Immuno-haematologic and virologic responses and predictors of virologic failure in HIV-1 infected adults on first-line antiretroviral therapy in Cameroon

Infectious Diseases of Poverty

Theresa Nkuo-Akenji¹  Fidelis Cho-Ngwa³  Damian N Anong³  Pascal N Atanga⁴  Bernard A Nyindem²  Mbunkah H Afegenwi³  Kukwah A Tufon³  Henry D Meriki² 

[1] Faculty of Science Clinical Diagnostic Laboratory, University of Buea, Buea, Cameroon;BioCollections Worldwide Inc. Regional Office, Buea, Cameroon;Department of Microbiology and Parasitology, University of Buea, P.O. Box 63, Buea, Cameroon;Regional Delegation of Public Health, Southwest Region, Cameroon

关键词: Antiretroviral therapy;    Virologic failure;    Predictors;    Immuno-haematologic;   

Others  :  801324
DOI  :  10.1186/2049-9957-3-5

 received in 2013-07-10, accepted in 2014-01-27,  发布年份 2014

【 摘 要 】

Background

Contemporary data on the immunologic, haematologic and virologic responses and predictors of virologic failure after initiation of free antiretroviral treatment in Cameroon are needed to evaluate the current treatment-monitoring algorithm and to complement efforts to scale-up and improve on the management of HIV infections.

Methods

This was a cross-sectional study conducted between October 2010 and June 2012. A total of 951 participants aged 18–74 years were recruited from selected approved HIV treatment centres of the Northwest and Southwest regions. This comprised 247 males and 704 females. Demographic, self-reported risk behaviours and socioeconomic data were obtained using a structured questionnaire. Full blood and CD4 + T-cell counts were done using standard automated techniques. Determination of viral load (VL) was done using Abbott RealTime HIV-1 m2000™ system. Data was analysed using SPSS version 17. The statistical significance level was P < 0.05.

Results

The median duration of antiretroviral therapy (ART) was 24 months. The population mean CD4 + T-cell count was 255.3 cells/μL [95% CI, 236.8 – 273.9]. Overall, 45.9%, 43.8% and 10.2% of the participants had CD4 + T-cell counts of < 200 cells/μL, 200–499 cells/μL and > 500 cells/μL respectively. Anaemia was present in 26.2% of the participants with 62.3%, 25.7% and 12% described as mild, moderate and severe anaemia respectively. Virologic failure occurred in 23.2% of the participants with 12.3% having VL > 10,000 RNA copies/mL. Meanwhile 76.8% of patients attained adequate viral suppression with 40.8% having undetectable viral load. The age group 18–29 years (p = 0.024), co-infection with tuberculosis (p = 0.014), anaemia (p = 0.028) and distance from the treatment centre (p = 0.011) independently predicted virologic failure.

Conclusion

The majority of the participants achieved adequate viral suppression after ≥ 6 months of ART. Despite these favourable immuno-haematologic and virologic outcomes, the National AIDS Control Program should step-up efforts to improve on antiretroviral drug distribution, as well as proper assessment and management of anaemia, foster early diagnosis and treatment of tuberculosis and enhance treatment adherence counselling especially in younger patients.

【 授权许可】

   
2014 Meriki et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Mills E, Nachega J, Buchan I: Adherence to antiretroviral therapy in sub-Saharan Africa and North America. J Am Med Assoc 2006, 296:679-90.
• [2]Crowe S, Turnbull S, Oelrichs R, Dunne A: Monitoring of human immunodeficiency virus infection in resource-constrained countries. Clin Infect Dis 2003, 37:S25-35.
• [3]Metzner KJ, Binley JM, Gettie A, Marx P, Nixon DF, Connor RI: Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques. Retrovirology 2006, 3:97. BioMed Central Full Text
• [4]Omoregie R, Omokaro EU, Palmer O, Ogefere HO, Egbeobauwaye A, Adeghe JE, Osakue SI, Ihemeje V: Prevalence of anaemia among HIV-infected patients in Benin City. Nigeria. Tanzan. J. Health Res. 2009, 11:1-4.
• [5]Gallant JE: Strategies for long-term success in the treatment of HIV infection. J Am Med Assoc 2000, 283:1329-34.
• [6]Haubrich R, Currier J: A randomized study of the utility of human immunodeficiency virus RNA measurement for the management of antiretroviral therapy. Clin Infect Dis 2001, 33:1060-1068.
• [7]WHO: Antiretroviral Therapy for HIV infection in Adults and Adolescents: Recommendations for a public health approach 2006 revision. HIV/AIDS Programme: Strengthening health services to fight HIV/AIDS. Geneva: World Health Organization; 2006.
• [8]Apondi R, Bunnell R, Ekwaru JP, Moore D, Bechange S, Khana K, King R, Campbell J, Tappero J, Mermin J: Sexual behavior and HIV transmission risk of Ugandan adults taking antiretroviral therapy: 3 year follow-up. AIDS 2011, 25:1317-1327.
• [9]Institut National de la Statistique, Ministère de l’Économie de la Planification et de l’Aménagement du Territoire et Ministère de la Santé Publique: Enquête Démographique et de Santé et à Indicateurs Multiples (EDS-MICS):2011. Yaoundé: ICF International Calverton, Maryland; 2012.
• [10]BUCREP: 3ème Recensement Général de la population et de l’Habitat (3e RGPH): La Population du Cameroun en 2010. Yaoundé: Bureau Central des Recensements et des Etudes de la Population; 2010.
• [11]National AIDS Control Committe- Central Technical Group (NACC-CTG): The Impact of HIV and AIDS in Cameroon through 2020. 2010.
• [12]Ramadhani HO, Thielman NM, Landman KZ, Ndosi EM, Gao F, Kirchherr JL, Shah R, Shao HJ, Morpeth SC, Mcneill JD, Shao JF, Bartlett JA, Crump JA: Predictors of Incomplete Adherence, Virologic Failure, and Antiviral Drug Resistance among HIV-Infected Adults Receiving Antiretroviral Therapy in Tanzania. Clin Infect Dis 2007, 45:1492-1498.
• [13]WHO: Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Micronutrients Indicators: Vitamin and Mineral Nutrition Information System. Geneva: World Health Organization; 2011.
• [14]Tsuchiya N, Pathipvanich P, Yasuda T, Mukoyama Y, Rojanawiwat A, Matsubayashi T, Saeng-aroon S, Auwanit W, Matsuyama A, Sawanpanyalert P, Ariyoshi K, Hospital L: Demographic, Socio-economic, Behavioural and Clinical Factors Predicting Virologic Failure with Generic Fixed-Dose Combination Antiretroviral Therapy before Universal Health Insurance Coverage in Northern Thailand. Southeast Asian J Trop Med Public Health 2009, 40:71-82.
• [15]Shearer WT, Rosenblatt HM, Schluchter MD, Mofenson LM, Denny TN: Immunologic targets of HIV infection: T cells. NICHD IVIG Clinical Trial Group, and the NHLBI P2C2 Pediatric Pulmonary and Cardiac Complications of HIV Infection Study Group. Ann N Y Acad Sci 1993, 693:35-51.
• [16]Cosby CD: Hematologic Disorders Associated with Human Immunodeficiency Virus and AIDS. J Infus Nurs 2007, 30(1):22-32.
• [17]Obirikorang C, Yeboah F: Blood haemoglobin measurement as a predictive indicator for the progression of HIV/AIDS in resource-limited setting. J Biomed Sci 2009, 16:102. BioMed Central Full Text
• [18]Kilaru KR, Kumar A, Sippy N: CD4 cell counts in adults with newly diagnosed HIV infection in Barbados. Pan Am. J. Public Heal. 2004, 16:302-7.
• [19]Richardson BA, Mbori-ngacha D, John-stewart GC, Nduati R, Dana D, Emery S, Kreiss JK, Lavreys L, Panteleeff DD, Overbaugh J: Comparison of Human Immunodeficiency Virus Type 1 Viral Loads in Kenyan Women, Men, and Infants during Primary and Early Infection Comparison of Human Immunodeficiency Virus Type 1 Viral Loads in Kenyan Women, Men, and Infants during Primary and Early. J Virol 2003, 77:7120-7123.
• [20]Wachukwu CK, Abbey SD, Busuri FI, Erhabor O: Changes in Immunohaematological Characteristics of Human Immunodeficiency. J. Med. Lab. Sci. 2007, 13:35348.
• [21]Owiredu WKBA, Quaye L, Amidu NA-MO: Prevalence of anaemia and immunological markers among Ghanaian HAART-naïve HIV-patients and those on HAART. Afr Health Sci 2011, 11:2-15.
• [22]Magadi MA: Understanding the gender disparity in HIV infection across countries in sub-Saharan Africa: evidence from the Demographic and Health Surveys. Sociol. Heal. Illn. 2011, 33:522-539.
• [23]Amornkul PN, Vandenhoudt H, Nasokho P, Odhiambo F, Mwaengo D, Hightower A, Buvé A, Misore A, Vulule J, Vitek C, Glynn J, Greenberg A, Slutsker L, De Cock KM: HIV prevalence and associated risk factors among individuals aged 13–34 years in Rural Western Kenya. PLoS One 2009, 4:e6470.
• [24]Saathoff E, Villamor E, Mugusi F, Bosch RJ, Urassa W, Fawzi WW: Anemia in adults with tuberculosis is associated with HIV and anthropometric status in Dar es Salaam, Tanzania. Int. J. Tuberc. Lung Dis. 2013, 15:925-932.
• [25]Kufa T, Mngomezulu V, Charalambous S, Hanifa Y, Fielding K, Grant AD, Wada N, Chaisson RE, Churchyard GJ, Gounder CR: Undiagnosed tuberculosis among HIV clinic attendees: association with antiretroviral therapy and implications for intensified case finding, isoniazid preventive therapy, and infection control. J Acquir Immune Defic Syndr 2012, 60:e22-8.
• [26]Mata-Marín JA, Gaytán-Martínez JE, Martínez-Martínez RE, Arroyo-Anduiza CI, Fuentes-Allen JL, Casarrubias-Ramirez M: Risk factors and correlates for anemia in HIV treatment-naïve infected patients: a cross-sectional analytical study. BMC Res. Notes 2010, 3:230. BioMed Central Full Text
• [27]Farzadegan H, Hoover DR, Astemborski J, Lyles CM, Margolick JB, Markham RB, Quinn TC, Vlahov D: Early reports Sex differences in HIV-1 viral load and progression to AIDS. Lancet 1998, 352:1510-14.
• [28]Ballesteros-Zebadúa P, Villarreal C, Cocho G, Huerta L, Estrada JL: Differences in HIV-1 viral loads between male and female antiretroviral-untreated mexican patients. Arch Med Res 2013, 4409:3-4.
• [29]Maskew M, At B, Westreich D, Mcnamara L, Ap M, Mp F: Gender differences in mortality and CD4 count response among virally suppressed HIV-positive patients. J. Womens Heal. 2013, 22:1-2.
• [30]Levine A, Berhane K: Prevalence and correlates of anemia in a large cohort of HIV-infected women: Women’s Interagency HIV Study. J Acquir Immune Defic Syndr 2001, 26:28-35.
• [31]Volberding PA, Levine AM, Dieterich D, Mildvan D, Mitsuyasu R, Saag M: Anemia in HIV infection: clinical impact and evidence-based management strategies. Clin Infect Dis 2004, 38:1454-63.
• [32]Mocroft A, Kirk O, Barton SE, Dietrich M, Proenca R, Colebunders R, Pradier C, DArminio Monforte A, Ledergerber B, Lundgren JD: Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. EuroSIDA study group. AIDS 1999, 13:943-50.
• [33]Moore R, Forney D: Anemia in HIV-infected patients receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2002, 29:54-57.
• [34]Semba RD, Shah N, Klein RS, Mayer KH, Schuman P, Vlahov D: Prevalence and cumulative incidence of and risk factors for anemia in a multicenter cohort study of human immunodeficiency virus-infected and -uninfected women. Clin Infect Dis 2002, 34:260-266.
• [35]Patel AK, Pujari S, Patel K, Patel J, Shah N, Patel B, Gupte N: Nevirapine Versus Efavirenz Based Antiretroviral Treatment in Naïve Indian Patients: comparison of comparison of effectiveness in clinical cohort. J Assoc Physicians India 2006, 54:915-918.
• [36]Núñez M, Soriano V, Martín-Carbonero L, Barrios A, Barreiro P, Blanco F, García-Benayas T, González-Lahoz J: SENC (Spanish efavirenz vs. nevirapine comparison) trial: a randomized, open-label study in HIV-infected naive individuals. HIV Clin. Trials 2002, 3:186-94.
• [37]Van den Berg-Wolf M, Hullsiek KH, Peng G, Kozal MJ, Novak RM, Chen L, Crane LR, Macarthur RD: Virologic, immunologic, clinical, safety, and resistance outcomes from a long-term comparison of efavirenz-based versus nevirapine-based antiretroviral regimens as initial therapy in HIV-1-infected persons. HIV Clin Trials 2008, 9:324-36.
• [38]McComsey G, Kitch D, Daar E: Inflammation markers after randomization to abacavir/lamivudine or tenofovir/emtricitabine with efavirenz or atazanavir/ritonavir: ACTG A5224 s, A5202 substudy. AIDS 2012, 26:1371-1385.
• [39]Zoufaly A, An der Heiden M, Kollan C, Bogner JR, Fätkenheuer G, Wasmuth JC, Stoll M, Hamouda O, van Lunzen J: Clinical outcome of HIV-infected patients with discordant virological and immunological response to antiretroviral therapy. J Infect Dis 2011, 203:364-71.
• [40]Arnedo M, Alonso E, Eisenberg N, Ibáñez L, Ferreyra C, Jaén A, Flevaud L, Khamadi S, Roddy P, Gatell JM, Dalmau D: Monitoring HIV viral load in resource limited settings: still a matter of debate? PLoS One 2012, 7:e47391.
• [41]Ferradini L, Jeannin A, Pinoges L, Izopet J, Odhiambo D, Mankhambo L, Karungi G, Szumilin E, Balandine S, Fedida G, Carrieri MP, Spire B, Ford N, Tassie J-M, Guerin PJ, Brasher C: Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment. Lancet 2006, 367:1335-42.
• [42]Bartlett JA, Buda JJ, von Scheele B, Mauskopf JA, Davis EA, Elston R, King MS, Lanier ER: Minimizing resistance consequences after virologic failure on initial combination therapy: a systematic overview. J Acquir Immune Defic Syndr 2006, 41:323-31.
• [43]Sow P, Otieno L, Bissagnene E: Implementation of an antiretroviral access program for HIV-1-infected individuals in resource-limited settings: clinical results from 4 African countries. J Acquir Immune Defic Syndr 2007, 44:262-267.
• [44]Koenig S, Leandre F, Farmer P: Scaling-up HIV treatment programmes in resource-limited settings: the rural Haiti experience. AIDS 2004, 18(supl 3):S21-25.
• [45]Posse M, Meheus F, van Asten H, van der Ven A, Baltussen R: Barriers to access to antiretroviral treatment in developing countries: a review. Trop. Med. Int. Heal. 2008, 13:904-13.
• [46]Charurat M, Oyegunle M, Benjamin R, Habib A, Eze E, Ele P, Ibanga I, Ajayi S, Eng M, Mondal P, Gebi U, Iwu E, Abimiku A, Dakum P, Farley J, Blattner W: Patient retention and adherence to antiretrovirals in a large antiretroviral therapy program in Nigeria: a longitudinal analysis for risk factors. PLoS One 2010, 5:e10584.
• [47]Anude CJ, Eze E, Onyegbutulem HC, Charurat M, Etiebet M-A, Ajayi S, Dakum P, Akinwande O, Beyrer C, Abimiku A, Blattner W: Immuno-virologic outcomes and immuno-virologic discordance among adults alive and on anti-retroviral therapy at 12 months in Nigeria. BMC Infect Dis 2013, 13:113. BioMed Central Full Text
• [48]Glass TR, De Geest S, Weber R, Vernazza PL, Rickenbach M, Furrer H, Bernasconi E, Cavassini M, Hirschel B, Battegay M, Bucher HC: Correlates of self-reported nonadherence to antiretroviral therapy in HIV-infected patients: the Swiss HIV Cohort Study. J Acquir Immune Defic Syndr 2006, 41:385-92.
• [49]Skowron G, Street J, Obee E: Baseline CD4+ cell count, not viral load, correlates with virologic suppression induced by potent antiretroviral therapy. J Acquir Immune Defic Syndr 2001, 28:313-319.
• [50]Bello EJM, Correia AF, Marins JRP, Merchan-Hamann E, Kanzaki LIB: Predictors of virologic failure in HIV/AIDS patients treated with highly active antiretroviral therapy in Brasília, Brazil during 2002–2008. Drug Target Insights 2011, 5:33-41.