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      HIV viraemia during pregnancy in women receiving preconception antiretroviral therapy in KwaDukuza, KwaZulu-Natal

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      1 , , 2 , 1
      Southern African Journal of HIV Medicine
      AOSIS

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          Abstract

          Background

          Preconception antiretroviral therapy (PCART) followed by sustained viral suppression is effective in preventing mother-to-child transmission of HIV. The rates of persistent and transient viraemia in such patients have not been prospectively assessed in South Africa.

          Objectives

          We determined the prevalence of transient and persistent viraemia in HIV-positive women entering antenatal care on PCART and studied variables associated with viraemia.

          Methods

          We performed a prospective cross-sectional observational study of HIV-positive pregnant women presenting to a primary healthcare facility in KwaZulu-Natal. All had received at least 6 months of first-line PCART. Viral load (VL) was measured, patients were interviewed, adherence estimated using a visual analogue scale and adherence counselling provided. Viral load was repeated after 4 weeks where baseline VL exceeded 50 copies/mL.

          Results

          We enrolled 82 participants. Of them, 59 (72%) pregnancies were unplanned. Fifteen participants (18.3%) were viraemic at presentation with VL > 50 copies/mL. Of these, seven (8.5%) had viral suppression (VL < 50 copies/mL), and eight remained viraemic at the second visit. Adherence correlated significantly with viraemia at baseline. Level of knowledge correlated with adherence but not with lack of viral suppression at baseline. Socio-economic indicators did not correlate with viraemia. No instances of vertical transmission were observed at birth.

          Conclusions

          Approximately 20% of women receiving PCART may demonstrate viraemia. Half of these may be transient. Poor adherence is associated with viraemia, and efforts to encourage and monitor adherence are essential. The rate of unplanned pregnancies is high, and antiretroviral therapy programmes should focus on family planning needs of women in the reproductive age group to prevent viral non-suppression prior to pregnancy.

          Keywords

          Preconception Antiretroviral Therapy; HIV; Viraemia; Antenatal Care; Adherence.

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          Most cited references44

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          Levels of HIV-1 persistence on antiretroviral therapy are not associated with markers of inflammation or activation

          Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but both can persist despite clinically effective ART. The relationships among pre-ART and on-ART levels of HIV-1 and activation are incompletely understood, in part because prior studies have been small or cross-sectional. To address these limitations, we evaluated measures of HIV-1 persistence, inflammation, T cell activation and T cell cycling in a longitudinal cohort of 101 participants who initiated ART and had well-documented sustained suppression of plasma viremia for a median of 7 years. During the first 4 years following ART initiation, HIV-1 DNA declined by 15-fold (93%) whereas cell-associated HIV-1 RNA (CA-RNA) fell 525-fold (>99%). Thereafter, HIV-1 DNA levels continued to decline slowly (5% per year) with a half-life of 13 years. Participants who had higher HIV-1 DNA and CA-RNA before starting treatment had higher levels while on ART, despite suppression of plasma viremia for many years. Markers of inflammation and T cell activation were associated with plasma HIV-1 RNA levels before ART was initiated but there were no consistent associations between these markers and HIV-1 DNA or CA-RNA during long-term ART, suggesting that HIV-1 persistence is not driving or driven by inflammation or activation. Higher levels of inflammation, T cell activation and cycling before ART were associated with higher levels during ART, indicating that immunologic events that occurred well before ART initiation had long-lasting effects despite sustained virologic suppression. These findings should stimulate studies of viral and host factors that affect virologic, inflammatory and immunologic set points prior to ART initiation and should inform the design of strategies to reduce HIV-1 reservoirs and dampen immune activation that persists despite ART.
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            No perinatal HIV-1 transmission from women with effective antiretroviral therapy starting before conception.

            The efficacy of preventing perinatal transmission (PT) of human immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and treatment duration. The objective of this study was to determine whether initiating highly active antiretroviral therapy (ART) before conception has the potential to eliminate PT.
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              Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study

              (2016)
              Summary Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1·50, 95% CI 1·27–1·77 for CD4 cell count <100 cells per μL). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1·48, 95% CI 1·20–1·82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0·626]). Interpretation We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial. Funding The Wellcome Trust.
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                Author and article information

                Journal
                South Afr J HIV Med
                South Afr J HIV Med
                HIVMED
                Southern African Journal of HIV Medicine
                AOSIS
                1608-9693
                2078-6751
                10 April 2019
                2019
                : 20
                : 1
                : 847
                Affiliations
                [1 ]Department of Obstetrics and Gynaecology, School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa
                [2 ]School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa
                Author notes
                Corresponding author: Vuyokazi Ntlantsana, Ntlantsanav@ 123456ukzn.ac.za
                Author information
                http://orcid.org/0000-0002-5882-100X
                http://orcid.org/0000-0003-3580-1513
                http://orcid.org/0000-0002-1520-8635
                Article
                HIVMED-20-847
                10.4102/sajhivmed.v20i1.847
                6494933
                31061722
                792a77fa-5919-45ff-a423-89b3471976e7
                © 2019. The Authors

                Licensee: AOSIS. This work is licensed under the Creative Commons Attribution License.

                History
                : 05 March 2018
                : 05 February 2019
                Categories
                Original Research

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