Incidence and predictors of first line antiretroviral regimen modification in western Kenya

Seth Inzaule, Juliana Otieno, Joan Kalyango, Lillian Nafisa, Charles Kabugo, Josephine Nalusiba, Daniel Kwaro, Clement Zeh, Charles Karamagi, Seth Inzaule, Juliana Otieno, Joan Kalyango, Lillian Nafisa, Charles Kabugo, Josephine Nalusiba, Daniel Kwaro, Clement Zeh, Charles Karamagi

Abstract

Background: Limited antiretroviral treatment regimens in resource-limited settings require long-term sustainability of patients on the few available options. We evaluated the incidence and predictors of combined antiretroviral treatment (cART) modifications, in an outpatient cohort of 955 patients who initiated cART between January 2009 and January 2011 in western Kenya.

Methods: cART modification was defined as either first time single drug substitution or switch. Incidence rates were determined by Poisson regression and risk factor analysis assessed using multivariate Cox regression modeling.

Results: Over a median follow-up period of 10.7 months, 178 (18.7%) patients modified regimens (incidence rate (IR); 18.6 per 100 person years [95% CI: 16.2-21.8]). Toxicity was the most common cited reason (66.3%). In adjusted multivariate Cox piecewise regression model, WHO disease stage III/IV (aHR; 1.82, 95%CI: 1.25-2.66), stavudine (d4T) use (aHR; 2.21 95%CI: 1.49-3.30) and increase in age (aHR; 1.02, 95%CI: 1.0-1.04) were associated with increased risk of treatment modification within the first year post-cART. Zidovudine (AZT) and tenofovir (TDF) use had a reduced risk for modification (aHR; 0.60 95%CI: 0.38-0.96 and aHR; 0.51 95%CI: 0.29-0.91 respectively). Beyond one year of treatment, d4T use (aHR; 2.75, 95% CI: 1.25-6.05), baseline CD4 counts ≤350 cells/mm3 (aHR; 2.45, 95%CI: 1.14-5.26), increase in age (aHR; 1.05 95%CI: 1.02-1.07) and high baseline weight >60kg aHR; 2.69 95% CI: 1.58-4.59) were associated with risk of cART modification.

Conclusions: Early treatment initiation at higher CD4 counts and avoiding d4T use may reduce treatment modification and subsequently improve sustainability of patients on the available limited options.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Kaplan Meier plots showing time…
Figure 1. Kaplan Meier plots showing time to cART modification:overall and by key reasons of cART modifications.

References

    1. WHO (2008) Towards Universal Access: Scaling up priority HIV/AIDS interventions in the health sector. In: WHO, Geneva.
    1. UNAIDS (2012) UNAIDS World AIDS Day Report 2012: Results.
    1. UNAIDS (2009) Global Report Fact Sheet. 2009
    1. Kebba A (2003) Antiretroviral therapy in sub-Saharan Africa: myth or reality? J Antimicrob Chemother 52: 747–749.
    1. UNAIDS (2011) UNAIDS World AIDS Day Report 2011: How to get to zero.
    1. WHO (2010) Antiretroviral Therapy for HIV Infection in Adults and Adolescents: Recommendations for a public health approach 2010 revision.
    1. Vo TT, Ledergerber B, Keiser O, Hirschel B, Furrer H, et al. (2008) Durability and outcome of initial antiretroviral treatments received during 2000–2005 by patients in the Swiss HIV Cohort Study. J Infect Dis 197: 1685–1694.
    1. Takuva S, Louwagie G, Khangelani Z, Okello V (2012) Durability of first line antivretroviral therapy: Reasons and predictive factors for modifications in a swaziland cohort. Journal of Antivirals and Antiretrovirals 4: 014–020.
    1. Mocroft A, Youle M, Moore A, Sabin CA, Madge S, et al. (2001) Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre. AIDS 15: 185–194.
    1. Kumarasamy N, Vallabhaneni S, Cecelia AJ, Yepthomi T, Balakrishnan P, et al. (2006) Reasons for modification of generic highly active antiretroviral therapeutic regimens among patients in southern India. J Acquir Immune Defic Syndr 41: 53–58.
    1. Kiguba R, Byakika-Tusiime J, Karamagi C, Ssali F, Mugyenyi P, et al. (2007) Discontinuation and modification of highly active antiretroviral therapy in HIV-infected Ugandans: prevalence and associated factors. J Acquir Immune Defic Syndr 45: 218–223.
    1. Davidson I, Beardsell H, Smith B, Mandalia S, Bower M, et al. (2010) The frequency and reasons for antiretroviral switching with specific antiretroviral associations: the SWITCH study. Antiviral Res 86: 227–229.
    1. Cesar C, Shepherd BE, Krolewiecki AJ, Fink VI, Schechter M, et al. (2010) Rates and reasons for early change of first HAART in HIV-1-infected patients in 7 sites throughout the Caribbean and Latin America. PLoS One 5: e10490.
    1. Braitstein P, Ayuo P, Mwangi A, Wools-Kaloustian K, Musick B, et al. (2010) Sustainability of first-line antiretroviral regimens: findings from a large HIV treatment program in western Kenya. J Acquir Immune Defic Syndr 53: 254–259.
    1. Hammer SM, Eron JJ, Reiss P (2008) Schooley RT, Thompson MA, et al (2008) Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. Jama 300: 555–570.
    1. Calmy A, Ford N, Hirschel B, Reynolds SJ, Lynen L, et al. (2007) HIV viral load monitoring in resource-limited regions: optional or necessary? Clin Infect Dis 44: 128–134.
    1. Hawkins C, Achenbach C, Fryda W, Ngare D, Murphy R (2007) Antiretroviral durability and tolerability in HIV-infected adults living in urban Kenya. J Acquir Immune Defic Syndr 45: 304–310.
    1. Oluoch T, Mohammed I, Bunnell R, Kaiser R, Kim AA, et al. (2011) Correlates of HIV Infection among Sexually Active Adults in Kenya: A National Population-Based Survey. Open AIDS J 5: 125–134.
    1. Abimanyi-Ochom J (2011) The better the worse: risk factors for HIV infection among women in Kenya and Uganda: demographic and health survey. AIDS Care 23: 1545–1550.
    1. NASCOP (2008) Guidelines for antiretroviral therapy in Kenya.
    1. Sterne JA, White IR, Carlin JB, Spratt M, Royston P, et al. (2009) Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. Bmj 338: b2393.
    1. Rubin DB (1987) Multiple imputation for Nonresponse in surveys. New York, NY: J Wiley & Sons.
    1. Messou E, Anglaret X, Duvignac J, Konan-N'dri E, Komena E, et al. (2010) Antiretroviral treatment changes in adults from Cote d'Ivoire: the roles of tuberculosis and pregnancy. AIDS 24: 93–99.
    1. Elzi L, Marzolini C, Furrer H, Ledergerber B, Cavassini M, et al. (2010) Treatment modification in human immunodeficiency virus-infected individuals starting combination antiretroviral therapy between 2005 and 2008. Arch Intern Med 170: 57–65.
    1. Dieleman JP, Jambroes M, Gyssens IC, Sturkenboom MC, Stricker BH, et al. (2002) Determinants of recurrent toxicity-driven switches of highly active antiretroviral therapy. The ATHENA cohort. AIDS 16: 737–745.
    1. The Australian HIV Observational Database (2002) Rates of combination antiretroviral treatment change in Australia, 1997–2000. HIV Med 3: 28–36.
    1. Cicconi P, Cozzi-Lepri A, Castagna A, Trecarichi EM, Antinori A, et al. (2010) Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-naive patients. HIV Med 11: 104–113.
    1. Van Griensven J, De Naeyer L, Mushi T, Ubarijoro S, Gashumba D, et al. (2007) High prevalence of lipoatrophy among patients on stavudine-containing first-line antiretroviral therapy regimens in Rwanda. Trans R Soc Trop Med Hyg 101: 793–798.
    1. Subbaraman R, Chaguturu SK, Mayer KH, Flanigan TP, Kumarasamy N (2007) Adverse effects of highly active antiretroviral therapy in developing countries. Clin Infect Dis 45: 1093–1101.
    1. Mutimura E, Stewart A, Rheeder P, Crowther NJ (2007) Metabolic function and the prevalence of lipodystrophy in a population of HIV-infected African subjects receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr 46: 451–455.
    1. McComsey GA, Lo Re V, O'Riordan M, Walker UA, Lebrecht D, et al. (2008) Effect of reducing the dose of stavudine on body composition, bone density, and markers of mitochondrial toxicity in HIV-infected subjects: a randomized, controlled study. Clin Infect Dis 46: 1290–1296.
    1. Bolhaar MG, Karstaedt AS (2007) A high incidence of lactic acidosis and symptomatic hyperlactatemia in women receiving highly active antiretroviral therapy in Soweto, South Africa. Clin Infect Dis 45: 254–260.
    1. Rosen S, Long L, Fox M, Sanne I (2008) Cost and cost-effectiveness of switching from stavudine to tenofovir in first-line antiretroviral regimens in South Africa. J Acquir Immune Defic Syndr 48: 334–344.
    1. Maskew M, Westreich D, Fox MP, Maotoe T, Sanne IM (2012) Effectiveness and safety of 30 mg versus 40 mg stavudine regimens: a cohort study among HIV-infected adults initiating HAART in South Africa. J Int AIDS Soc 15: 13.
    1. Breen RA, Lipman MC, Johnson MA (2000) Increased incidence of peripheral neuropathy with co-administration of stavudine and isoniazid in HIV-infected individuals. AIDS 14: 615.
    1. Kalyesubula R, Perazella MA (2011) Nephrotoxicity of HAART. AIDS Res Treat: 562790.
    1. Rawizza HE, Chaplin B, Meloni ST, Eisen G, Rao T, et al. (2011) Immunologic criteria are poor predictors of virologic outcome: implications for HIV treatment monitoring in resource-limited settings. Clin Infect Dis 53: 1283–1290.
    1. Kantor R, Diero L, Delong A, Kamle L, Muyonga S, et al. (2009) Misclassification of first-line antiretroviral treatment failure based on immunological monitoring of HIV infection in resource-limited settings. Clin Infect Dis 49: 454–462.
    1. WHO (2013) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: Recommendations for a public health approach.
    1. Van Griensven J, Zachariah R, Rasschaert F, Mugabo J, Atte EF, et al. (2010) Stavudine- and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment: incidence, timing and risk factors in a three-year cohort in Kigali, Rwanda. Trans R Soc Trop Med Hyg 104: 148–153.
    1. Boulle A, Orrel C, Kaplan R, Van Cutsem G, McNally M, et al. (2007) Substitutions due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral therapy in a large South African cohort. Antivir Ther 12: 753–760.
    1. Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, et al. (2009) Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 360: 1815–1826.
    1. Johansson KA, Robberstad B, Norheim OF (2010) Further benefits by early start of HIV treatment in low income countries: survival estimates of early versus deferred antiretroviral therapy. AIDS Res Ther 7: 3.
    1. El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, et al. (2006) CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 355: 2283–2296.
    1. Anand A, Shiraishi RW, Bunnell RE, Jacobs K, Solehdin N, et al. (2009) Knowledge of HIV status, sexual risk behaviors and contraceptive need among people living with HIV in Kenya and Malawi. AIDS 23: 1565–1573.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere