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      A decade of sustained geographic spread of HIV infections among women in Durban, South Africa

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          Abstract

          Background

          Fine scale geospatial analysis of HIV infection patterns can be used to facilitate geographically targeted interventions. Our objective was to use the geospatial technology to map age and time standardized HIV incidence rates over a period of 10 years to identify communities at high risk of HIV in the greater Durban area.

          Methods

          HIV incidence rates from 7557 South African women enrolled in five community-based HIV prevention trials (2002–2012) were mapped using participant household global positioning system (GPS) coordinates. Age and period standardized HIV incidence rates were calculated for 43 recruitment clusters across greater Durban. Bayesian conditional autoregressive areal spatial regression (CAR) was used to identify significant patterns and clustering of new HIV infections in recruitment communities.

          Results

          The total person-time in the cohort was 9093.93 years and 613 seroconversions were observed. The overall crude HIV incidence rate across all communities was 6·74 per 100PY (95% CI: 6·22–7·30). 95% of the clusters had HIV incidence rates greater than 3 per 100PY. The CAR analysis identified six communities with significantly high HIV incidence. Estimated relative risks for these clusters ranged from 1.34 to 1.70. Consistent with these results, age standardized HIV incidence rates were also highest in these clusters and estimated to be 10 or more per 100 PY.

          Compared to women 35+ years old younger women were more likely to reside in the highest incidence areas (aOR: 1·51, 95% CI: 1·06–2·15; aOR: 1.59, 95% CI: 1·19–2·14 and aOR: 1·62, 95% CI: 1·2–2·18 for < 20, 20–24, 25–29 years old respectively). Partnership factors (2+ sex partners and being unmarried/not cohabiting) were also more common in the highest incidence clusters (aOR 1.48, 95% CI: 1.25–1.75 and aOR 1.54, 95% CI: 1.28–1.84 respectively).

          Conclusion

          Fine geospatial analysis showed a continuous, unrelenting, hyper HIV epidemic in most of the greater Durban region with six communities characterised by particularly high levels of HIV incidence. The results motivate for comprehensive community-based HIV prevention approaches including expanded access to PrEP. In addition, a higher concentration of HIV related services is required in the highest risk communities to effectively reach the most vulnerable populations.

          Electronic supplementary material

          The online version of this article (10.1186/s12879-019-4080-6) contains supplementary material, which is available to authorized users.

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          Most cited references50

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          Inference from Iterative Simulation Using Multiple Sequences

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            Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.

            Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03). Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).
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              Tenofovir-based preexposure prophylaxis for HIV infection among African women.

              Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events. None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.).
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                Author and article information

                Contributors
                +27 31 2423635 , Gita.Ramjee@mrc.ac.za
                sartorius@ukzn.ac.za
                nmorris@mrc.ac.za
                Hwand@kirby.unsw.edu.au
                Tarylee.Reddy@mrc.ac.za
                Justin.Yssel@mrc.ac.za
                ftanser@gmail.com
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                7 June 2019
                7 June 2019
                2019
                : 19
                : 500
                Affiliations
                [1 ]ISNI 0000 0000 9155 0024, GRID grid.415021.3, HIV Prevention Research Unit, , South African Medical Research Council, ; 123 Jan Hofmeyr Road, Westville, Durban, KwaZulu-Natal 3630 South Africa
                [2 ]ISNI 0000 0004 0425 469X, GRID grid.8991.9, Department of Epidemiology and Population Health, , London School of Hygiene and Tropical Medicine, ; London, UK
                [3 ]ISNI 0000000122986657, GRID grid.34477.33, School of Medicine, Department of Global Health, , University of Washington, ; Seattle, WA USA
                [4 ]ISNI 0000 0001 0723 4123, GRID grid.16463.36, School of Nursing and Public Health, , University of KwaZulu-Natal, ; Kwazulu-Natal, Durban, South Africa
                [5 ]ISNI 0000 0000 9155 0024, GRID grid.415021.3, Biostatistics Unit: GIS, South African Medical Research Council, ; Durban, KwaZulu-Natal South Africa
                [6 ]ISNI 0000 0004 4902 0432, GRID grid.1005.4, Kirby Institute, , University of New South Wales, ; Kensington, NSW 2052 Australia
                [7 ]ISNI 0000 0000 9155 0024, GRID grid.415021.3, Biostatistics Unit, , South African Medical Research Council, ; Durban, KwaZulu-Natal South Africa
                [8 ]GRID grid.488675.0, Africa Health Research Institute, ; Durban, Kwazulu-Natal South Africa
                [9 ]ISNI 0000000121901201, GRID grid.83440.3b, Research Department of Infection & Population Health, , University College London, ; London, UK
                [10 ]ISNI 0000 0001 0723 4123, GRID grid.16463.36, Centre for the AIDS Programme of Research in South Africa – CAPRISA, , University of KwaZulu-Natal, ; Durban, Congella South Africa
                Article
                4080
                10.1186/s12879-019-4080-6
                6555962
                31174475
                e1195534-881e-442e-84da-416a42a37720
                © The Author(s). 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 July 2018
                : 13 May 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Infectious disease & Microbiology
                hiv,spatial epidemiology,mapping,incidence,risk factors,heterogeneity

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