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

Family Health International, Phnom Penh, Cambodia.
Journal of the International AIDS Society (Impact Factor: 4.21). 03/2011; 14:14. DOI: 10.1186/1758-2652-14-14
Source: PubMed

ABSTRACT 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.
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.
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.
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.

Download full-text


Available from: Janin Nouhin, Jul 07, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: A growing proportion of patients on antiretroviral therapy in resource-limited settings have switched to second-line regimens. We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings. Two reviewers independently searched four databases and three conference websites. Full text articles were screened and data extracted using a standardized data extraction form. We retrieved 5812 citations, of which 19 studies reporting second-line failure rates in 2035 patients across low-income and middle-income countries were eligible for inclusion. The cumulative pooled proportion of adult patients failing virologically was 21.8, 23.1, 26.7 and 38.0% at 6, 12, 24 and 36 months, respectively. Most studies did not report adequate information to allow discrimination between drug resistance and poor adherence as reasons for virological failure, but for those that did poor adherence appeared to be the main driver of virological failure. Mortality on second-line was low across all time points. Rates of virological failure on second-line therapy are high in resource-limited settings and associated with duration of exposure to previous drug regimens and poor adherence. The main concern appears to be poor adherence, rather than drug resistance, from the limited number of studies accessing both factors. Access to treatment options beyond second-line remains limited and, therefore, a cause for a concern for those patients in whom drug resistance is the identified cause of virological failure.
    AIDS (London, England) 02/2012; 26(8):929-38. DOI:10.1097/QAD.0b013e328351f5b2 · 6.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Citation: Nerrienet E, Nouhin J, Ngin S, Segeral O, Ken S, et al. (2012) HIV-1 Protease Inhibitors Resistance Profiles in Patients with Virological Failure on LPV/r-based 2nd Line Regimen in Cambodia. J AIDS Clinic Res S5:003. Abstract Objective: To describe the ARV resistance profiles of patients experiencing virological failure after at least 6 months on LPV /r -based 2 nd line regimen in Cambodia. Design: Retrospective analysis of resistance testing of 89 patients with detectable viral load under LPV /r -based 2 nd line regimen. Methods: Bulk sequencing of HIV-1 protease, reverse transcriptase and integrase PCR products. Results: Protease gene amplification was successful for 71/89 patients (80%). All were infected by CRF01_AE viruses. Among them, 42 did not present any resistance to PIs. A high level of resistance to PIs was observed for the 29 remaining patients. Twenty-six were resistant to LPV /r (8 possibly resistant). Twenty-eight, 21 and 20 were also found resistant to IDV, ATV/ r and FPV/ r , respectively. Twenty-six were resistant to NFV (11 possibly) and 22 to SQV/ r (9 possibly). Finally, 22/29 (75.8%) were resistant to at least 3 PIs. Interestingly, 78.6% (22/29) were found sensitive to DRV/ r . In this group, a high frequency of resistance to RTIs including ETV was also reported. No resistance to raltegravir (RAL) or elvitegravir (EVG) was observed (n=24). Detailed ARV histories documented for 15 patients revealed past exposition to multiple RTIs and PIs. Conclusion: Almost 2/3 of patients (60/89) with virological failure on LPV /r -based 2 nd line in our study were not in urgent need for treatment change. In contrast, switching treatment was clearly required for 1/3 (29/89) presenting high level of resistance to PIs and RTIs. For those patients, DRV, RAL/EVG, and potentially ETV, could be good candidates for 3 rd line ARV regimen if available.
    Journal of AIDS & Clinical Research 06/2012; DOI:10.4172/2155-6113.S5-003 · 6.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVES: We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. METHODS: We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. RESULTS: Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm(3). Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). CONCLUSION: Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings.
    Journal of Antimicrobial Chemotherapy 08/2012; 67(12). DOI:10.1093/jac/dks310 · 5.44 Impact Factor