Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.

INTRODUCTION:In resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. METHODS:This retrospective study, conducted in 2010-2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia) assessed virological failure (VF) rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL) was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF) (>1,000 copies/ml) underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. RESULTS:On a total of 209 patients, 164 (78.4%) were naive and 45 (21.5%) were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30-194) and 279 cells/mm3 (IQR: 103-455) (p<0.001), respectively. Twenty seven patients (12.9%) exhibited VF (95% CI: 8.6-18.2%), including 10 naive (10/164, 6.0%) and 17 pre-treated (17/45, 37.8%) patients (p<0.001). Among these viremic patients, twenty-two (81.4%) were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3%) harbored ≥1 drug resistance mutations (DRMs) whereas 3 (all belonging to pre-treated patients) harbored wild-types viruses. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%). Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations. CONCLUSION:In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre-treated patients infection should be considered as well

Short communication: three years follow-up of first-line antiretroviral therapy in cambodia: negative impact of prior antiretroviral treatment.

International audienceAbstract There are few long-term data on ART-experienced patients in resource-limited settings. We performed a cross-sectional study of HIV-infected patients included in the ESTHER program in Calmette hospital, Phnom Penh, Cambodia, after 36 ± 3 months of cART. Therapeutic, clinical, and immunovirological outcomes were compared between patients who stated they were ART-naive (naive group), dual nucleoside reverse-transcriptase inhibitor (two-NRTI group), or fixed-dose combination of stavudine/lamivudine/nevirapine experienced (three-drug group) at entry to the program. A logistic regression model was used to evaluate the factors associated with virological failure (PCR HIV > 250 copies/ml). Among the 256 patients included in the analysis, 148 (58%) were ART naive while 50 (20%) had previously received two NRTIs and 58 (22%) three drugs. At entry to the program, all the patients received two NRTIs and one nonnucleoside reverse-transcriptase inhibitor (NNRTI). At evaluation, 46 patients (18%) were switched to a protease inhibitor-based regimen (9%, 32%, and 29% of the naive, two-NRTI, and three-drug groups; p < 0.0001). The median CD4 cell count increase was 180/μl overall (IQR: 96-276) and was higher in ART-naive than ART-experienced patients. In the intent-to-treat analysis, virological success was achieved in 83.5%, 67%, and 69% of the naive, two-NRTI, and three-drug groups, respectively (p = 0.002). Factors associated with virological failure were suboptimal previous ART exposure and WHO immunological failure criteria. The long-term efficacy of first-line cART is maintained in Cambodia. In ART-experienced patients, viral load monitoring needs to be available to establish early virological failure and preserve the potency of second line regimens

Outcomes and predictors used in the Framingham, D:A:D, and Rama-EGAT scoring systems.

<p>Outcomes and predictors used in the Framingham, D:A:D, and Rama-EGAT scoring systems.</p

Dyslipidemias and Elevated Cardiovascular Risk on Lopinavir-Based Antiretroviral Therapy in Cambodia

<div><p>Background</p><p>Lopinavir/ritonavir (LPV/r) is widely used in Cambodia with high efficacy but scarce data exist on long-term metabolic toxicity.</p><p>Methods</p><p>We carried out a cross-sectional and retrospective study evaluating metabolic disorders and cardiovascular risk in Cambodian patients on LPV/r-based antiretroviral therapy (ART) for > 1 year followed in Calmette Hospital, Phnom Penh. Data collected included cardiovascular risk factors, fasting blood lipids and glucose, and retrospective collection of bioclinical data. We estimated the 10-year risks of coronary heart disease with the Framingham, Ramathibodi-Electricity Generating Authority of Thailand (Rama-EGAT), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) risk equations. We identified patients with LDL above targets defined by the French expert group on HIV and by the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group (IDSA-AACTG).</p><p>Results</p><p>Of 115 patients enrolled—mean age 40.9 years, 69.2% male, mean time on LPV/r 3.8 years—40 (34.8%) had hypercholesterolemia (> 2.40 g/L), and 69 (60.0%) had low HDL cholesterol (< 0.40 g/L). Twelve (10.5%), 28 (24%) and 9 (7.7%) patients had a 10-year risk of coronary heart disease ≥ 10% according to the Framingham, D:A:D, and Rama-EGAT score, respectively. Fifty one (44.4%) and 36 (31.3%) patients had not reached their LDL target according to IDSA-AACTG and French recommendations, respectively.</p><p>Conclusion</p><p>Prevalence of dyslipidemia was high in this cohort of HIV-infected Cambodian patients on LPV/r. Roughly one third had high LDL levels requiring specific intervention.</p></div

Frequency of mutation by molecule in naive and ART pre-treated patients with virological failure.

<p>Frequency of mutation by molecule in naive and ART pre-treated patients with virological failure.</p

Individual characteristics of patients at intermediate or high cardiovascular risk.

<p>Individual characteristics of patients at intermediate or high cardiovascular risk.</p

RTI-RAMs in ART naive and ART pre-treated patients with virological failure.

<p>RTI-RAMs in ART naive and ART pre-treated patients with virological failure.</p

Evolution of lipid levels between ART-initiation of antiretroviral treatment, switch to lopinavir/ritonavir and evaluation (N = 70).

<p>Evolution of lipid levels between ART-initiation of antiretroviral treatment, switch to lopinavir/ritonavir and evaluation (N = 70).</p

General characteristics, dyslipidemias, cardiovascular risk factors, risk of coronary heart disease at 10 years, and Low-Density Lipoprotein cholesterol levels based on cardiovascular risk in Cambodian HIV-infected patients on Lopinavir-based ART for 1 year or more (N = 115).

<p>General characteristics, dyslipidemias, cardiovascular risk factors, risk of coronary heart disease at 10 years, and Low-Density Lipoprotein cholesterol levels based on cardiovascular risk in Cambodian HIV-infected patients on Lopinavir-based ART for 1 year or more (N = 115).</p

Characteristic of new patients enrolled at Calmette Hospital.

<p>Characteristic of new patients enrolled at Calmette Hospital.</p