Positive Virological Outcomes of HIV-Infected Patients on Protease Inhibitor-Based Second-Line Regimen in Cambodia: The ANRS 12276 2PICAM Study.

BACKGROUND: Assessment of virological outcomes among HIV-infected patients receiving protease (PR) inhibitor-based second-line regimen are uncommon in Cambodia. The objective of this study is to assess the virological effectiveness of this regimen as well as impact of adherence boosting for patients experiencing virological failure. METHODS: The 2PICAM study (Clinicaltrial: NCT01801618) is a cross-sectional study of HIV-infected adults on PR inhibitor-based second-line regimen since at least 6 months, conducted in 13 representative sites, comprising more than 90% of the target population. Adults with HIV RNA above 250 copies/mL (threshold of the assay) at inclusion received boosted adherence counseling during 3 months followed by HIV RNA control. For confirmed virological failure, genotype resistance test was performed and expert committee used results for therapeutic decision. RESULTS: Among the 1,317 adults enrolled, the median duration of second-line regimen was 5 years. At inclusion, 1,182 (89.7%) patients achieved virological success (<250 copies/mL) and 135 (10.3%) experienced a virological failure (>250 copies/mL). In multivariable analysis, factors associated with virological success were: CD4 cell count between 201 and 350/mm3 (OR: 4.66, 95% CI: 2.57-8.47, p < 0.0001) and >350/mm3 (OR: 6.67, 95% CI: 4.02-11.06, p < 0.0001), duration of PI-based regimen >2 years (OR: 1.64, 95% CI: 1.03-2.62, p = 0.037), ATV-containing regimen (0R: 1.65, 95% CI: 1.04-2.63, p = 0.034) and high level of adherence (OR: 2.41, 95% CI: 1.07-5.41, p = 0.033). After adherence counseling, 63 (46.7%) patients were rescued while 72 (53.3%) were not. For the 54 patients with genotype resistance tests available, high or intermediate levels of resistance to lopinavir, atazanavir, and darunavir were reported for 13 (24%), 12 (22.2%), and 2 (3.7%) patients, respectively. Change to an alternative PR inhibitor-based regimen was recommended for 17 patients and to third-line regimen, including integrase inhibitors for 12. CONCLUSION: This study reports high rate of virological suppression of second-line regimen and importance of adherence boosting prior to deciding any change of ART regimen. Genotype resistance tests appear necessary to guide decisions. Such information was of great importance for National HIV Program to adapt guidelines and program needs for third-line regimen.

Implementation and Operational Research: Scaling Up the Provision of the PMTCT Services, Using the Linked Response Approach in Cambodia From 2008 to 2012.

INTRODUCTION: In Cambodia, the Linked Response (LR) approach for strengthening linkages between HIV and reproductive health services, especially for the prevention of mother-to-child transmission of HIV (PMTCT), was scaled up in 2009. This article describes the LR scale-up and the concomitant evolution of key PMTCT indicators at the national level. METHODS: A descriptive analysis of routine LR, PMTCT programme data, and national laboratory data from 2008 to 2012 was conducted. RESULTS: LR data show that between 2008 and 2012, the number of LR/PMTCT sites increased from 67 to 956 (of 1004) public health facilities to cover 74 (of 77) operational districts. In LR operational districts, the number of pregnant women (PW) tested for HIV increased from 41,800 in 2009 to 269,935 [of whom 375 (0.14%) were newly tested positive for HIV] in 2012; the number of PW living with HIV and exposed infants receiving antiretrovirals increased from 49 and 44 in 2009 to 720 and 551 in 2012, respectively. Concomitantly, national PMTCT programme data showed that the percent of PW tested for HIV increased from 34.4% (117,832 of 342,929 estimated PW) in 2008 to 86.1% (324,996 of 377,340) in 2012. In 2012, 65.3% (862 of 1321) of estimated HIV-positive PW and 72.7% (960 of 1321) of exposed infants received antiretrovirals. By 6-8 weeks postpartum, 7.4% (8 of 108) and 1.5% (6 of 409) of DNA-polymerase chain reaction tested positive in 2008 and in 2012, respectively. CONCLUSIONS: The LR approach provided a model, which catalyzed increased access of PW to HIV testing and treatment, thereby contributing to the scale-up of PMTCT service provision and improved coverage in Cambodia.

High efficacy of lopinavir/r-based second-line antiretroviral treatment after 24 months of follow up at ESTHER/Calmette Hospital in Phnom Penh, Cambodia.

BACKGROUND: The number of patients on second-line highly active antiretroviral therapy (HAART) regimens is increasing in resource-limited settings. We describe the outcomes after 24 months for patients on LPV/r-based second-line regimens followed up by the ESTHER programme in Phnom Penh, Cambodia. METHODS: Seventy patients who initiated second-line HAART regimens more than 24 months earlier were included, and immuno-virological data analyzed. HIV RNA viral load was determined by real-time RT-PCR. HIV-1 drug resistance was interpreted according to the ANRS algorithm. RESULTS: Of the 70 patients, two were lost to follow up, three died and 65 (92.8%) remained on second-line treatment after 24 months of follow up (median duration of treatment: 27.4 months). At switch to second-line, the median CD4 T cell count was 106 cells/mm³ and the median viral load was 4.7 Log10. Second-line regimens prescribed were ddI/3TC/LPV/r (65.7%), ddI/TDF/LPV/r (10.0%), ddI/AZT/LPV/r (8.6%) and TDF/3TC/LPV/r (7.1%). The median CD4 T cell gain was +258 cells/mm³ at 24 months (n = 63). After 24 months of follow up, 92.3% (60/65) of the patients presented undetectable viral loads, giving an overall treatment success rate of 85.7% (CI: 75.6- 92.0) in intent-to-treat analysis. CONCLUSIONS: These data suggest that a LPV/r-based second-line regimen is associated with a high rate of virological suppression and immune reconstitution after 24 months of follow up in Cambodia.