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  • 1.
    Carlander, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Karolinska Inst, Dept Med Huddinge, Unit Infect Dis, SE-17177 Stockholm, Sweden.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    van Beirs, Astrid
    Linkoping Univ, Fac Med & Hlth Sci, Linkoping, Sweden.
    Yilmaz, Aylin
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Infect Dis, Gothenburg, Sweden.
    Elfgren, Kristina
    Karolinska Univ Hosp Huddinge, Dept Obstet & Gynaecol, CLINTEC, Stockholm, Sweden.
    Dillner, Joakim
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.
    Sönnerborg, Anders
    Karolinska Inst, Dept Med Huddinge, Unit Infect Dis, SE-17177 Stockholm, Sweden.
    Sparen, Pär
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Suppressive antiretroviral therapy associates with effective treatment of high-grade cervical intraepithelial neoplasia2018In: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 32, no 11, p. 1475-1484Article in journal (Refereed)
    Abstract [en]

    Objectives: To assess if women living with HIV (WLWH) have poorer outcome after treatment of cervical intraepithelial neoplasia grade 2, grade 3, adenocarcinoma in situ or cervical cancer (CIN2+) than HIV-negative women (HNW) and to identify predictors of CIN2+ treatment failure and recurrence in WLWH. Design: Population-based cohort study with follow-up between 1983 and 2015. Methods: The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ (n = 179) sometime between 1983 and 2014. For each WLWH, two HNW resident in the same counties and matched for country of birth, diagnosed with CIN2+, were chosen as controls. Treatment failure was defined as the presence of CIN2+ at initial follow-up. Recurrence was defined as the presence of CIN1+ subsequent to an initial normal follow-up. Results: WLWH were three times more likely to have treatment failure (odds ratio (OR) 3.7 [95% confidence interval (CI) 2.0-6.8]) and five times more likely to recur (hazard ratio 5.0 [95% CI 2.1-11.6]) than HNW. Suppressive antiretroviral therapy (ART) at time of treatment of CIN2+ was associated with reduced OR of treatment failure (OR 0.3 [95% CI 0.1-0.8]). Immunosuppression (CD4(+) cell count < 200 cells/mu l) associated strongly with treatment failure (OR compared with CD4 (+) cell count >= 500: 8.5 [95% CI 2.3-30.7]). Conclusion: Suppressive ART is associated with effective treatment of CIN2+. Early HIV diagnosis and ART are essential for successful CIN2+ treatment.

  • 2.
    Doherty, Tanya
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Chopra, Mickey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Jackson, Debra
    Goga, Ameena
    Colvin, Mark
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Effectiveness of the WHO/UNICEF guidelines on infant feeding for HIV-positive women: results from a prospective cohort study in South Africa2007In: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 21, no 13, p. 1791-1797Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The World Health Organization (WHO) and UNICEF recommend that HIV-positive women should avoid all breastfeeding only if replacement feeding is acceptable, feasible, affordable, sustainable and safe. Little is known about the effectiveness of the implementation of these guidelines in developing country settings. OBJECTIVE: To identify criteria to guide appropriate infant-feeding choices and to assess the effect of inappropriate choices on infant HIV-free survival. METHOD: Prospective cohort study of 635 HIV-positive mother-infant pairs across three sites in South Africa to assess mother to child transmission of HIV. Semistructured questionnaires were used during home visits between the antenatal period and 36 weeks after delivery to collect data concerning appropriateness of infant feeding choices based on the WHO/UNICEF recommendations. RESULTS: Three criteria were found to be associated with improved infant HIV-free survival amongst women choosing to formula feed: piped water; electricity, gas or paraffin for fuel; and disclosing HIV status. Using these criteria as a measure of appropriateness of choice: 95 of 311 women who met the criteria (30.5%) chose to breastfeed and 195 of 289 women who did not meet the criteria (67.4%) chose to formula feed. Infants of women who chose to formula feed without fulfilling these three criteria had the highest risk of HIV transmission/death (hazard ratio, 3.63; 95% confidence interval, 1.48-8.89). CONCLUSIONS: Within operational settings, the WHO/UNICEF guidelines were not being implemented effectively, leading to inappropriate infant-feeding choices and consequent lower infant HIV-free survival. Counselling of mothers should include an assessment of individual and environmental criteria to support appropriate infant-feeding choices.

  • 3. Jackson, Debra J.
    et al.
    Chopra, Mickey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Doherty, Tanya
    Colvin, Mark S.E.
    Levin, Jonathan B.
    Willumsen, Juana F.
    Goga, Ameena E.
    Moodley, Pravi
    Operational effectiveness and 36 week HIV-free survival in the South African programme to prevent mother-to-child transmission of HIV-12007In: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 21, no 4, p. 509-516Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Previous studies on the operational effectiveness of programmes to reduce transmission of HIV from mother-to-child (PMTCT) in Africa have generally been hospital-based pilot studies with short follow-up periods. METHOD: Prospective cohort study to evaluate the routine operational effectiveness of the South African National PMTCT Programme, primarily measured by HIV-free survival at 36 weeks post-delivery. Three of eighteen pilot sites participating in the programme were selected as they reflected differences in circumstances, such as HIV prevalence, socioeconomic status and rural-urban location. A total of 665 HIV-positive mothers and their infants were followed. RESULTS: HIV-free survival at 36 weeks varied significantly across sites with 84% in Paarl, 74% in Umlazi and 65% in Rietvlei (P = 0.0003). Maternal viral load was the single most important factor associated with HIV transmission or death [hazard ratio (HR), 1.54; 95% confidence interval (CI), 1.21-1.95]. Adjusting for health system variables (fewer than four antenatal visits and no antenatal syphilis test) explained the difference between Rietvlei and Paarl (crude HR, 2.27; 95% CI, 1.36-3.77; adjusted HR, 1.81; 95% CI, 0.93-3.50). Exposure to breastmilk feeding explained the difference between Umlazi and Paarl (crude HR, 1.74; 95% CI, 1.06-2.84; adjusted HR, 1.41; 95% CI, 0.81-2.48). CONCLUSION: Ever breastfeeding and underlying inequities in healthcare quality within South Africa are predictors of PMTCT programme performance and will need to be addressed to optimize PMTCT effectiveness.

  • 4. Ranki, A.
    et al.
    Nyberg, M.
    Ovod, V.
    Haltia, Matti
    Elovaara, I.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Haapasalo, H.
    Krohn, K.
    Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia1995In: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 9, no 9, p. 1001-8Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To relate the expression of HIV regulatory proteins and HIV-specific mRNA in the brain cells of infected individuals with clinical neurological disease. DESIGN: Formalin-fixed postmortem brain tissue from 14 HIV-infected adult patients, with previous repeated neurological and neuroradiological examinations, was studied by immunohistochemical and molecular biological methods. Samples from non-infected brains served as controls. METHODS: Immunohistochemistry with monoclonal antibodies (MAb) was combined with in situ RNA hybridization. Target cells were identified with MAb to glial fibrillary acidic protein (GFAP; astrocytes), CD68 (activated macrophages) and Ricinus communis agglutinin (RCA-1; microglia, endothelial cells). For HIV, a panel of MAb against HIV Nef, Tat, Rev and Env proteins or probes specific for all classes of mRNA (nef), for singly or non-spliced mRNA (env) and for non-spliced mRNA (gag/pol) were used. RESULTS: Nef protein was detected in subcortical or subpial astrocytes in seven out of 14 samples, and in multinucleated giant cells in two cases. Gag/pol or env mRNA-expressing astrocytes were detected in four cases. In four out of five cases studied, HIV Rev, but not Tat, was also expressed in astrocytes. Six out of the seven patients with Nef-positive astrocytes had suffered from moderate to severe dementia. The patient with most rapidly progressing severe dementia showed extensive HIV mRNA expression together with Nef and Rev expression in astrocytes. CONCLUSION: In adult human brain, astrocytes are infected by HIV and preferentially express HIV Nef and Rev proteins but are also sometimes productively infected. Astrocyte infection is associated with moderate to severe dementia which agrees with recent knowledge on the housekeeping activities of astrocytes and their eventual role in learning and memory.

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