Predictor Factors for Treatment Failure among Patients on Second Line Antiretroviral Therapy

Second line antiretroviral therapy (ART) regimen is
used when patients fail their first line regimen. There are many
factors such as non-adherence, drug resistance as well as virological
and immunological failure that lead to second line highly active
antiretroviral therapy (HAART) regimen treatment failure. This study
was aimed at determining predictor factors to treatment failure with
second line HAART and analyzing median survival time.
An observational, retrospective study was conducted in Sungai
Buloh Hospital (HSB) to assess current status of HIV patients treated
with second line HAART regimen. Convenience sampling was used
and 104 patients were included based on the study’s inclusion and
exclusion criteria. Data was collected for six months i.e. from July
until December 2013. Data was then analysed using SPSS version 18.
Kaplan-Meier and Cox regression analyses were used to measure
median survival times and predictor factors for treatment failure.
The study population consisted mainly of male subjects, aged 30-
45 years, who were heterosexual, and had HIV infection for less than
6 years. The most common second line HAART regimen given was
lopinavir/ritonavir (LPV/r)-based combination. Kaplan-Meier
analysis showed that patients on LPV/r demonstrated longer median
survival times than patients on indinavir/ritonavir (IDV/r) based
combination (p<0.001). The commonest reason for a treatment to fail
with second line HAART was non-adherence. Based on Cox
regression analysis, other predictor factors for treatment failure with
second line HAART regimen were age and mode of HIV
transmission.





References:
[1] Global AIDS response progress report. http://www.unaids.org/en/
dataanalysis/knowyourresponse/countryprogressreports/2012countries/c
e_MY_Narrative_Report.pdf (2012, assessed 29 March 2014).
[2] Malaysia Ministry of Health. Guidelines for the management of adult
HIV infection with antiretroviral therapy. http://www.moh.gov.my/
images/gallery/Garispanduan/HIVGUIDELINES.pdf (2011, assessed 30
December 2013).
[3] Malaysia Ministry of Health. Country Health Plan 2011-2015, 10th
Malaysia Plan. http://www.moh.gov.my/images/gallery/Report/
Country_health.pdf (2012, assessed 29 March 2014).
[4] R. Manfredi, F. Chiodo, "Limits of deep salvage antiretroviral therapy
with nelfinavir plus either efavirenz or nevirapine, in highly pre-treated
patients with HIV disease,” International journal of antimicrobial
agents,vol. 17, issue 6, pp. 431-548, June 2001.
[5] Clinical protocol for the WHO Europian region. Patient evaluation and
antiretroviral treatment for adults and adolescents.
http://www.euro.who.int/__data/assets/pdf_file/0019/78112/E90840_Ch
apter_1.pdf (2012, assessed 29 July 2014).
[6] MSF access campaign Switzerland. Untangling the web of antiretroviral
price reductions. http://www.msfaccess.org/sites/default/files/
MSF_UTW_17th_Edition_4_b.pdf (2014, assessed 20 July 2014).
[7] M. Pujades-Rodríguez, D. O'Brien, P. Humblet, A. Calmy, "Second-line
antiretroviral therapy in resource-limited settings: the experience of
Médecins Sans Frontières,” Aids, vol. 11, issue 22, pp.1305-12. July
2008.
[8] E. Humphreys, L Chang, J Harris, "Antiretroviral regimens for patients
with HIV who fail first-line antiretroviral therapy,” Cochrane Database
of Systematic Review, vol. 16, issue 6, Jun 2010.
[9] R. Gupta, M. Jordan, B. Sultan, A. Hill, D. Davis, J. Gregson et al,
"Global trends in antiretroviral resistance in treatment-naive individuals
with HIV after rollout of antiretroviral treatment in resource-limited
settings: a global collaborative study and meta-regression analysis,”
Lancet,vol. 380, issue 9849, pp. 1250-8, Oct 2012.
[10] World Health Organization. Antiretroviral therapy for HIV infection in
adults and adolescents: recommendations for a public health approach.
http://www.who.int/hiv/pub/arv/adult2010/en/ (2010, assessed 29 March
2014).
[11] J. Molina, J. Andrade-Villanueva,J. Echevarria, P. Chetchotisak, J.
Corral, N. David et al,"Once-daily atazanavir/ritonavir versus twicedaily
lopinavir/ritonavir, each in combination with tenofovir and
emtricitabine, for management of antiretroviral-naive HIV-1-infected
patients: 48 week efficacy and safety results of the CASTLE study,”
Lancet, vol. 372, issue 9639, pp. 646-55, 2008.
[12] R. Ortiz, E. Dejesus, H. Khanlou, E. Voronin, J. van Lunzen, J.
Andrade-Villanueva et al,"Efficacy and safety of once-daily
darunavir/ritonavir versus lopinavir/ritonavir in treatment naive HIV-1-
infected patients at week 48,”AIDS, vol. 22, issue 12, pp. 1389-97, 2008.
[13] K. Smith, W. Weinberg, E. Dejesus, M. Fischl, Q. Liao, L. Ross et al,
"Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg,
plus tenofovir/emtricitabine, for the initial treatment of HIV infection:
48-week results of ALERT,”AIDS Research and Therapy; vol. 5, issue
5, March 2008.
[14] A. Mills,M. Nelson, D. Jayaweera, K. Ruxrungtham, I. Cassetti, P.
Girard et al,"Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in
treatment-naive, HIV-1-infected patients: 96- week analysis,” AIDS,vol.
23, issue 13, pp. 1679-88. 2009.
[15] A. Jarez-Garcia, G. Martinez-Rivera, B. Donato,"Cost-effectiveness of
atazanavir/ritonavir (Atv+Rtv) compared with lopinavir/ritonavir
(Lpv+Rtv) in treatment-naïve Hiv-infected patients in Mexico: a model
based on the Castle Study,”Value in Health, vol. 14, issue 3, pp. A117–
8, 2011.
[16] K. Simpson, R. Baran,B. Dietz, "Economic and health related quality of
life (HRQL) comparison of lopinavir/ritonavir (LPV/R) and atazanavir
plus ritonavir (ATV+RTV)-based regimens for antiretroviral (ARV)
experienced Brazilian patients,”Value in Health, vol. 14, issue 7, pp.
A270, 2011.
[17] M. Bongiovanni, P. Cicconi,S. Landonio, P. Meraviglia,L. Testa, A. Di
Biagio et al, "Predictive factors of lopinavir/ritonavir discontinuation for
drug-related toxicity: results from a cohort of 416 multi-experienced
HIV-infected individuals,”International journal of antimicrobial agents,
vol. 26, issue 1, pp. 88–91, 2005.
[18] W. Manosuthi, S. Sungkanuparph, "Effectiveness and metabolic
complications after 96 weeks of a generic fixed-dose combination of
stavudine, lamivudine , and nevirapine among antiretroviral-naive
advanced HIV-infected patients in Thailand: a prospective study,”
Current Therapeutic Research, Clinical and Experimental, vol. 69, issue
1, pp. 90–100. Feb 2008.
[19] D. Paterson, S. Swindells, J. Mohr,"Adherence to protease inhibitor
therapy and outcomes in patients with HIV infection,”Annalsof Internal
Medicine, vol. 133, pp. 21-30, 2000.
[20] M. Bongiovanni, T. Bini,E. Chiesa,P. Cicconi, P,F. Adorni, A.
d’Arminio, "Lopinavir/ritonavir vs. indinavir/ritonavir in antiretroviral
naive HIV-infected patients: immunovirological outcome and side
effects,”Antiviral research, vol. 62, issue 1, pp. 53–6. 2004
[21] P. Barreiro,N. Camino,C. de Mendoza, L. Valer,M. Núñez,
"Comparison of the efficacy, safety and predictive value of HIV
genotyping using distinct ritonavir-boosted protease inhibitors,”
International journal of antimicrobial agents, vol. 20, issue 6, pp. 438–
43, 2002.
[22] A. Phillips,C. Leen, A. Wilson,J. Anderson, D. Dunn, "Risk of extensive
virological failure to the three original antiretroviral drug classes over
long-term follow-up from the start of therapy in patients with HIV
infection: an observational cohort study,”Lancet, vol. 370, issue 9603,
pp. 1923–8. 2007.