title: 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.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Muhimbili National Hospital, 65000, Dar es Salaam, Tanzania. mmatty71@gmail.com.|Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. mmatty71@gmail.com.|Public Health Agency of Sweden, Stockholm, Sweden. mmatty71@gmail.com.
authors.forename: Matilda
authors.initials: M
authors.lastname: Ngarina
authors.affiliation: Departments of Obstetrics and Gynecology, Muhimbili University of Health and Allied Sciences, 65001, Dar es Salaam, Tanzania. kilewo1950@gmail.com.
authors.forename: Charles
authors.initials: C
authors.lastname: Kilewo
authors.affiliation: Public Health Agency of Sweden, Stockholm, Sweden. katarinavbg@yahoo.se.
authors.forename: Katarina
authors.initials: K
authors.lastname: Karlsson
authors.affiliation: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, 65001, Dar es Salaam, Tanzania. aboudsaid@yahoo.com.
authors.forename: Said
authors.initials: S
authors.lastname: Aboud
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. annika.karlsson@ki.se.
authors.forename: Annika
authors.initials: A
authors.lastname: Karlsson
authors.affiliation: Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden. Gaetano.Marrone@ki.se.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Marrone
authors.affiliation: Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. gerryleyna@yahoo.com.
authors.forename: Germana
authors.initials: G
authors.lastname: Leyna
authors.affiliation: Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden. anna.mia.ekstrom@ki.se.|Department of Infectious Diseases, Karolinska University Hospital, Huddinge, Stockholm, Sweden. anna.mia.ekstrom@ki.se.
authors.forename: Anna Mia
authors.initials: AM
authors.lastname: Ekström
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. gunnel.biberfeld@ki.se.|Public Health Agency of Sweden, Stockholm, Sweden. gunnel.biberfeld@ki.se.
authors.forename: Gunnel
authors.initials: G
authors.lastname: Biberfeld
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001942:Breast Feeding; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D055118:Medication Adherence; D049590:Postpartum Period; D011247:Pregnancy; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013636:Tanzania; D017211:Treatment Failure; D019562:Viral Load; D014766:Viremia / Q000097:blood*; D055815:Young Adult
chemical_list: D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors