期刊论文详细信息
BMC Infectious Diseases
Virologic and immunologic failure, drug resistance and mortality during the first 24 months postpartum among HIV-infected women initiated on antiretroviral therapy for life in the Mitra plus Study, Dar es Salaam, Tanzania
Gunnel Biberfeld4  Anna Mia Ekström1  Germana Leyna2  Gaetano Marrone7  Annika Karlsson3  Said Aboud6  Katarina Karlsson4  Charles Kilewo5  Matilda Ngarina4 
[1] Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Huddinge, Sweden;Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden;Public Health Agency of Sweden, Stockholm, Sweden;Departments of Obstetrics and Gynecology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden
关键词: Option B+;    Tanzania;    Drug resistance;    Antiretroviral therapy;    Prevention of mother-to-child transmission;    Virologic failure;    HIV;   
Others  :  1172078
DOI  :  10.1186/s12879-015-0914-z
 received in 2014-09-21, accepted in 2015-03-25,  发布年份 2015
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【 摘 要 】

Background

In the Mitra plus study of prevention of mother-to-child transmission of HIV-1, which included 501 women in Dar es Salaam, Tanzania, triple antiretroviral therapy (ART) was given from late pregnancy throughout breastfeeding up to 6 months postnatally. Here we report findings in a sub-cohort of women with ≤200 CD4cells/μL at enrolment who were continued on ART for life and followed up during 24 months after delivery to determine virologic and immunologic responses, drug resistance and mortality.

Methods

Blood samples for viral load and CD4 counts testing were collected at enrolment and at 3, 6, 12 and 24 months postpartum. HIV drug resistance testing was performed at 12 months. Data analysis included descriptive statistics and multivariate analysis using Generalized Estimated Equations of 73 women with at least two postpartum assessments. The mortality analysis included 84 women who had delivered.

Results

The proportion of women with a viral load ≥400 copies/mL was 97% (71/73) at enrolment, 16% (11/67), 22% (15/69), 61% (36/59) and 86% (48/56) at 3, 6, 12 and 24 months postpartum, respectively. The proportion of women with immunologic failure was 12% (8/69), 25% (15/60) and 41% (24/58) at 6, 12 and 24 months, respectively. At 12 months, drug resistance was demonstrated in 34% (20/59), including 12 with dual-class resistance. Self-report on drug adherence was 95% (64/68), 85% (56/66), 74% (39/53) and 65% (30/46) at 3, 6, 12 and 24 months, respectively. The mortality rate was 5.9% (95% CI 2.5-13.7%) at 24 months. The probability of virologic and immunologic failure was significantly higher among women who reported non-perfect adherence to ART at month 24 postpartum.

Conclusions

Following an initial decline of viral load, virologic failure was common at 12 and 24 months postpartum among women initiated on ART for life during pregnancy because of low CD4 cell counts. A high proportion of viremic mothers also had resistance mutations. However, at 24 months follow-up, the mortality rate was still fairly low. Continuous adherence counseling and affordable means of monitoring of the virologic response are crucial for successful implementation of the WHO Option B+ guidelines to start all HIV-infected pregnant women on ART for life.

【 授权许可】

   
2015 Ngarina et al.; licensee BioMed Central.

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【 参考文献 】
  • [1]UNAIDS Regional Fact Sheet 2012; Sub-saharan Africa. Available at http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/2012_FS_regional_ssa_en.pdf accessed date: October 2012.
  • [2]UNAIDS report on the global AIDS epidemic, 2013. Available at http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdf accessed date:March 2013.
  • [3]UNAIDS Progress report on the Global PlanAvailable at http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2013/20130625_progress_global_plan_en.pdf accessed date: May 2012.
  • [4]Tanzania 2011–12 HIV/AIDS and malaria indicator survey. Accessed at http://www.measuredhs.com/pubs/pdf/SR196/SR196.pdf.
  • [5]Country progress reporting. Tanzania Mainland, March 30, 2012. Available at http://www.unaids.org/en/dataanalysis/monitoringcountryprogress/progressreports/2012countries/ce_TZ_Narrative_Report[1].pdf accessed May 2012.
  • [6]Tanzania Demographic and Health Survey 2010. Available at http://www.measuredhs.com/pubs/pdf/FR243/FR243%5B24June2011%5D.pdf accessed December 2012.
  • [7]Kilewo C, Karlsson K, Massawe A, Lyamuya E, Swai A, Mhalu F, et al.: Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the Mitra study. J Acquir Immune Defic Syndr 2008, 48(3):315-23.
  • [8]Kilewo C, Karlsson K, Ngarina M, Massawe A, Lyamuya E, Swai A, et al.: Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating mothers with triple antiretroviral therapy in Dar es Salaam, Tanzania: the Mitra plus study. J Acquir Immune Defic Syndr 2009, 52:406-16.
  • [9]Thomas KT, Masaba R, Borkowf CB, Ndivo R, Zeh C, Misore A, et al.: Triple- antiretroviral prophylaxis to prevent mother to child transmission through breastfeeding – Kisumu breastfeeding study, Kenya: a clinical trial. PLoS Med 2011, 8(3):e1001015.
  • [10]Shapiro RL, Hughes MD, Ogwu A, Kitch D, Lockman S, Moffat C, et al.: Antiretroviral regimens in pregnancy and breast-feeding in Botswana. N Engl J Med 2010, 362(24):2282-94.
  • [11]The Kesho Bora Study Group: Triple antiretroviral compared with single-dose Nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child-transmission of HIV-1(Kesho Bora Study): a randomized controlled trial Lancet Infect Dis 2011, 11:171-80.
  • [12]Kumwenda NI, Hoover DR, Mofenson LM, Thigpen MC, Kafulafula G, Li Q, et al.: Extended antiretroviral prophylaxis toreduce breast-milk HIV-1 transmission. N Eng J Med 2008, 359:119-29.
  • [13]Study Team SWEN, Bedri A, Gudetta B, Isehak A, Kumbi S, Lulseged S, et al.: Extended-dose nevirapine to 6 weeks of age of infant to prevent HIV transmission via breastfeeding in Ethiopia, India and Uganda: an analysis of the three randomised controlled trials. Lancet 2008, 372:300-13.
  • [14]Chasela CS, Hudgens MG, Jamieson DJ, Kayira D, Hosseinipour MC, Kourtis AP, et al.: Maternal or infant antiretroviral drugs to reduce HIV-1 transmission. N Engl J Med 2010, 362:2271-81.
  • [15]Taha TE, Li Q, Hoover DR, Mipando L, Nkanaunena K, Thigpen MC, et al.: Post-exposure prophylaxis of breastfeeding HIV- exposed infants with antiretroviral drugs to age 14 weeks:updated efficacy results of the PEPI-Malawi trial. J Acquir Immune Defic Syndr 2011, 57(4):319-25.
  • [16]Jamieson DJ, Chasela CS, Hudgens MG, King CC, Kourtis AP, Kayira D, et al.: Maternal and infant antiretroviral regimens to prevent postnatal HIV-1 transmission: 48-week follow-up of the BAN randomized controlled trial. Lancet 2012, 379:2449-58.
  • [17]Coovadia HM, Brown ER, Fowler MG, Chipato T, Moodley D, Manji K, et al.: Efficacy and safety of an extended Nevirapine regimen in infant children of breast-feeding mothers with HIV-1infectionfor prevention of postnatal HIV-1 transmission (HPTN 046): a randomized, double blind, placebo-controlled trial. Lancet 2012, 379:221-8.
  • [18]WHO, HIV/AIDS Programme. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants; Recommendations for a public health approach WHO 2010. Available at http://whqlibdoc.who.int/publications/2010/9789241599818_eng.pdf.
  • [19]Siegfried NL, Uthman OA, Rutherford GW: Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults (Review). Cochrane Lib 2011. 2010, 17(3):CD008272. doi:10.1002/14651858.CD008272.pub2
  • [20]Severe P, Juste MAC, Ambroise A, Eliacin L, Marchand C, Apollon S, et al.: Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N Engl J Med 2010, 363(3):257-65.
  • [21]Antiretroviral drugs for treating pregnant women and preventing HIV infection in infantsGuidelines on care, treatment and support for women living with HIV/AIDS and their children in resource-constrained settings. June 2004. Available at http://www.who.int/hiv/pub/mtct/guidelinesarv/en/Accessed December 2012.
  • [22]WHO (2013). Consolidated ARV guidelines. Accessed at http://www.who.int/hiv/pub/guidelines/arv2013/intro/rag/en/index4.html.
  • [23]Barth RE, van der Loeff MF S, Schuurman R, Hoepelman AL, Wensing AM: Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. Lancet Infect Dis 2010, 10:155-66.
  • [24]Stadeli KM, Richman DD: Rates of emergence of HIV drug resistance in resource-limited settings: a systematic review. Antivir Ther 2013, 18(1):115-23. Doi:10.3851/IMP2437
  • [25]The Petra study team: Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda [Petra study]: a randomized, double-blind, placebo-controlled trial Lancet 2002, 359:1178-86.
  • [26]Karnofsky’s score: can be downloaded from the website below.http://www.rand.org/health/surveys_tools/mos/mos_core_36item_survey.html#.UEhzh8Plf94.mailto.
  • [27]Urassa WK, Mbena EM, Swai AB, Gaines H, Mhalu FS, Biberfeld G: Lymphocyte subset enumeration in HIV sero-negative and HIV-1 sero-positive adults in Dar es Salaam, Tanzania: determination of reference values in males and females and comparison of two flow cytometric methods. J Immunol Methods 2003, 277:65-74.
  • [28]World Health Organization. Antiretroviral therapy for HIV infection in adult and adolescents in resource-limited settings: towards universal access. Recommendations for a public health approach; 2006: page 34–38. Available at:http://www.who.int/hiv/pub/guidelines/adult/en/.
  • [29]Murillo W, de Rivera IL, Parham L, Jovel E, Palou E, Karlsson AC, et al.: Prevalence of drug resistance and importance of viral load measurement in Honduran HIV-infected patients failing antiretroviral treatment. HIV Med 2010, 11(2):95-103.
  • [30]Lindstrom A, Albert J: A simple and sensitive ‘in-house’ method for determining genotypic drug resistance in HIV-1. J Virol Methods 2003, 107:45-51.
  • [31]Kilewo C, Karlsson K, Swai A, Massawe A, Lyamuya E, Mhalu F, et al.: Mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load in a cohort of breast-feeding HIV-1infected women in Dar es Salaam. Tanzania J Acquir Immune Defic Syndr 2005, 38(5):598-602.
  • [32]Ngarina M, Popenoe R, Kilewo C, Biberfeld G, Ekström AM: Reasons for poor adherence to antiretroviral therapy postnatally in HIV-1 infected women treated for their own health:experiences from the Mitra Plus study in Tanzania. BMC Public Health 2013, 13:450. Doi:10.1186/1471-2458-13-450 BioMed Central Full Text
  • [33]Ferguson L, Lewis J, Grants AD, Watson-Jones D, Vusha S, Ong’ech JO, et al.: Patient attrition between diagnosis with HIV in pregnancy-related services and long-term HIV care and treatment services in Kenya: a retrospective study. J Acquir Immune Defic Syndr 2012, 60(3):e90-7.
  • [34]Ferguson L, Grants AD, Watson-Jones D, Kahawita T, Ong’ech JO, Ross DA: Linking women who test HIV-positive in pregnancy related services to long-term HIV care and treatment services: a systematic review. Trop Med Int Health 2012, 17(5):564-80.
  • [35]Kalembo WF, Zgambo M. Loss to follow-up: A major challenge to successful implementation of prevention of mother-to-child transmission of HIV-1 programs in sub-Saharan Africa. ISRN AIDS, 2012: 589817 doi:10.5402/2012/589817.
  • [36]Nachega JB, Uthman OA, Anderson J, Peltzer K, Wampold S, Cotton MF, et al.: Adherence to antiretroviral therapy during and after pregnancy in low-income, middle-income, and high-income countries: a systematic review and meta-analysis. AIDS 2012, 26(16):2039-52.
  • [37]Kaplan R, Orrell C, Zwane E, Bekker LG, Wood R: Loss to follow-up and mortality among pregnant women referred to a community clinic for antiretroviral treatment. AIDS 2008, 22(13):1679-81.
  • [38]Toro PL, Katyal M, Carter RJ, Myer L, El-Sadr WM, Nash D, et al.: Initiation of antiretroviral therapy among pregnant women in resource-limited countries: CD4+ cell count response and program retention. AIDS 2010, 24:515-24.
  • [39]Anude CJ, Eze E, Onyegbutulem HC, Charurat M, Etiebet MA, Ajayi S, et al.: 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
  • [40]Rawizza HE, Chaplin B, Meloni ST, Eisen G, Rao T, Sankale JL, et al.: Immunologic criteria are poor predictors of virologic outcome: Implications of HIV treatment monitoring in resource-limited settings. Clin Infect Dis 2011, 53(12):1283-90.
  • [41]Reynolds SJ, Nakigoza G, Newell K, Ndyanabo A, Galiwongo R, Boaz I, et al.: Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda. AIDS 2009, 23(6):697-700.
  • [42]Moore DM, Awor A, Downing R, Kaplan J, Montaner JS, Hancock J, et al.: CD4+ T-cell count monitoring does not accurately identify HIV-infected adults with virologic failure receiving antiretroviral therapy. J Acquir Immune Defic Syndr 2008, 49(5):477-84.
  • [43]Badri M, Lawn SD, Wood R: Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting. BMC Infect Dis 2008, 8:89. BioMed Central Full Text
  • [44]Coffie PA, Ekouevi DK, Chaix ML, Tonwe-Gold B, Clarisse AB, Becquet R, et al.: Maternal 12-month response to antiretroviral therapy following prevention of mother-to-child transmission of HIV type 1, Ivory Coast. 2003–2006. Clin Infect Dis 2008, 46(4):611-21.
  • [45]Datay MI, Boulle A, Mant D, Yudkin P: Associations with virologic treatment failure in adults on antiretroviral therapy in South Africa. J Acquir Immune Defic Syndr 2010, 54(5):489-95.
  • [46]El-Khatib Z, Katzenstein D, Marrone G, Laher F, Mohapi L, Petzold M, et al.: Adherence to drug re-fill is a useful early warning indicator of virologic and immunologic failure among HIV patients on first-line ART in South Africa. PLoS One 2011, 6(3):e17518.
  • [47]El-Khatib Z, Ekstrom AM, Coovadia A, Abrams EJ, Petzold M, Katzenstein D, et al.: Adherence and virologic suppression during first 24 weeks on antiretroviral therapy among women in Johannesburg, South Africa – a prospective cohort study. BMC Public Health 2011, 11:88. doi:10.1186/1471-2458-11-88 BioMed Central Full Text
  • [48]Vairo F, Nicastri E, Liuzzi G, Chaula Z, Nguhuni B, Bevilacqua N, et al.: HIV-1 drug resistance in recently HIV-infected pregnant mother’s naïve to antiretroviral therapy in Dodoma urban, Tanzania.”. BMC Infect Dis 2013, 13:439. BioMed Central Full Text
  • [49]Mosha F, Urassa W, Aboud S, Lyamuya E, Sandstrom E, Bredell H, et al.: Prevalence of genotypic resistance to antiretroviral drugs in treatment-naive youths infected with diverse HIV type 1 subtypes and recombinant forms in Dar es Salaam. Tanzania AIDS Res Hum Retroviruses 2011, 27(4):377-82.
  • [50]Zeh C, Weidle PJ, Nafisa L, Lwamba HM, Okonji J, Anyango E, et al.: HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. PLoS Med 2011, 8(3):e1000430. Doi:10.1371/journal.pmed.1000430
  • [51]Fogel J, Li Q, Taha TE, Hoover DR, Kumwenda NI, Mofenson LM, et al.: Initiation of antiretroviral treatment in women after delivery can induce multiclass drug resistance in breastfeeding HIV-infected infants. Clin Infect Dis 2011, 52(8):1069-76.
  • [52]Burda ST, Viswanath R, Zhao J, Kinge T, Anyangwe C, Tinyami ET, et al.: Reverse transcriptase drug-resistance mutations in chronically infected individuals receiving or naive to HAART in Cameroon. J Med Virol 2010, 82(2):187-96.
  • [53]Dagnra AY, Vidal N, Mensah A, Patassi A, Aho K, Salou M, 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. BioMed Central Full Text
  • [54]Hamers RL, Sigaloff KCE, Wensing AM, Wallis CL, Kityo C, Siwale M, et al.: Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies. Clin Infec Dis 2012, 54(11):1660-9.
  • [55]Bertagnolio S, Perno CF, Vella S, Pillay D: The impact of HIV drug resistance on the selection of first- and second – line ART in resource limited settings. J Infect Dis 2013, 207(suppl 2):S45-8.
  • [56]Tenthani L, Haas AD, Tweya H, Jahn A, van Oosterhout JJ, Chimbwandira F, et al.: Retention in care under universal antiretroviral therapy for HIV-infected pregnant and breastfeeding women (‘Option B+’) in Malawi. AIDS 2014, 28:589-98.
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