AIDS Research and Human Retroviruses 2014.30:623-625. Downloaded from online.liebertpub.com by Ucsd Libraries University of California San Diego on 01/06/15. For personal use only.

AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 30, Number 7, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/aid.2014.0035

LETTER TO THE EDITOR

Challenges of Antiretroviral Treatment Monitoring in Rural and Remote-Access Regions in Africa Fabien Taieb,1,2 Avelin F. Aghokeng,2,3 Sabrina Eymard-Duvernay,2 Julius Ebua Chia,3 Ellen Einterz,4 Eitel Mpoudi-Ngole,3 Martine Peeters,2 Jean-Michel Molina,1 and Eric Delaporte 2

E

ditor: The 2013 United Nations Program on HIV/AIDS (UNIAIDS) Report on the global HIV/AIDS epidemic highlighted significant progress toward the elimination of HIV infection. Key achievements included a major decline in HIV-related deaths over the past 20 years, an almost 35% decline in the number of new infections between 2000 and 2012, and an important increase in the availability of antiretroviral treatment (ART), with more than 50% of the people in need of treatment receiving it.1 While acknowledging this progress, it is also very important to emphasize the fact that in 2012, about 1.6 million people died of HIV-related causes,1 and the current global achievements are not uniform across countries, in level of programs in countries (e.g., urban and rural), and in population groups, including newborns.2,3 Indeed, our experience from the field may contribute to that global vision, by providing more country- and contextspecific data. In addition to the increase in ART coverage, virologic suppression in patients receiving antiretrovirals (ARVs), predominantly first-line regimens, is globally indicated as good, from 70% to 90% after 6 months to 24 months of ART.4 However, several recent reports on the extent of HIV drug resistance (HIVDR) among adults who fail firstline ART have also indicated a significant accumulation of drug resistance mutations (DRMs), with potential consequences concerning the efficacy of second-line regimes.5,6 These findings are, however, generally limited to urban areas and major cities in Africa, and only in a small number of cases do reports cover remote rural regions, in which an increased proportion of patients is now receiving ART. In fact, both levels are generally not comparable in terms of infrastructure and resources, with rural areas characterized by higher rates of poverty, lower literacy rates, longer distances to healthcare facilities, and often higher levels of food insecurity and malnutrition. This description is close to that of the District of Kolofata in the extreme north of Cameroon, WestCentral Africa, which is located 1,200 km from the capital city Yaounde´, has one doctor for 120,000 inhabitants, and in which the literacy rate is around 10%. The District Hospital of Kolofata started providing ART in 2007, following the national decentralization process of the ART program initiated in early 2007 in Cameroon. The hospital had one med-

ical doctor and the majority of clinical activities was managed by nurses. The site was providing care to about 350 HIV-1-infected patients at the end of 2011, and 193 were receiving ART. In this rural hospital between 2009 and 2011 we conducted a cross-sectional study to access the virologic outcome and the frequency of drug-resistant viruses among patients receiving first-line ART for over 12 months. We collected demographic and clinical data including age, gender, occupation, WHO clinical stage,7 ARV regimen, and information on previous exposure to ARVs. We obtained a written consent from all study participants before enrollment and the Cameroon National Ethics Committee approved the study. We collected dried blood spots (DBS) and shipped them to a reference WHO laboratory in the capital city Yaounde´, where they were used for viral load (VL) testing and drug resistance genotyping as previously reported.8,9 We considered virologic failure as VL ‡ 1,000 copies/ml. Overall, 155 patients were enrolled. Ninety-six patients (62%) were women and the median age (interquartile range) was 37 years (30–45). The median duration under ART (interquartile range) was 24 months (12–36). One hundred and forty-three of the 155 patients (92.3%) were at WHO stage 1 or 2 and the CD4 + T cell count was not available in the hospital. All were receiving a first-line ARV regimen recommended at that time by the national ART program, essentially lamivudine plus stavudine or zidovudine plus nevirapine or efavirenz, and 37/155 patients (24%) reported the use of traditional medicines in addition to their routine ART. Fifty-four patients had VL ‡ 1,000 copies/ml, leading to an overall virologic failure rate of 38.6%. Among those patients who failed, the frequency of drug-resistant virus was 75.0%. Not surprisingly, resistance mutations to low genetic barrier nonnucleoside reverse transcriptase inhibitors (NNRTIs) were found in all resistant viruses. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs) or to both drug classes was found in 80% of patients with resistant virus. In addition, viruses accumulated several mutations to both drug classes. The direct consequence of the accumulation of DRMs is that other drugs not included in the first-line therapy may

1

Hoˆpital Saint-Louis, Service de Maladies Infectieuses et Tropicales, Paris, France. UMI 233 TransVIHMI, Institut de Recherche pour le De´veloppement (IRD), University Montpellier 1, Montpellier, France. Virology Laboratory CREMER/IMPM/IRD, Yaounde´, Cameroon. 4 District Hospital, Kolofata, Cameroon. 2 3

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become less effective if utilized in the second-line regimen, and in our study, several drugs such as abacavir (found in 6 individuals), didanosine (found in 5 individuals), tenofovir (found in 4 individuals), etravirine (found in 9 individuals), and rilpivirine (found in 13 individuals) were subject to reduced efficacy in patients who never received them. That result is not specific to rural areas and several studies described an accumulation of DRMs among patients failing ART in various African settings.10,11 However, for national ART programs with limited resources, managing such complex cases might be highly challenging in rural regions where treatment options are generally very limited and biological monitoring is not available. Recent studies in an urban region of Cameroon have reported virologic failure rates around 10% for patients receiving first-line ART after 12 to 24 months,12 and the failure rate we found in this rural hospital was close to 40%, indicating a significant difference in treatment outcome between both healthcare levels. Although the present report describes the situation in only one particular site and cannot be generalized to the whole country, it indicates, however, that the outcome of ART in remote rural regions in Cameroon may be significantly bad. In addition, these results concurred with those from other rural settings in Africa, as recently reported from rural Gabon where virologic failure after a median of 33.6 months of ART was 41.3% (36.4–46.4%).13 A 2012 report on the outcome of ART programs in rural southern Africa, Lesotho, Mozambique, and Zimbabwe showed high levels of mortality and loss to follow-up in the first 3 years of ART.2 The limited capacity of the healthcare systems in these rural regions is of great concern and partly explains the poor quality of ART outcome. In Cameroon, as in many African countries, monitoring of viral load is not routinely provided in either urban or rural areas and thus the lack of virologic monitoring is not the only justification for the poor outcome of ART. In many countries, extension of access to ART to remote rural regions was not always accompanied by adequate reinforcement of healthcare and support staff, laboratory infrastructures, and/or adapter supply chains for commodities and drugs. As a consequence, the current leading cause of virologic failure is poor adherence, which is amplified when additional catalysts such as poor retention and drug stock-outs are not prevented. Indeed, a recent assessment of programmatic indicators of the Cameroonian ART program showed poor outcomes for key targets such as loss to follow-up, on-time drug pick-up, and drug stock-outs, which may favor treatment failure and drug resistance, especially in remote-access and rural regions.14 Also, studies assessing the outcome of ART in rural Africa are still scarce and this needs to be improved. Because the urban environment and rural environment are not similar, it is obvious that specific strategies for access to ART and monitoring should be developed for rural regions and tailored to local contexts. Home-based and/or community-based interventions, as well as peer support groups already well implemented in some southern African regions,15,16 should be coupled with the conventional clinic-based strategy when dealing with rural regions. The attainment of zero HIV deaths is an ambitious goal that needs to be achieved in the near future, but meeting this target will require both global and context-specific assessments and interventions to address major challenges. Improving access to ART, improving its

LETTER TO THE EDITOR

outcome, and improving the quality of disease monitoring in rural settings in RLC are some of these challenges. Acknowledgments

We thank all patients who kindly agreed to participate in this study as well as the medical staffs and the Ministry of Public Health of Cameroon. This work was supported by the Institut de Recherche pour le De´veloppement (IRD). Author Disclosure Statement

No competing financial interests exist. References

1. UNAIDS (2013): Report on the global AIDS epidemic 2013. www.unaids.org/en/media/unaids/contentassets/documents/ epidemiology/2013/gr2013/UNAIDS_Global_Report_2013 _en.pdf. Accessed January 23, 2014. 2. Wandeler G, Keiser O, et al.: Outcomes of antiretroviral treatment programs in rural Southern Africa. J Acquir Immune Defic Syndr 2012;59(2):e9–16. 3. Kebe K, Thiam M, et al.: High rate of antiretroviral drug resistance mutations in HIV type 1-infected Senegalese children in virological failure on first-line treatment according to the World Health Organization guidelines. AIDS Res Hum Retroviruses 2013;29(2):242–249. 4. Barth RE, van der Loeff MF, et al.: Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: A systematic review. Lancet Infect Dis 2010;10(3):155–166. 5. Sigaloff KC, Ramatsebe T, et al.: Accumulation of HIV drug resistance mutations in patients failing first-line antiretroviral treatment in South Africa. AIDS Res Hum Retroviruses 2012;28(2):171–175. 6. Aghokeng AF, Kouanfack C, et al.: Virological outcome and patterns of HIV-1 drug resistance in patients with 36 months’ antiretroviral therapy experience in Cameroon. J Int AIDS Soc 2013;16:18004. 7. WHO (2010): Antiretroviral therapy for HIV infection in adults and adolescents. Recommendations for a public health approach: 2010 revision. whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf. Accessed November 1, 2011. 8. Arredondo M, Garrido C, et al.: Comparison of HIV-1 RNA measurements obtained by using plasma and dried blood spots in the automated Abbott real-time viral load assay. J Clin Microbiol 2012;50(3):569–572. 9. Monleau M, Aghokeng AF, et al.: Field evaluation of dried blood spots (DBS) for routine HIV-1 viral load and drug resistance monitoring in patients receiving antiretroviral therapy in Africa and Asia. J Clin Microbiol 2014;52(2): 578–586. 10. Dagnra AY, Vidal N, et al.: High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lome, Togo. J Int AIDS Soc 2011;14:30. 11. Pere H, Charpentier C, et al.: Virological response and resistance profiles after 24 months of first-line antiretroviral treatment in adults living in Bangui, Central African Republic. AIDS Res Hum Retroviruses 2012;28(4): 315–323. 12. Aghokeng AF, Monleau M, et al.: Extraordinary heterogeneity of virological outcomes in patients receiving highly active antiretroviral therapy and monitored with the World

AIDS Research and Human Retroviruses 2014.30:623-625. Downloaded from online.liebertpub.com by Ucsd Libraries University of California San Diego on 01/06/15. For personal use only.

LETTER TO THE EDITOR

Health Organization public health approach in sub-Saharan Africa and southeast Asia. Clin Infect Dis 2014;58(1):99– 109. 13. Liegeois F, Vella C, et al.: Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon. J Int AIDS Soc 2012;15(2):17985. 14. Billong SC, Fokam J, et al.: Early warning indicators for HIV drug resistance in Cameroon during the year 2010. PLoS One 2012;7(5):e36777. 15. Bedelu M, Ford N, et al.: Implementing antiretroviral therapy in rural communities: The Lusikisiki model of decentralized HIV/AIDS care. J Infect Dis 2007;196(Suppl 3):S464–468.

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16. Decroo T, Telfer B, et al.: Distribution of antiretroviral treatment through self-forming groups of patients in Tete Province, Mozambique. J Acquir Immune Defic Syndr 2011;56(2):e39–44.

Address correspondence to: Avelin F. Aghokeng Virology Laboratory CREMER/IMPM/IRD Rue Elig-Essono P.O. Box 1857 Yaounde´ 1857 Cameroon E-mail: [email protected]

Challenges of antiretroviral treatment monitoring in rural and remote-access regions in Africa.

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