Projecting the epidemiological effect, cost-effectiveness and transmission of HIV drug resistance in Vietnam associated with viral load monitoring strategies.

OBJECTIVES: The objective of this study was to investigate the potential epidemiological impact of viral load (VL) monitoring and its cost-effectiveness in Vietnam, where transmitted HIV drug resistance (TDR) prevalence has increased from <5% to 5%-15% in the past decade. METHODS: Using a population-based mathematical model driven by data from Vietnam, we simulated scenarios of various combinations of VL testing coverage, VL thresholds for second-line ART initiation and availability of HIV drug-resistance tests. We assessed the cost per disability-adjusted life year (DALY) averted for each scenario. RESULTS: Projecting expected ART scale-up levels, to approximately double the number of people on ART by 2030, will lead to an estimated 18 510 cases (95% CI: 9120-34 600 cases) of TDR and 55 180 cases (95% CI: 40 540-65 900 cases) of acquired drug resistance (ADR) in the absence of VL monitoring. This projection corresponds to a TDR prevalence of 16% (95% CI: 11%-24%) and ADR of 18% (95% CI: 15%-20%). Annual or biennial VL monitoring with 30% coverage is expected to relieve 12%-31% of TDR (2260-5860 cases), 25%-59% of ADR (9620-22 650 cases), 2%-6% of HIV-related deaths (360-880 cases) and 19 270-51 400 DALYs during 2015-30. The 30% coverage of VL monitoring is estimated to cost US$4848-5154 per DALY averted. The projected additional cost for implementing this strategy is US$105-268 million over 2015-30. CONCLUSIONS: Our study suggests that a programmatically achievable 30% coverage of VL monitoring can have considerable benefits for individuals and leads to population health benefits by reducing the overall national burden of HIV drug resistance. It is marginally cost-effective according to common willingness-to-pay thresholds.

Pretreatment HIV-1 drug resistance to first-line drugs: results from a baseline assessment of a large cohort initiating ART in Vietnam, 2009-10.

OBJECTIVES: The objective of this study was to determine the prevalence and correlates of pretreatment drug resistance (PDR) to first-line antiretroviral drugs among people initiating therapy for HIV in Vietnam. METHODS: Blood was collected during November 2009 to October 2010 from people consecutively initiating ART in four purposively selected public outpatient clinics in three Vietnamese cities. At each study site, recruitment lasted for 6-10 months until the target sample size (range 120-130 individuals) had been reached. The viral load was measured in 501 samples; 490 samples (viral load ≥1000 copies/mL) were genotyped using a nucleotide population-based sequencing assay. Self-reported demographic and clinical data were elicited through interviews. We classified drug-resistance-associated mutations (DRMs) according to the 2009 WHO surveillance list. RESULTS: DRMs were identified in 17/490 participants (3.5%; 95% CI 2.2%-5.5%). The prevalence of DRMs was 1.6% (8/490) against NRTIs, 1.6% (8/490) against NNRTIs and 0.8% (4/490) against PIs; three (0.6%) participants were resistant to both NRTIs and NNRTIs. The overall prevalence of PDR to first-line drugs was low [2.7% (13/490); 95% CI 1.6%-4.4%]. The prevalence of PDR to first-line drugs was greater among 198 HIV-infected participants who injected drugs than among 286 participants who reported risks for sexually acquired HIV (4.0% versus 1.4%, P = 0.079). Multivariable logistic regression analysis suggested that PDR to first-line drugs was significantly higher among people who injected drugs (OR = 3.94; 95% CI 1.13-13.68). CONCLUSIONS: With low PDR, first-line ART may be effective in Vietnam and pretreatment genotyping may be unnecessary. Continuing strategies for the prevention and surveillance of antiretroviral resistance are important for maintaining a low prevalence of antiretroviral resistance in Vietnam. The association between resistance and injection drug use warrants further research.

HIV-1 drug resistance and associated factors among adults failing first-line highly active antiretroviral therapy in Ho Chi Minh City, Vietnam.

BACKGROUND & OBJECTIVES: Little is known about HIV-1 drug resistance (HIVDR) in people failing first-line highly active antiretroviral therapy (HAART) in Vietnam. The aim of this study was to investigate the frequency of HIV-1 drug resistance mutations (DRMs) and determine correlates of acquiring genotypic HIVDR among Vietnamese adults (age ≥ 18) who met the immunological or clinical criteria of first-line HAART failure according to the guidelines of the World Health Organization (WHO). METHODS: A total of 138 individuals participated in a descriptive study in Ho Chi Minh City between 2006 and 2009. Blood samples were collected for performing HIV-1 viral load (VL) and genotyping for specimens with VL ≥ 1,000 copies/mL. Stanford algorithm was used to interpret DRMs and multivariate analyses were performed to investigate predictors of HIVDR acquisition. RESULTS: Of the study population, most participants failed either stavudine/lamivudine/nevirapine or stavudine/lamivudine/efavirenz (116 individuals). Up to 51 people obtained a VL <1,000 copies/mL. Among 87 participating individuals with VL ≥1,000 copies/mL, 11 people still harbored a wild-type strain, while 76 participants harbored a HIV-1 drug-resistant strain (2 of which were against protease inhibitors); common DRMs were M184I/V (74%), Y181I/C/V (39%), G190A/S (32%), T215Y/F (32%), and K103N (31%). The proportions of K65R, Q151M, and T69 insertion were 13%, 11%, and 5%, respectively. Being antiretroviral-exposed before initiating first-line HAART in a public and free-of-charge outpatient clinic, having nonadherence to first-line HAART, per 12-month increase of duration on first-line HAART, and having clinical failure criteria were significantly associated with a genotypic HIVDR acquisition. CONCLUSIONS: In the absence of VL for the population with WHO immunological/ clinical treatment failure criteria, a large proportion of people still achieved a VL <1,000 copies/mL, while a high prevalence of HIVDR was observed in those with VL ≥1,000 copies/mL. Thus, VL monitoring should be implemented now for the HAART-treated population in Vietnam.

Correlation between HIV and sexual behavior, drug use, trichomoniasis and candidiasis among female sex workers in a Mekong Delta province of Vietnam.

To determine the prevalence of HIV and correlates of HIV infection among female sex workers (FSWs) in Soc Trang province, Vietnam, a survey of 406 FSWs in Soc Trang province was conducted between May and August, 2003. The participants were interviewed, using a standardized interview, to obtain information about socio-demographic and behavioral characteristics, and gynecologic and sexually transmitted infection (STI) history. The prevalence of HIV was 3.3%. An increased risk for HIV was associated with ever using illicit drugs, direct sex work, early sexual debut, age of FSWs, and infection with candidiasis and trichomoniasis. Reduced likelihood of HIV was only associated with withdrawal as a contraceptive method. A strong association of HIV with drug use and candidiasis and trichomoniasis infection among FSWs was found. Needle/syringe exchange, STI treatment, and methadone programs targeting FSWs should be implemented, and should include 100% condom use promotion.

Distinctive NK-cell receptor repertoires sustain high-level constitutive NK-cell activation in HIV-exposed uninfected individuals.

We have previously associated high natural killer (NK)-cell activity and protection against HIV-1 infection in Vietnamese exposed uninfected intravascular drug users (EUs). Considering that activating and inhibitory signals sensed by NK-cell receptors regulate NK-cell activation, we performed phenotypic and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) transcript analyses of the NK-cell receptor (NKR) repertoire in 25 EUs, 19 HIV(+) intravenous drug users, and 26 uninfected blood donors. Although NK-cell activation was not linked to a unique NKR repertoire in EUs, various patterns consistent with NK-cell activation were detected in EUs: high KIR3DS1/KIR3DL1 ratio associated with down-regulated KIR3DL1 transcript levels, KIR2DL3(+) low-affinity receptor expansion associated to group HLA-C1 ligand in 2DS2(-)/2DL2(-) EUs, enhanced NKG2C/NKG2A ratio, and increased CD69 expression. Remarkably, EUs exhibited high constitutive degranulation activity in the absence of exogenous stimulation, as shown by the CD107a assay. Furthermore, CD161 expression was increased within the CD107a(+) NK-cell compartment. Our results suggest that in response to viral exposition, particular genetic or regulated features of the NKR repertoire of EUs contribute to their high constitutive NK-cell potential. This might allow NK cells to generate a more rapid and effective immune response to HIV-1, thereby contributing to prevention toward infection.