazards regression were used to identify patient characteristics that are significantly associated with very late cART initiation and to measure relationships between patient characteristics and treatment outcomes. RESULTS: Very late cART initiation was significantly associated with being male compared with female (odds ratio [OR], 0.36; 95% CI, 0.23-0.58), becoming HIV infected through injecting drugs (OR, 2.13; 95% CI, 1.09-4.14), and having opportunistic infections at cART initiation (OR, 1.69; 95% CI, 1.02-2.86). Being male (female vs male: hazard ratio [HR], 0.45; 95% CI, 0.20-0.98), very late cART initiation (timely vs late: HR, 0.18; 95% CI, 0.04-0.72), low baseline body mass index (BMI) (HR, 0.95; 95% CI, 0.92-0.98), and later baseline WHO clinical stage (WHO clinical stage IV vs combined group of stage I and II: HR, 5.70; 95% CI, 3.90-7.80) were significantly associated with death, whereas being female compared with male (HR, 1.51; 95% CI, 1.14-1.99) and timely cART initiation (HR, 35.45; 95% CI, 13.67-91.91) were significant predictors of CD4 recovery. CONCLUSIONS: Timely testing of patients for HIV, increasing use of CD4 count testing services, and starting cART earlier are essential to reduce mortality and improve treatment outcomes.

Paternal exposure to Agent Orange and spina bifida: a meta-analysis.

The objective of this study is to conduct a meta-analysis of published and unpublished studies that examine the association between Agent Orange (AO) exposure and the risk of spina bifida. Relevant studies were identified through a computerized literature search of Medline and Embase from 1966 to 2008; a review of the reference list of retrieved articles and conference proceedings; and by contacting researchers for unpublished studies. Both fixed-effects and random-effects models were used to pool the results of individual studies. The Cochrane Q test and index of heterogeneity (I(2)) were used to evaluate heterogeneity, and a funnel plot and Egger's test were used to evaluate publication bias. Seven studies, including two Vietnamese and five non-Vietnamese studies, involving 330 cases and 134,884 non-cases were included in the meta-analysis. The overall relative risk (RR) for spina bifida associated with paternal exposure to AO was 2.02 (95% confidence interval [CI]: 1.48-2.74), with no statistical evidence of heterogeneity across studies. Non-Vietnamese studies showed a slightly higher summary RR (RR = 2.22; 95% CI: 1.38-3.56) than Vietnamese studies (RR = 1.92 95% CI: 1.29-2.86). When analyzed separately, the overall association was statistically significant for the three case-control studies (Summary Odds Ratio = 2.25, 95% CI: 1.31-3.86) and the cross sectional study (RR = 1.97, 95% CI: 1.31-2.96), but not for the three cohort studies (RR: 2.11; 95% CI: 0.78-5.73). Paternal exposure to AO appears to be associated with a statistically increased risk of spina bifida.

Cost-effectiveness of antiretroviral therapy expansion strategies in Vietnam.

This study determines an optimal strategy for scaling up ART in Vietnam by examining three initiation thresholds [350 cells/mm(3), 500 cells/mm(3), and treat all people living with HIV (PLHIV) regardless of CD4 cell counts] and treatment commencement rates among treatment-eligible PLHIV ranging from 5% to 100% within 12 months of diagnosis. Incremental cost-effectiveness ratios (ICERs) were calculated using a Markov model, based on data from a cohort of 3449 patients who initiated ART between January 1, 2005 and December 31, 2009 in 13 outpatient clinics across six provinces in Vietnam. Our analyses indicated that raising treatment eligibility criteria, in line with WHO guidelines (CD4 ≤500 cells/mm(3)) or removing CD4-based criteria would both be cost-effective in Vietnam. However, the cost-effective strategy from an economic viewpoint is first to increase coverage substantially among those with lowest CD4 levels, and only when coverage increases towards saturation should initiation criteria be lifted. Universal coverage under current guidelines would cost an additional $85 million and $96 million per year if the treatment threshold was 500 cells/mm(3). These scenarios would avert 15,000 and 22,000 HIV-related deaths in 2010-2019, with ICERs of $500-$660 per QALY gained. It is imperative to increase treatment coverage for newly diagnosed PLHIV in Vietnam according to the current guidelines prior to increasing the CD4 threshold for ART initiation.

Trends in and determinants of loss to follow up and early mortality in a rapid expansion of the antiretroviral treatment program in Vietnam: findings from 13 outpatient clinics.

BACKGROUND: This study aims to describe the trends in and determinants of six month mortality and loss to follow up (LTFU) during 2005-2009 in 13 outpatient clinics in Vietnam. METHOD: Data were obtained from clinical records of 3,449 Vietnamese HIV/AIDS patients aged 18 years or older who initiated ART between 1 January 2005 and 31 December 2009. Mantel-Haenszel chi-square test, log rank test were conducted to examine the trends of baseline characteristics, six month mortality and LTFU. Cox proportional hazards regression models were performed to compute hazard ratio (HR) and 95% Confidence Interval (CI). RESULTS: Though there was a declining trend, the incidence of six month mortality and LTFU remained as high as 6% and 15%, respectively. Characteristics associated with six month mortality were gender (HR females versus males 0.54, 95%CI: 0.34-0.85), years of initiation (HR 2009 versus 2005 0.54, 95%CI: 0.41-0.80), low baseline CD4 (HR 350-500 cells/mm(3) versus <50 cells/mm(3) 0.26, 95%CI: 0.18-0.52), low baseline BMI (one unit increase: HR 0.96, 95%CI: 0.94-0.97), co-infection with TB (HR 1.61, 95%CI: 1.46-1.95), history of injecting drugs (HR 1.58, 95%CI: 1.31-1.78). Characteristics associated with LTFU were younger age (one year younger: HR 0.97, 95%CI: 0.95-0.98), males (HR females versus males 0.82, 95%CI: 0.63-0.95), and poor adherence (HR 0.55, 95%CI: 0.13-0.87). CONCLUSIONS: To reduce early mortality, special attention is required to ensure timely access to ART services, particularly for patients at higher risk. Patients at risk for LTFU after ART initiation should be targeted through enhancing treatment counselling and improving patient tracing system at ART clinics.

Structural barriers to timely initiation of antiretroviral treatment in Vietnam: findings from six outpatient clinics.

In Vietnam, premature mortality due to AIDS-related conditions is commonly associated with late initiation to antiretroviral therapy (ART). This study explores reasons for late ART initiation among people living with HIV (PLHIV) from the perspectives of health care providers and PLHIV. The study was undertaken in six clinics from five provinces in Vietnam. Baseline CD4 counts were collected from patient records and grouped into three categories: very late initiators (≤100 cells/mm(3) CD4), late initiators (100-200 cells/mm(3)) and timely initiators (200-350 cells/mm(3)). Thirty in-depth interviews with patients who started ART and 15 focus group discussions with HIV service providers were conducted and thematic analysis of the content performed. Of 934 patients, 62% started ART very late and 11% initiated timely treatment. The proportion of patients for whom a CD4 count was obtained within six months of their HIV diagnosis ranged from 22% to 72%. The proportion of patients referred to ART clinics by voluntary testing and counselling centres ranged from 1% to 35%. Structural barriers to timely ART initiation were poor linkage between HIV testing and HIV care and treatment services, lack of patient confidentiality and a shortage of HIV/AIDS specialists. If Vietnam's treatment practice is to align with WHO recommendations then the connection between voluntary counselling and testing service and ART clinics must be improved. Expansion and decentralization of HIV/AIDS services to allow implementation at the community level increased task sharing between doctors and nurses to overcome limited human resources, and improved patient confidentiality are likely to increase timely access to HIV treatment services for more patients.