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Theuring S.,Charite - Medical University of Berlin | Sewangi J.,Regional AIDS Control Program Mbeya Region | Nchimbi P.,PMTCT Services Mbeya Region | Harms G.,Charite - Medical University of Berlin | Mbezi P.,PMTCT Services Mbeya Region
AIDS Care - Psychological and Socio-Medical Aspects of AIDS/HIV | Year: 2014

Providing full antiretroviral therapy (ART) to all HIV-positive, pregnant women with treatment indication could significantly reduce overall mother-to-child transmission. However, the effectiveness of referring HIV-positive antenatal care (ANC) clients with a treatment indication to ART services has rarely been assessed to date. We retrospectively followed-up data of a cohort of treatment-eligible ANC clients in Mbeya Region, Tanzania by retracing and merging registries of ANC, Care and Treatment Centers (CTC), and Infant Care. ART initiation and ART duration before delivery served as primary outcome indicators to assess referral effectiveness. We retraced data of 60 ANC clients with treatment indication: 39 (65%) started predelivery ART and 21 (35%) remained untreated during pregnancy. Eight (13.3%) did not initiate ART at all within the observation period. Women starting ART before delivery had significantly lower CD4-cell counts at enrollment than nonstarters (medians: 207.5 vs. 292 cells/μl; p = 0.013). Predelivery ART starters had experienced a significantly shorter duration between staff-declared "ART readiness" and actual ART start (medians: 0 vs. 28 days; p = 0.0004). The median ART duration prior to delivery was 57 days; only eight women (13.3%) accomplished ≥90 days ART intake during pregnancy. Early enrollment in ANC at ≤24 gestational weeks was associated with longer duration of predelivery ART. At maternity wards, 24.3% of treatment-eligible mothers and newborns with retraceable delivery data had received no or inadequate antiretrovirals. Within 6 months postdelivery, women attended on average 3.5 out of 6 requested CTC visits. Concluding, every third treatment-eligible woman in this cohort was not covered through ART before delivery, and predelivery ART duration was mostly suboptimal regarding vertical transmission prevention. HIV-positive women need to be encouraged to approach ANC early in pregnancy, and health services need to address unnecessary time gaps before ART initiation. In addition, inclusive ART services for HIV-positive ANC clients should be seriously discussed. © 2013 Taylor & Francis.


Kirsten I.,Charite - Medical University of Berlin | Sewangi J.,Regional AIDS Control Program Mbeya Region | Kunz A.,Charite - Medical University of Berlin | Dugange F.,Kyela District Hospital | And 4 more authors.
PLoS ONE | Year: 2011

Background: Since 2008, Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend combination regimen for mother and infant starting in gestational week 28. Combination prophylaxis is assumed to be more effective and less prone to resistance formation compared to single-drug interventions, but the required continuous collection and intake of drugs might pose a challenge on adherence especially in peripheral resource-limited settings. This study aimed at analyzing adherence to combination prophylaxis under field conditions in a rural health facility in Kyela, Tanzania. Methods and Findings: A cohort of 122 pregnant women willing to start combination prophylaxis in Kyela District Hospital was enrolled in an observational study. Risk factors for decline of prophylaxis were determined, and adherence levels before, during and after delivery were calculated. In multivariate analysis, identified risk factors for declining pre-delivery prophylaxis included maternal age below 24 years, no income-generating activity, and enrolment before 24.5 gestational weeks, with odds ratios of 5.8 (P = 0.002), 4.4 (P = 0.015) and 7.8 (P = 0.001), respectively. Women who stated to have disclosed their HIV status were significantly more adherent in the pre-delivery period than women who did not (P = 0.004). In the intra- and postpartum period, rather low drug adherence rates during hospitalization indicated unsatisfactory staff performance. Only ten mother-child pairs were at least 80% adherent during all intervention phases; one single mother-child pair met a 95% adherence threshold. Conclusions: Achieving adherence to combination prophylaxis has shown to be challenging in this rural study setting. Our findings underline the need for additional supervision for PMTCT staff as well as for clients, especially by encouraging them to seek social support through status disclosure. Prophylaxis uptake might be improved by preponing drug intake to an earlier gestational age. Limited structural conditions of a healthcare setting should be taken into serious account when implementing PMTCT combination prophylaxis. © 2011 Kirsten et al.


Hauser A.,Robert Koch Institute | Kuecherer C.,Robert Koch Institute | Kunz A.,Charite - Medical University of Berlin | Dabrowski P.W.,Robert Koch Institute | And 9 more authors.
PLoS ONE | Year: 2015

Background Pregnant HIV-infected women were screened for the development of HIV-1 drug resistance after implementation of a triple-antiretroviral transmission prophylaxis as recommended by the WHO in 2006. The study offered the opportunity to compare amplicon-based 454 ultradeep sequencing (UDS) and allele-specific real-time PCR (ASPCR) for the detection of drug-resistant minor variants in the HIV-1 reverse transcriptase (RT). Methods Plasma samples from 34 Tanzanian women were previously analysed by ASPCR for key resistance mutations in the viral RT selected by AZT, 3TC, and NVP (K70R, K103N, Y181C, M184V, T215Y/F). In this study, the RT region of the same samples was investigated by amplicon-based UDS for resistance mutations using the 454 GS FLX System. Results Drug-resistant HIV-variants were identified in 69% (20/29) of women by UDS and in 45% (13/29) by ASPCR. The absolute number of resistance mutations identified by UDS was twice that identified by ASPCR (45 vs 24). By UDS 14 of 24 ASPCR-detected resistance mutations were identified at the same position. The overall concordance between UDS and ASPCR was 61.0% (25/41). The proportions of variants quantified by UDS were approximately 2-3 times lower than by ASPCR. Amplicon generation from samples with viral loads below 20,000 copies/ml failed more frequently by UDS compared to ASPCR (limit of detection = 650 copies/ml), resulting in missing or insufficient sequence coverage. Conclusions Both methods can provide useful information about drug-resistant minor HIV-1 variants. ASPCR has a higher sensitivity than UDS, but is restricted to single resistance mutations. In contrast, UDS is limited by its requirement for high viral loads to achieve sufficient sequence coverage, but the sequence information reveals the complete resistance patterns within the genomic region analysed. Improvements to the UDS limit of detection are in progress, and UDS could then facilitate monitoring of drug-resistant minor variants in the HIV-1 quasispecies. © 2015 Hauser et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original author and source are credited.


Kunz A.,Charite - Medical University of Berlin | von Wurmb-Schwark N.,University of Kiel | Sewangi J.,Regional AIDS Control Program Mbeya Region | Ziske J.,Charite - Medical University of Berlin | And 8 more authors.
PLoS ONE | Year: 2012

Background: Zidovudine (AZT) constitutes part of the recommended regimens for prevention and treatment of HIV-1 infection. At the same time, AZT as well as HIV-1 infection itself may induce mitochondrial damage. In this study, we analyzed the impact of prenatal AZT-exposure on mitochondrial alterations in HIV-infected women and their infants. Methods: Mitochondrial DNA (mtDNA) levels in placentas of HIV-1 infected Tanzanian women with and without prenatal AZT exposure, and in the umbilical cords of their AZT-exposed/unexposed infants were quantified using real-time PCR. Furthermore, we checked for the most common mitochondrial deletion in humans, the 4977 base pair deletion (dmtDNA4977) as a marker for mitochondrial stress. Results: 83 women fulfilled the inclusion criteria. 30 women had been treated with AZT (median duration 56 days; IQR 43-70 days) while 53 women had not taken AZT during pregnancy. Baseline maternal characteristics in the two groups were similar. The median mtDNA levels in placentas and umbilical cords of women (311 copies/cell) and infants (190 copies/cell) exposed to AZT were significantly higher than in AZT-unexposed women (187 copies/cell; p = 0.021) and infants (127 copies/cell; p = 0.037). The dmtDNA4977 was found in placentas of one woman of each group and in 3 umbilical cords of AZT-unexposed infants but not in umbilical cords of AZT-exposed infants. Conclusions: Antenatal AZT intake did not increase the risk for the common mitochondrial deletion dmtDNA4977. Our data suggests that AZT exposure elevates mtDNA levels in placentas and umbilical cords possibly by positively influencing the course of maternal HIV-1 infection.


Ziske J.,Charite - Medical University of Berlin | Kunz A.,Charite - Medical University of Berlin | Sewangi J.,Regional AIDS Control Program Mbeya Region | Lau I.,Charite - Medical University of Berlin | And 5 more authors.
PLoS ONE | Year: 2013

Introduction: Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend an antiretroviral combination regimen involving zidovudine (AZT) during pregnancy, single-dosed nevirapine at labor onset, AZT plus Lamivudine (3TC) during delivery, and AZT/3TC for 1-4 weeks postpartum. As drug toxicities are a relevant concern, we assessed hematological alterations in AZT-exposed women and their infants. Methods and Materials: A cohort of HIV-positive women, either with AZT intake (n = 82, group 1) or without AZT intake (n = 62, group 2) for PMTCT during pregnancy, was established at Kyela District Hospital, Tanzania. The cohort also included the infants of group 1 with an in-utero AZT exposure ≥4 weeks, receiving AZT for 1 week postpartum (n = 41), and infants of group 2 without in-utero AZT exposure, receiving a prolonged 4-week AZT tail (n = 58). Complete blood counts were evaluated during pregnancy, birth, weeks 4-6 and 12. Results: For women of group 1 with antenatal AZT intake, we found a statistically significant decrease in hemoglobin level, red blood cells, white blood cells, granulocytes, as well as an increase in red cell distribution width and platelet count. At delivery, the median red blood cell count was significantly lower and the median platelet count was significantly higher in women of group 1 compared to group 2. At birth, infants from group 1 showed a lower median hemoglobin level and granulocyte count and a higher frequency of anemia and granulocytopenia. At 4-6 weeks postpartum, the mean neutrophil granulocyte count was significantly lower and neutropenia was significantly more frequent in infants of group 2. Conclusions: AZT exposure during pregnancy as well as after birth resulted in significant hematological alterations for women and their newborns, although these changes were mostly mild and transient in nature. Research involving larger cohorts is needed to further analyze the impact of AZT-containing regimens on maternal and infant health. © 2013 Ziske et al.

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