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      Population uptake and effectiveness of test‐and‐treat antiretroviral therapy guidelines for preventing the global spread of HIV: an ecological cross‐national analysis

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          Abstract

          Objectives

          Although the benefits of adopting test‐and‐treat antiretroviral therapy (ART) guidelines that recommend initiation of ART regardless of CD4 cell counts have been demonstrated at the individual level, there is uncertainty about how this translates to the population level. Here, we explored whether adopting ART guidelines recommending earlier treatment initiation improves population ART access and viral suppression and reduces overall disease transmission.

          Methods

          Data on ART initiation guidelines and treatment coverage, viral suppression, and HIV incidence from 37 European and Central Asian countries were collected from the European Centre for Disease Prevention and Control and the Global HIV Policy Watch and HIV 90‐90‐90 Watch databases. We used multivariate linear regression models to quantify the association of ART initiation guidelines with population ART access, viral suppression, and HIV incidence, adjusting for potential confounding factors.

          Results

          Test‐and‐treat policies were associated with 15.2 percentage points (pp) [95% confidence interval ( CI) 0.8–29.6 pp; P = 0.039] greater treatment coverage (proportion of HIV‐positive people on ART) compared with countries with ART initiation at CD4 cell counts ≤ 350 cells/μL. The presence of test‐and‐treat policies was associated with 15.8 pp (95% CI 2.4–29.1 pp; P = 0.023) higher viral suppression rates (people on ART virally suppressed) compared with countries with treatment initiation at CD4 counts ≤ 350 cells/μL. ART initiation at CD4 counts ≤ 500 cells/μL did not significantly improve ART coverage compared to initiation at CD4 counts ≤ 350 cells/μL but achieved similar degrees of viral suppression as test‐and‐treat.

          Conclusions

          Test‐and‐treat was found to be associated with substantial improvements in population‐level access to ART and viral suppression, further strengthening evidence that rapid initiation of treatment will help curb the spread of HIV.

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          Most cited references30

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          Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

          An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.
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            Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial.

            The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries. We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life. From November, 1997, to April, 1999, we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala, Uganda. We randomly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth, or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily to babies for 7 days after birth. We tested babies for HIV-1 infection at birth, 6-8 weeks, and 14-16 weeks by HIV-1 RNA PCR. We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis. Nearly all babies (98.8%) were breastfed, and 95.6% were still breastfeeding at age 14-16 weeks. The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were: 10.4% and 8.2% at birth (p=0.354); 21.3% and 11.9% by age 6-8 weeks (p=0.0027); and 25.1% and 13.1% by age 14-16 weeks (p=0.0006). The efficacy of nevirapine compared with zidovudine was 47% (95% CI 20-64) up to age 14-16 weeks. The two regimens were well tolerated and adverse events were similar in the two groups. Nevirapine lowered the risk of HIV-1 transmission during the first 14-16 weeks of life by nearly 50% in a breastfeeding population. This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries.
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              Systematic Review of HIV Transmission between Heterosexual Serodiscordant Couples where the HIV-Positive Partner Is Fully Suppressed on Antiretroviral Therapy

              Background The risk of sexual HIV transmission in serodiscordant couples when the HIV-positive partner has full virologic suppression on combination antiretroviral therapy (cART) is debated. This study aims to systematically review observational studies and randomized controlled trials (RCTs), evaluating rates of sexual HIV transmission between heterosexual serodiscordant couples when the HIV-positive partner has full suppression on cART. Methods and Findings We searched major bibliographic databases to November 2012 for relevant observational studies and RCTs without language restrictions. Conference proceedings, key journals and bibliographies were also searched. Studies reporting HIV transmission rates, cART histories and viral loads of the HIV-positive partners were included. Two reviewers extracted methodologic characteristics and outcomes. Of 20,252 citations, 3 studies met all eligibility criteria with confirmed full virologic suppression in the HIV-positive partner. We included 3 additional studies (2 cohort studies, 1 RCT) that did not confirm viral suppression in the HIV-positive partner at transmission in a secondary meta-analysis. Methodologic quality was reasonable. The rate of transmission in the 3 studies confirming virologic suppression was 0 per 100 person-years (95% CI = 0–0.05), with low heterogeneity (I2 = 0%). When we included the 3 studies that did not confirm virologic suppression, the rate of transmission was 0.14 per 100 person-years (95%CI = 0.04–0.31) (I2 = 0%). In a sensitivity analysis including all 6 studies, the rate of transmission was 0 per 100 person-years (95%CI = 0–0.01) after omitting all transmissions with known detectable or unconfirmed viral loads, as full suppression in these cases was unlikely. Limitations included lack of data on same-sex couples, type of sexual intercourse (vaginal vs. anal), direction of HIV transmission, exact viral load at the time of transmission, sexually transmitted infections (STI) rates, and extent of condom use. Conclusions Our findings suggest minimal risk of sexual HIV transmission for heterosexual serodiscordant couples when the HIV-positive partner has full viral suppression on cART with caveats regarding information on sexual intercourse type, STIs, and condom use. These findings have implications when counseling heterosexual serodiscordant couples on sexual and reproductive health. More research is needed to explore HIV transmission risk between same-sex couples.
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                Author and article information

                Contributors
                ana.mdzlopez@gmail.com
                Journal
                HIV Med
                HIV Med
                10.1111/(ISSN)1468-1293
                HIV
                HIV Medicine
                John Wiley and Sons Inc. (Hoboken )
                1464-2662
                1468-1293
                29 May 2019
                September 2019
                : 20
                : 8 ( doiID: 10.1111/hiv.v20.8 )
                : 501-512
                Affiliations
                [ 1 ] Green Templeton College University of Oxford Oxford UK
                [ 2 ] Department of Public Health & Policy London School of Hygiene & Tropical Medicine London UK
                [ 3 ] Dondena Research Centre University of Bocconi Milan Italy
                [ 4 ] Independent Public Health Consultant San Francisco CA USA
                [ 5 ] Independent Public Health Consultant Delhi India
                [ 6 ] European Centre for Disease Prevention and Control Stockholm Sweden
                Author notes
                [*] [* ]Correspondence: Ms A. Mendez‐Lopez, Green Templeton College, 43 Woodstock Road, Oxford OX2 6HG, UK. Tel/fax: +441865274770; e‐mail: ana.mdzlopez@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-8831-1684
                https://orcid.org/0000-0002-0121-9683
                Article
                HIV12750
                10.1111/hiv.12750
                6772052
                31140715
                6b80d127-a1bb-4a3d-9c1b-0b26ec4c2c9b
                © 2019 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 March 2019
                Page count
                Figures: 4, Tables: 3, Pages: 12, Words: 7549
                Funding
                Funded by: European Centre for Disease Prevention and Control
                Funded by: Wellcome Trust Investigator Award
                Award ID: CYRYTR00
                Funded by: European Research Council
                Award ID: HRES313590
                Funded by: La Caixa Foundation
                Award ID: LCF/BQ/EU16/11560036
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                hiv12750
                September 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.9 mode:remove_FC converted:01.10.2019

                Infectious disease & Microbiology
                ecological,health systems,hiv care continuum,structural drivers,test‐and‐treat

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