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Published in: BMC Infectious Diseases 1/2019

Open Access 01-12-2019 | Care | Research article

Retention in care and virological failure among adult HIV+ patients on second-line ART in Rwanda: a national representative study

Authors: Sabin Nsanzimana, Muhammed Semakula, Vedaste Ndahindwa, Eric Remera, Dieudonne Sebuhoro, Jean Paul Uwizihiwe, Nathan Ford, Marcel Tanner, Steve Kanters, Edward J. Mills, Heiner C. Bucher

Published in: BMC Infectious Diseases | Issue 1/2019

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Abstract

Background

Currently, there is limited evidence on the effectiveness of second-line antiretroviral therapy (ART) in sub-Saharan Africa. To address this challenge, outcomes of second-line protease inhibitor (PI) based ART in Rwanda were assessed.

Methods

A two-stage cluster sampling design was undertaken. 49 of 340 health facilities linked to the open-source electronic medical record (EMR) system of Rwanda were randomly sampled. Data sampling criteria included adult HIV positive patients with documented change from first to second-line ART regimen. Retention in care and treatment failure (viral load above 1000 copies/mL) were evaluated using multivariable Cox proportional hazards and logistic regression models.

Results

A total of 1688 patients (60% females) initiated second-line ART PI-based regimen by 31st December 2016 with a median follow-up time of 26 months (IQR 24–36). Overall, 92.5% of patients were retained in care; 83% achieved VL ≤ 1000 copies/ml, 2.8% were lost to care and 2.2% died. Defaulting from care was associated with more recent initiation of ART- PI based regimen, CD4 cell count ≤500 cells/mm3 at initiation of second line ART and viral load > 1000 copies/ml at last measurement. Viral failure was associated with younger age, WHO stage III&IV at ART initiation, CD4 cell count ≤500 cells/mm3 at switch, atazanavir based second-line ART and receiving care at a health center compared to hospital settings.

Conclusions

A high proportion of patients on second-line ART are doing relatively well in Rwanda and retained in care with low viral failure rates. However, enhanced understandings of adherence and adherence interventions for less healthy individuals are required. Routine viral load measurement and tracing of loss to follow-up is fundamental in resource limited settings, especially among less healthy patients.
Literature
1.
2.
3.
go back to reference Kharsany ABM. Karim QA. HIV Infection and AIDS in Sub-Saharan Africa: Current Status. 2016:34–48. Kharsany ABM. Karim QA. HIV Infection and AIDS in Sub-Saharan Africa: Current Status. 2016:34–48.
4.
go back to reference Haas AD, Keiser O, Balestre E, Brown S, Bissagnene E, Chimbetete C, et al. Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis. Lancet HIV. 2015;2(7):e271–8.CrossRef Haas AD, Keiser O, Balestre E, Brown S, Bissagnene E, Chimbetete C, et al. Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis. Lancet HIV. 2015;2(7):e271–8.CrossRef
5.
go back to reference Care P. First-line antiretroviral treatment failure and associated factors in HIV patients at the University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia; 2016. p. 141–6. Care P. First-line antiretroviral treatment failure and associated factors in HIV patients at the University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia; 2016. p. 141–6.
6.
go back to reference World Health Organization. The use of antiretroviral drugs for treating and preventing hiv infection. 2016. World Health Organization. The use of antiretroviral drugs for treating and preventing hiv infection. 2016.
7.
go back to reference Hosseinipour MC, Gupta RK, Zyl G Van, Eron JJ, Nachega JB. Emergence of HIV Drug Resistance During First- and Second-Line Antiretroviral Therapy in Resource-Limited Settings. J Infect Dis. 2013;207(Suppl 2):S49–56. Hosseinipour MC, Gupta RK, Zyl G Van, Eron JJ, Nachega JB. Emergence of HIV Drug Resistance During First- and Second-Line Antiretroviral Therapy in Resource-Limited Settings. J Infect Dis. 2013;207(Suppl 2):S49–56.
8.
go back to reference Laurent C, Kouanfack C, Laborde-Balen G, Aghokeng AF, Mbougua JBT, Boyer S, et al. Monitoring of HIV viral loads, CD4 cell counts, and clinical assessments versus clinical monitoring alone for antiretroviral therapy in rural district hospitals in Cameroon (Stratall ANRS 12110/ESTHER): a randomised non-inferiority trial. Lancet Infect Dis. 2011;11(11):825–33.CrossRef Laurent C, Kouanfack C, Laborde-Balen G, Aghokeng AF, Mbougua JBT, Boyer S, et al. Monitoring of HIV viral loads, CD4 cell counts, and clinical assessments versus clinical monitoring alone for antiretroviral therapy in rural district hospitals in Cameroon (Stratall ANRS 12110/ESTHER): a randomised non-inferiority trial. Lancet Infect Dis. 2011;11(11):825–33.CrossRef
9.
go back to reference Nsanzimana S, Kanters S, Remera E, Forrest JI, Binagwaho A, Condo J, et al. Articles HIV care continuum in Rwanda: a cross-sectional analysis of the national programme; 2013. p. 208–15. Nsanzimana S, Kanters S, Remera E, Forrest JI, Binagwaho A, Condo J, et al. Articles HIV care continuum in Rwanda: a cross-sectional analysis of the national programme; 2013. p. 208–15.
10.
go back to reference Wilhelmson S, Reepalu A, Balcha TT, Jarso G, Björkman P. Retention in care among HIV-positive patients initiating second-line antiretroviral therapy: a retrospective study from an Ethiopian public hospital clinic. Glob Health Action. 2016;9(1):1–8.CrossRef Wilhelmson S, Reepalu A, Balcha TT, Jarso G, Björkman P. Retention in care among HIV-positive patients initiating second-line antiretroviral therapy: a retrospective study from an Ethiopian public hospital clinic. Glob Health Action. 2016;9(1):1–8.CrossRef
11.
go back to reference Sherr K, Pfeiffer J, Mussa A, Vio F, Gimbel S, Micek M, et al. The role of nonphysician clinicians in the rapid expansion of HIV Care in Mozambique. JAIDS J Acquir Immune Defic Syndr. 2009;52:S20–3.CrossRef Sherr K, Pfeiffer J, Mussa A, Vio F, Gimbel S, Micek M, et al. The role of nonphysician clinicians in the rapid expansion of HIV Care in Mozambique. JAIDS J Acquir Immune Defic Syndr. 2009;52:S20–3.CrossRef
12.
go back to reference Bartlett JA, Shao JF. Successes, challenges, and limitations of current antiretroviral therapy in low-income and middle-income countries. Lancet Infect Dis. 2009;9(10):637–49.CrossRef Bartlett JA, Shao JF. Successes, challenges, and limitations of current antiretroviral therapy in low-income and middle-income countries. Lancet Infect Dis. 2009;9(10):637–49.CrossRef
13.
go back to reference Shao Y, Williamson C. The HIV-1 epidemic: low- to middle-income countries. Cold Spring Harb Perspect Med. 2012;2(3):–a007187. Shao Y, Williamson C. The HIV-1 epidemic: low- to middle-income countries. Cold Spring Harb Perspect Med. 2012;2(3):–a007187.
14.
go back to reference Nsanzimana S, Kanters S, Remera E, Forrest JI, Binagwaho A, Condo J, et al. HIV care continuum in Rwanda : a cross-sectional analysis of the national programme. Lancet HIV. 2015;3018(15):1–8. Nsanzimana S, Kanters S, Remera E, Forrest JI, Binagwaho A, Condo J, et al. HIV care continuum in Rwanda : a cross-sectional analysis of the national programme. Lancet HIV. 2015;3018(15):1–8.
15.
go back to reference World Health Organization (WHO). Patient monitoring guidelines for HIV care and antiretroviral therapy (ART). 2006. World Health Organization (WHO). Patient monitoring guidelines for HIV care and antiretroviral therapy (ART). 2006.
16.
go back to reference Shearer K, Evans D, Moyo F, Rohr JK, Berhanu R, Van Den Berg L, et al. Treatment outcomes of over 1000 patients on second-line, protease inhibitor-based antiretroviral therapy from four public-sector HIV treatment facilities across Johannesburg, South Africa. Trop Med Int Heal. 2017;22(2):221–31.CrossRef Shearer K, Evans D, Moyo F, Rohr JK, Berhanu R, Van Den Berg L, et al. Treatment outcomes of over 1000 patients on second-line, protease inhibitor-based antiretroviral therapy from four public-sector HIV treatment facilities across Johannesburg, South Africa. Trop Med Int Heal. 2017;22(2):221–31.CrossRef
17.
go back to reference Assefa Y, Kiflie A, Tesfaye D, Mariam DH, Kloos H, Edwin W, et al. Outcomes of antiretroviral treatment program in Ethiopia: Retention of patients in care is a major challenge and varies across health facilities. BMC Health Serv Res. 2011;11(1):81.CrossRef Assefa Y, Kiflie A, Tesfaye D, Mariam DH, Kloos H, Edwin W, et al. Outcomes of antiretroviral treatment program in Ethiopia: Retention of patients in care is a major challenge and varies across health facilities. BMC Health Serv Res. 2011;11(1):81.CrossRef
18.
go back to reference d’Amour NJ, Riedel DJ, Mwumvaneza M, Sebuhoro D, Uwimbabazi JC, Kubwimana M, et al. Drug resistance mutations after the first 12 months on antiretroviral therapy and determinants of virological failure in Rwanda. Trop Med Int Heal. 2016;21(7):928–35.CrossRef d’Amour NJ, Riedel DJ, Mwumvaneza M, Sebuhoro D, Uwimbabazi JC, Kubwimana M, et al. Drug resistance mutations after the first 12 months on antiretroviral therapy and determinants of virological failure in Rwanda. Trop Med Int Heal. 2016;21(7):928–35.CrossRef
19.
go back to reference Ajose O, Mookerjee S, Mills EJ, Boulle A, Ford N. Treatment outcomes of patients on second-line antiretroviral therapy in resource-limited settings. AIDS. 2012;26(8):929–38.CrossRef Ajose O, Mookerjee S, Mills EJ, Boulle A, Ford N. Treatment outcomes of patients on second-line antiretroviral therapy in resource-limited settings. AIDS. 2012;26(8):929–38.CrossRef
20.
go back to reference Boettiger DC, Nguyen VK, Durier N, Bui HV, Heng Sim BL, Azwa I, et al. Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia. JAIDS J Acquir Immune Defic Syndr. 2015;68(2):186–95.CrossRef Boettiger DC, Nguyen VK, Durier N, Bui HV, Heng Sim BL, Azwa I, et al. Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia. JAIDS J Acquir Immune Defic Syndr. 2015;68(2):186–95.CrossRef
21.
go back to reference Hosseinipour M, Kumwenda J, Weigel R, Brown L, Mzinganjira D, Mhango B, et al. Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline. HIV Med. 2010;11(8):510–8.PubMedPubMedCentral Hosseinipour M, Kumwenda J, Weigel R, Brown L, Mzinganjira D, Mhango B, et al. Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline. HIV Med. 2010;11(8):510–8.PubMedPubMedCentral
22.
go back to reference Win MM, Maek-a-nantawat W, Phonrat B, Kiertiburanakul S, Sungkanuparph S. Virologic and Immunologic Outcomes of the Second-Line Regimens of Antiretroviral Therapy Among HIV-Infected Patients in Thailand. J Int Assoc Physicians AIDS Care. 2011;10(1):57–63.CrossRef Win MM, Maek-a-nantawat W, Phonrat B, Kiertiburanakul S, Sungkanuparph S. Virologic and Immunologic Outcomes of the Second-Line Regimens of Antiretroviral Therapy Among HIV-Infected Patients in Thailand. J Int Assoc Physicians AIDS Care. 2011;10(1):57–63.CrossRef
23.
go back to reference Wilhelmson S, Reepalu A, Tolera Balcha T, Jarso G, Björkman P. Retention in care among HIV-positive patients initiating second-line antiretroviral therapy: a retrospective study from an Ethiopian public hospital clinic. Glob Health Action. 2016;9(1):29943.CrossRef Wilhelmson S, Reepalu A, Tolera Balcha T, Jarso G, Björkman P. Retention in care among HIV-positive patients initiating second-line antiretroviral therapy: a retrospective study from an Ethiopian public hospital clinic. Glob Health Action. 2016;9(1):29943.CrossRef
24.
go back to reference Fox MP, Ive P, Long L, Maskew M, Sanne I. High rates of survival, immune reconstitution, and Virologic suppression on second-line antiretroviral therapy in South Africa. JAIDS J Acquir Immune Defic Syndr. 2010;53(4):500–6.CrossRef Fox MP, Ive P, Long L, Maskew M, Sanne I. High rates of survival, immune reconstitution, and Virologic suppression on second-line antiretroviral therapy in South Africa. JAIDS J Acquir Immune Defic Syndr. 2010;53(4):500–6.CrossRef
25.
go back to reference Kanters S, Socias ME, Paton NI, Vitoria M, Doherty M, Ayers D, et al. Comparative efficacy and safety of second-line antiretroviral therapy for treatment of HIV/AIDS: a systematic review and network meta-analysis. Lancet HIV. 2017;4(10):e433–41.CrossRef Kanters S, Socias ME, Paton NI, Vitoria M, Doherty M, Ayers D, et al. Comparative efficacy and safety of second-line antiretroviral therapy for treatment of HIV/AIDS: a systematic review and network meta-analysis. Lancet HIV. 2017;4(10):e433–41.CrossRef
26.
go back to reference Laker E, Mambule I, Nalwanga D, Musaazi J, Kiragga A, Parkes-Ratanshi R. Boosted lopinavir vs boosted atazanavir in patients failing a NNRTI first line regimen in an urban clinic in Kampala. J Int AIDS Soc. 2014;17:19792.CrossRef Laker E, Mambule I, Nalwanga D, Musaazi J, Kiragga A, Parkes-Ratanshi R. Boosted lopinavir vs boosted atazanavir in patients failing a NNRTI first line regimen in an urban clinic in Kampala. J Int AIDS Soc. 2014;17:19792.CrossRef
27.
go back to reference Ongubo DM, Lim R, Tweya H, Stanley CC, Tembo P, Broadhurst R, et al. A cross-sectional study to evaluate second-line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe. Malawi BMC Infect Dis. 2017;17(1):461.CrossRef Ongubo DM, Lim R, Tweya H, Stanley CC, Tembo P, Broadhurst R, et al. A cross-sectional study to evaluate second-line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe. Malawi BMC Infect Dis. 2017;17(1):461.CrossRef
28.
go back to reference Smith D, Jeganathan S, Ray J. Atazanavir plasma concentrations vary significantly between patients and correlate with increased serum bilirubin concentrations. HIV Clin Trials. 2006;7(1):34–8.CrossRef Smith D, Jeganathan S, Ray J. Atazanavir plasma concentrations vary significantly between patients and correlate with increased serum bilirubin concentrations. HIV Clin Trials. 2006;7(1):34–8.CrossRef
29.
go back to reference Jobanputra K, Parker LA, Azih C, Okello V, Maphalala G, Kershberger B, et al. Factors Associated with Virological Failure and Suppression after Enhanced Adherence Counselling, in Children, Adolescents and Adults on Antiretroviral Therapy for HIV in Swaziland. Paraskevis D, editor. PLoS One. 2015;10(2):e0116144. Jobanputra K, Parker LA, Azih C, Okello V, Maphalala G, Kershberger B, et al. Factors Associated with Virological Failure and Suppression after Enhanced Adherence Counselling, in Children, Adolescents and Adults on Antiretroviral Therapy for HIV in Swaziland. Paraskevis D, editor. PLoS One. 2015;10(2):e0116144.
30.
go back to reference Johnston V, Fielding KL, Charalambous S, Churchyard G, Phillips A, Grant AD. Outcomes following Virological failure and predictors of switching to second-line antiretroviral therapy in a south African treatment program. JAIDS J Acquir Immune Defic Syndr. 2012;61(3):370–80.CrossRef Johnston V, Fielding KL, Charalambous S, Churchyard G, Phillips A, Grant AD. Outcomes following Virological failure and predictors of switching to second-line antiretroviral therapy in a south African treatment program. JAIDS J Acquir Immune Defic Syndr. 2012;61(3):370–80.CrossRef
31.
go back to reference Wilhelmson S, Reepalu A, Balcha TT, Jarso G, Bjo P. Retention in care among HIV-positive patients initiating second-line antiretroviral therapy: a retrospective study from an Ethiopian public hospital clinic. Glob Health Action. 2016;9:29943. Wilhelmson S, Reepalu A, Balcha TT, Jarso G, Bjo P. Retention in care among HIV-positive patients initiating second-line antiretroviral therapy: a retrospective study from an Ethiopian public hospital clinic. Glob Health Action. 2016;9:29943.
32.
go back to reference Kyaw NTT, Harries AD, Kumar AM V., Oo MM, Kyaw KWY, Win T, et al. High rate of virological failure and low rate of switching to second-line treatment among adolescents and adults living with HIV on first-line ART in Myanmar, 2005–2015. De Socio GV, editor. PLoS One. 2017;12(2):e0171780. Kyaw NTT, Harries AD, Kumar AM V., Oo MM, Kyaw KWY, Win T, et al. High rate of virological failure and low rate of switching to second-line treatment among adolescents and adults living with HIV on first-line ART in Myanmar, 2005–2015. De Socio GV, editor. PLoS One. 2017;12(2):e0171780.
33.
go back to reference Schoffelen AF, Wensing AMJ, Tempelman HA, Geelen SPM, Hoepelman AIM, Barth RE. Sustained Virological Response on Second-Line Antiretroviral Therapy following Virological Failure in HIV-Infected Patients in Rural South Africa. Sluis-Cremer N, editor. PLoS One. 2013;8(3):e58526. Schoffelen AF, Wensing AMJ, Tempelman HA, Geelen SPM, Hoepelman AIM, Barth RE. Sustained Virological Response on Second-Line Antiretroviral Therapy following Virological Failure in HIV-Infected Patients in Rural South Africa. Sluis-Cremer N, editor. PLoS One. 2013;8(3):e58526.
34.
go back to reference Stinson K, Ford N, Cox V, Boulle A. Patients lost to Care are more likely to be Viremic than patients still in Care. Clin Infect Dis. 2014;58(9):1344–5.CrossRef Stinson K, Ford N, Cox V, Boulle A. Patients lost to Care are more likely to be Viremic than patients still in Care. Clin Infect Dis. 2014;58(9):1344–5.CrossRef
35.
go back to reference d’Amour Ndahimana J, Riedel DJ, Muhayimpundu R, Nsanzimana S, Niyibizi G, Mutaganzwa E, et al. HIV drug resistance mutations among patients failing second-line antiretroviral therapy in Rwanda. Antivir Ther. 2015;20(3):253–9.CrossRef d’Amour Ndahimana J, Riedel DJ, Muhayimpundu R, Nsanzimana S, Niyibizi G, Mutaganzwa E, et al. HIV drug resistance mutations among patients failing second-line antiretroviral therapy in Rwanda. Antivir Ther. 2015;20(3):253–9.CrossRef
36.
go back to reference Al-Dakkak I, Patel S, McCann E, Gadkari A, Prajapati G, Maiese EM. The impact of specific HIV treatment-related adverse events on adherence to antiretroviral therapy: a systematic review and meta-analysis. AIDS Care. 2013;25(4):400–14.CrossRef Al-Dakkak I, Patel S, McCann E, Gadkari A, Prajapati G, Maiese EM. The impact of specific HIV treatment-related adverse events on adherence to antiretroviral therapy: a systematic review and meta-analysis. AIDS Care. 2013;25(4):400–14.CrossRef
Metadata
Title
Retention in care and virological failure among adult HIV+ patients on second-line ART in Rwanda: a national representative study
Authors
Sabin Nsanzimana
Muhammed Semakula
Vedaste Ndahindwa
Eric Remera
Dieudonne Sebuhoro
Jean Paul Uwizihiwe
Nathan Ford
Marcel Tanner
Steve Kanters
Edward J. Mills
Heiner C. Bucher
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2019
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-019-3934-2

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