38 results on '"Boulle, Andrew"'
Search Results
2. Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia
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Nyemba, Dorothy C., Kalk, Emma, Vinikoor, Michael J., Madlala, Hlengiwe P., Mubiana-Mbewe, Mwangelwa, Mzumara, Maureen, Moore, Carolyn Bolton, Slogrove, Amy L., Boulle, Andrew, Davies, Mary-Ann, Myer, Landon, and Powis, Kathleen
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- 2022
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3. COVID-19 Vaccine Uptake and Effectiveness by Time since Vaccination in the Western Cape Province, South Africa: An Observational Cohort Study during 2020–2022.
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Kassanjee, Reshma, Davies, Mary-Ann, Heekes, Alexa, Mahomed, Hassan, Hawkridge, Anthony J., Morden, Erna, Jacobs, Theuns, Cohen, Cheryl, Moultrie, Harry, Lessells, Richard J., Van Der Walt, Nicolette, Arendse, Juanita O., Wolter, Nicole, Walaza, Sibongile, Jassat, Waasila, von Gottberg, Anne, Hannan, Patrick L., Feikin, Daniel R., Cloete, Keith, and Boulle, Andrew
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VACCINE effectiveness ,VACCINATION status ,COVID-19 vaccines ,BOOSTER vaccines ,VACCINATION - Abstract
There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine availability. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa, in an observational cohort study of >2 million adults during 2020–2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalization and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies, and healthcare utilization. We found that by the end of 2022, 41% of surviving adults had completed vaccination and 8% had received a booster dose. Recent vaccination was associated with notable reductions in severe COVID-19 during periods dominated by Delta, and Omicron BA.1/2 and BA.4/5 (sub)lineages. During the latest Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57–94 and 49–95, respectively). However, distinct reductions of effectiveness occurred at longer times post completing or boosting vaccination. Results highlight the importance of continued emphasis on COVID-19 vaccination and boosting for those at high risk of severe COVID-19, even in settings with widespread infection-induced immunity. [ABSTRACT FROM AUTHOR]
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- 2024
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4. ART history prior to conception: trends and association with postpartum disengagement from HIV care in Khayelitsha, South Africa (2013–2019): a retrospective cohort study.
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Phillips, Tamsin Kate, Kassanjee, Reshma, Maxwell, Nicola, Anderson, Kim, Johnson, Leigh, Moolla, Haroon, Myer, Landon, Chi, Benjamin H., Euvrard, Jonathan, Boulle, Andrew, Davies, Mary‐Ann, Cornell, Morna, and de Waal, Renee
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ART history ,PRENATAL care ,PUERPERIUM ,POSTNATAL care ,MATERNAL age ,PRECONCEPTION care - Abstract
Introduction: In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception. Methods: We analysed data from people living with HIV (aged 15–49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan–Meier curves and proportional‐hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum. Results: Among 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25–27%) had disengaged from care by 1 year and 34% (95% CI 33–36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70–2.60), restarted (C: aHR 3.32, 95% CI 2.70–4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12–2.74) had increased hazards of postpartum disengagement compared to those on ART (A). Conclusions: There is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care. [ABSTRACT FROM AUTHOR]
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- 2024
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5. The Continuing Burden of Advanced HIV Disease Over 10 Years of Increasing Antiretroviral Therapy Coverage in South Africa
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Osler, Meg, Hilderbrand, Katherine, Goemaere, Eric, Ford, Nathan, Smith, Mariette, Meintjes, Graeme, Kruger, James, Govender, Nelesh P., and Boulle, Andrew
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- 2018
6. Change in HIV‐related characteristics of children hospitalised with infectious diseases in Western Cape, South Africa, 2008–2021: a time trend analysis.
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de Beer, Shani T., Slogrove, Amy L., Eley, Brian, Ingle, Suzanne M., Jones, Hayley E., Phelanyane, Florence, Anderson, Kim, Kalk, Emma, Boulle, Andrew, and Davies, Mary‐Ann
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CHILD health services ,COMMUNICABLE diseases ,TUBERCULOUS meningitis ,TREND analysis ,HIV infection transmission ,RESPIRATORY infections - Abstract
Introduction: With the scaling up of vertical HIV transmission prevention programmes, the HIV‐related population profile of children in South Africa has shifted. We described temporal changes in HIV‐related characteristics of children, aged ≤3 years (up to the third birthday), with infectious disease hospitalisations across the Western Cape province. Methods: We used routinely collected electronic data to identify children born in the Western Cape with infectious disease hospital records for lower respiratory tract infections, diarrhoea, meningitis and tuberculous meningitis, from 2008 to 2021. Linked maternal and child unique identifiers were used to extract pregnancy, HIV‐related, laboratory, pharmacy and hospitalisation data. We described temporal changes in child HIV exposure and acquisition status, timing of maternal HIV diagnosis and antiretroviral therapy (ART) start, infant exposure to maternal ART and timing thereof, and maternal CD4 and HIV viral load closest to delivery. We used logistic and multinomial regression to assess changes in characteristics between the Pre‐Option B+ (2008–2013), Option B+ (2013–2016) and Universal ART periods (2016–2021). Results: Among 52,811 children aged ≤3 years with hospitalisations, the proportion living with HIV dreased from 7.0% (2008) to 1.1% (2021), while those exposed to HIV and uninfected increased from 14.0% (2008) to 16.1% (2021) with a peak of 18.3% in 2017. Among mothers with HIV (n = 9873), the proportion diagnosed with HIV and starting ART before pregnancy increased from 20.2% to 69.2% and 5.8% to 59.0%, respectively, between 2008 and 2021. Children hospitalised during the Universal ART period had eight times higher odds (Odds Ratio: 8.41; 95% CI: 7.36–9.61) of exposure to maternal ART versus children admitted Pre‐Option B+. Among mothers of children exposed to HIV and uninfected with CD4 records (n = 7523), the proportion with CD4 <350 cells/μl decreased from 90.6% (2008) to 27.8% (2021). Conclusions: In recent years, among children hospitalised with infectious diseases, there were fewer children with perinatally acquired HIV, while an increased proportion of those without HIV acquisition are exposed to maternal HIV and ART. There is a need to look beyond paediatric HIV prevalence and consider child exposure to HIV and ART among children without HIV, when assessing the HIV epidemic's impact on child health services. [ABSTRACT FROM AUTHOR]
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- 2023
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7. COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa
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Kassanjee, Reshma, Davies, Mary-Ann, Ngwenya, Olina, Osei-Yeboah, Richard, Jacobs, Theuns, Morden, Erna, Timmerman, Venessa, Britz, Stefan, Mendelson, Marc, Taljaard, Jantjie, Riou, Julien, Boulle, Andrew, Tiffin, Nicki, and Zinyakatira, Nesbert
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South Africa ,SARS-CoV-2 ,360 Social problems & social services ,HIV ,COVID-19 ,610 Medicine & health ,CD4 count ,mortality - Abstract
Introduction While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH. Methods We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. Results Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. Conclusions Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.
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- 2023
8. Trends in maternal and neonatal mortality in South Africa: a systematic review
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Damian, Damian J., Njau, Bernard, Lisasi, Ester, Msuya, Sia E., and Boulle, Andrew
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- 2019
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9. The impact of HIV and tuberculosis interventions on South African adult tuberculosis trends, 1990-2019: a mathematical modeling analysis
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Kubjane, Mmamapudi, Osman, Muhammad, Boulle, Andrew, and Johnson, Leigh F.
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Microbiology (medical) ,Adult ,South Africa ,Infectious Diseases ,Incidence ,Isoniazid ,Humans ,Tuberculosis ,Bayes Theorem ,HIV Infections ,General Medicine ,Q1 - Abstract
Objectives: To quantify the South African adult tuberculosis (TB) incidence and mortality attributable to HIV between 1990 and 2019 and to estimate the reduction in TB incidence due to directly observed therapy, antiretroviral therapy (ART), isoniazid preventive therapy, increased TB screening, and Xpert MTB/RIF.\ud Methods: We developed a dynamic TB transmission model for South Africa. A Bayesian approach was used to calibrate the model to South African-specific data sources. Counterfactual scenarios were simulated to estimate TB incidence and mortality attributable to HIV and the impact of interventions on TB\ud incidence.\ud Results: Between 1990 and 2019, 8.8 million (95% confidence interval [CI] 8.3-9.3 million) individuals developed TB, and 2.1 million (95% CI 2.0-2.2 million) died from TB. A total of 55% and 69% of TB cases and\ud mortality were due to HIV, respectively. Overall, TB screening and ART substantially reduced TB incidence by 28.2% (95% CI 26.4-29.8%) and 20.0% (95% CI 19.2-20.7%), respectively, in 2019; other interventions had\ud minor impacts.\ud Conclusion: HIV has dramatically increased TB incidence and mortality in South Africa. The provision of ART and intensification of TB screening explained most recent declines in TB incidence.
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- 2022
10. Risk Factors for Coronavirus Disease 2019 (COVID-19) Death in a Population Cohort Study from the Western Cape Province, South Africa
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Boulle, Andrew, Davies, Mary-Ann, Hussey, Hannah, Ismail, Muzzammil, Morden, Erna, Vundle, Ziyanda, Zweigenthal, Virginia, Mahomed, Hassan, Paleker, Masudah, Pienaar, David, Tembo, Yamanya, Lawrence, Charlene, Isaacs, Washiefa, Mathema, Hlengani, Allen, Derick, Allie, Taryn, Bam, Jamy-Lee, Buddiga, Kasturi, Dane, Pierre, Heekes, Alexa, Matlapeng, Boitumelo, Mutemaringa, Themba, Muzarabani, Luckmore, Phelanyane, Florence, Pienaar, Rory, Rode, Catherine, Smith, Mariette, Tiffin, Nicki, Zinyakatira, Nesbert, Cragg, Carol, Marais, Frederick, Mudaly, Vanessa, Voget, Jacqueline, Davids, Jody, Roodt, Francois, van Zyl Smit, Nellis, Vermeulen, Alda, Adams, Kevin, Audley, Gordon, Bateman, Kathleen, Beckwith, Peter, Bernon, Marc, Blom, Dirk, Boloko, Linda, Botha, Jean, Boutall, Adam, Burmeister, Sean, Cairncross, Lydia, Calligaro, Gregory, Coccia, Cecilia, Corin, Chadwin, Daroowala, Remy, Dave, Joel A, De Bruyn, Elsa, De Villiers, Martin, Deetlefs, Mimi, Dlamini, Sipho, Du Toit, Thomas, Endres, Wilhelm, Europa, Tarin, Fieggan, Graham, Figaji, Anthony, Frankenfeld, Petro, Gatley, Elizabeth, Gina, Phindile, Govender, Evashan, Grobler, Rochelle, Gule, Manqoba Vusumuzi, Hanekom, Christoff, Held, Michael, Heynes, Alana, Hlatswayo, Sabelo, Hodkinson, Bridget, Holtzhausen, Jeanette, Hoosain, Shakeel, Jacobs, Ashely, Kahn, Miriam, Kahn, Thania, Khamajeet, Arvin, Khan, Joubin, Khan, Riaasat, Khwitshana, Alicia, Knight, Lauren, Kooverjee, Sharita, Krogscheepers, Rene, Kruger, Jean Jacque, Kuhn, Suzanne, Laubscher, Kim, Lazarus, John, Le Roux, Jacque, Lee Jones, Scott, Levin, Dion, Maartens, Gary, Majola, Thina, Manganyi, Rodgers, Marais, David, Marais, Suzaan, Maritz, Francois, Maughan, Deborah, Mazondwa, Simthandile, Mbanga, Luyanda, Mbatani, Nomonde, Mbena, Bulewa, Meintjes, Graeme, Mendelson, Marc, Möller, Ernst, Moore, Allison, Ndebele, Babalwa, Nortje, Marc, Ntusi, Ntobeko, Nyengane, Funeka, Ofoegbu, Chima, Papavarnavas, Nectarios, Peter, Jonny, Pickard, Henri, Pluke, Kent, Raubenheimer, Peter J, Robertson, Gordon, Rozmiarek, Julius, Sayed, A, Scriba, Matthias, Sekhukhune, Hennie, Singh, Prasun, Smith, Elsabe, Soldati, Vuyolwethu, Stek, Cari, van den berg, Robert, van der Merwe, Le Roux, Venter, Pieter, Vermooten, Barbra, Viljoen, Gerrit, Viranna, Santhuri, Vogel, Jonno, Vundla, Nokubonga, Wasserman, Sean, Zitha, Eddy, Lomas-Marais, Vanessa, Lombard, Annie, Stuve, Katrin, Viljoen, Werner, Basson, De Vries, Le Roux, Sue, Linden-Mars, Ethel, Victor, Lizanne, Wates, Mark, Zwanepoel, Elbe, Ebrahim, Nabilah, Lahri, Sa’ad, Mnguni, Ayanda, Crede, Thomas, de Man, Martin, Evans, Katya, Hendrikse, Clint, Naude, Jonathan, Parak, Moosa, Szymanski, Patrick, Van Koningsbruggen, Candice, Abrahams, Riezaah, Allwood, Brian, Botha, Christoffel, Botha, Matthys Henndrik, Broadhurst, Alistair, Claasen, Dirkie, Daniel, Che, Dawood, Riyaadh, du Preez, Marie, Du Toit, Nicolene, Erasmus, Kobie, Koegelenberg, Coenraad F N, Gabriel, Shiraaz, Hugo, Susan, Jardine, Thabiet, Johannes, Clint, Karamchand, Sumanth, Lalla, Usha, Langenegger, Eduard, Louw, Eize, Mashigo, Boitumelo, Mhlana, Nonte, Mnqwazi, Chizama, Moodley, Ashley, Moodley, Desiree, Moolla, Saadiq, Mowlana, Abdurasiet, Nortje, Andre, Olivier, Elzanne, Parker, Arifa, Paulsen, Chané, Prozesky, Hans, Rood, Jacques, Sabela, Tholakele, Schrueder, Neshaad, Sithole, Nokwanda, Sithole, Sthembiso, Taljaard, Jantjie J, Titus, Gideon, Van Der Merwe, Tian, van Schalkwyk, Marije, Vazi, Luthando, Viljoen, Abraham J, Yazied Chothia, Mogamat, Naidoo, Vanessa, Wallis, Lee Alan, Abbass, Mumtaz, Arendse, Juanita, Armien, Rizqa, Bailey, Rochelle, Bello, Muideen, Carelse, Rachel, Forgus, Sheron, Kalawe, Nosi, Kariem, Saadiq, Kotze, Mariska, Lucas, Jonathan, McClaughlin, Juanita, Murie, Kathleen, Najjaar, Leilah, Petersen, Liesel, Porter, James, Shaw, Melanie, Stapar, Dusica, Williams, Michelle, Aldum, Linda, Berkowitz, Natacha, Girran, Raakhee, Lee, Kevin, Naidoo, Lenny, Neumuller, Caroline, Anderson, Kim, Begg, Kerrin, Boerlage, Lisa, Cornell, Morna, de Waal, Renée, Dudley, Lilian, English, René, Euvrard, Jonathan, Groenewald, Pam, Jacob, Nisha, Jaspan, Heather, Kalk, Emma, Levitt, Naomi, Malaba, Thoko, Nyakato, Patience, Patten, Gabriela, Schneider, Helen, Shung King, Maylene, Tsondai, Priscilla, Van Duuren, James, van Schaik, Nienke, Blumberg, Lucille, Cohen, Cheryl, Govender, Nelesh, Jassat, Waasila, Kufa, Tendesayi, McCarthy, Kerrigan, Morris, Lynn, Hsiao, Nei-yuan, Marais, Ruan, Ambler, Jon, Ngwenya, Olina, Osei-Yeboah, Richard, Johnson, Leigh, Kassanjee, Reshma, and Tamuhla, Tsaone
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sub-Saharan Africa ,0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,Tuberculosis ,antiretroviral ,030106 microbiology ,Population ,HIV Infections ,HIV Infections/complications ,Cohort Studies ,South Africa ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Major Article ,Medicine ,Humans ,030212 general & internal medicine ,education ,Proportional Hazards Models ,education.field_of_study ,South Africa/epidemiology ,business.industry ,Proportional hazards model ,SARS-CoV-2 ,Hazard ratio ,HIV ,Correction ,COVID-19 ,medicine.disease ,Confidence interval ,AcademicSubjects/MED00290 ,Infectious Diseases ,Standardized mortality ratio ,tuberculosis ,Attributable risk ,business ,Viral load ,Demography - Abstract
Background Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. Methods We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates. Results Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID-19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1). Conclusions While our findings may overestimate HIV- and tuberculosis-associated COVID-19 mortality risks due to residual confounding, both living with HIV and having current tuberculosis were independently associated with increased COVID-19 mortality. The associations between age, sex, and other comorbidities and COVID-19 mortality were similar to those in other settings.
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- 2021
11. Antiretroviral Adherence Interventions in Southern Africa: Implications for Using HIV Treatments for Prevention
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Dewing, Sarah, Mathews, Cathy, Fatti, Geoffrey, Grimwood, Ashraf, and Boulle, Andrew
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- 2014
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12. Changing contextual factors from baseline to 9-months post-HIV diagnosis predict 5-year mortality in Durban, South Africa.
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Bassett, Ingrid V., Xu, Ai, Giddy, Janet, Bogart, Laura M., Boulle, Andrew, Millham, Lucia, Losina, Elena, and Parker, Robert A.
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MORTALITY risk factors ,HIV infections ,SOCIAL support ,HEALTH services accessibility ,TIME ,AGE distribution ,ANTIRETROVIRAL agents ,MENTAL health ,SEX distribution ,SURVIVAL analysis (Biometry) ,PSYCHOLOGY of HIV-positive persons ,SECONDARY analysis ,PROPORTIONAL hazards models - Abstract
Changes in an individual's contextual factors following HIV diagnosis may influence long-term outcomes. We evaluated how changes to contextual factors between HIV diagnosis and 9-month follow-up predict 5-year mortality among HIV-infected individuals in Durban, South Africa enrolled in the Sizanani Trial (NCT01188941). We used random survival forests to identify 9-month variables and changes from baseline predictive of time to mortality. We incorporated these into a Cox proportional hazards model including age, sex, and starting ART by 9 months a priori, 9-month social support and competing needs, and changes in mental health between baseline and 9 months. Among 1,154 participants with South African ID numbers, 900 (78%) had baseline and 9-month data available of whom 109 (12%) died after 9-month follow-up. Those who reported less social support at 9 months had a 16% higher risk of mortality. Participants who went without basic needs or healthcare at 9 months had a 2.6 times higher hazard of death compared to participants who did not. Low social support and competing needs at 9-month follow-up substantially increase long-term mortality risk. Reassessing contextual factors during follow-up and targeting interventions to increase social support and affordability of care may reduce long-term mortality for HIV-infected individuals in South Africa. [ABSTRACT FROM AUTHOR]
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- 2021
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13. High Rates of Recurrent Tuberculosis Disease: A Population-level Cohort Study.
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Hermans, Sabine M, Zinyakatira, Nesbert, Caldwell, Judy, Cobelens, Frank G J, Boulle, Andrew, and Wood, Robin
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TUBERCULOSIS epidemiology ,DRUG therapy for tuberculosis ,TUBERCULOSIS risk factors ,HIV infections ,CONFIDENCE intervals ,HEALTH status indicators ,DISEASE incidence ,REINFECTION ,DISEASE relapse ,RISK assessment ,DESCRIPTIVE statistics ,ANTITUBERCULAR agents ,LONGITUDINAL method ,PROBABILITY theory ,DISEASE complications - Abstract
Background Retreatment tuberculosis (TB) disease is common in high-prevalence settings. The risk of repeated episodes of recurrent TB is unknown. We calculated the rate of recurrent TB per subsequent episode by matching individual treatment episodes over a period of 13 years. Methods All recorded TB episodes in Cape Town between 2003 and 2016 were matched by probabilistic linkage of personal identifiers. Among individuals with a first episode notified in Cape Town and who completed their prior treatment successfully we estimated the recurrence rate stratified by subsequent episode and HIV status. We adjusted person-time to background mortality by age, sex, and HIV status. Results A total of 292 915 TB episodes among 263 848 individuals were included. The rate of recurrent TB was 16.4 per 1000 person-years (95% CI, 16.2–16.6), and increased per subsequent episode (8.4-fold increase, from 14.6 to 122.7 per 1000 from episode 2 to 6, respectively). These increases were similar stratified by HIV status. Rates among HIV positives were higher than among HIV negatives for episodes 2 and 3 (2- and 1.5-fold higher, respectively), and the same thereafter. Conclusions TB recurrence rates were high and increased per subsequent episode, independent of HIV status. This suggests that HIV infection is insufficient to explain the high burden of recurrence; it is more likely due to a high annual risk of infection combined with an increased risk of infection or progression to disease associated with a previous TB episode. The very high recurrence rates would justify increased TB surveillance of patients with >1 episode. [ABSTRACT FROM AUTHOR]
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- 2021
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14. Assessing the association between changing NRTIs when initiating second-line ART and treatment outcomes
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Rohr, Julia K, Ive, Prudence, Horsburgh, C Robert, Berhanu, Rebecca, Hoffmann, Christopher J, Wood, Robin, Boulle, Andrew, Giddy, Janet, Prozesky, Hans, Vinikoor, Michael, Mwanza, Mwanza Wa, Wandeler, Gilles, Davies, Mary-Ann, and Fox, Matthew P
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Adult ,Male ,Adolescent ,Anti-HIV Agents ,Zambia ,610 Medicine & health ,HIV Infections ,Article ,South Africa ,Young Adult ,360 Social problems & social services ,immune system diseases ,Antiretroviral Therapy, Highly Active ,Humans ,Aged ,Aged, 80 and over ,Salvage Therapy ,virus diseases ,Middle Aged ,Viral Load ,CD4 Lymphocyte Count ,Treatment Outcome ,Reverse Transcriptase Inhibitors ,Female - Abstract
BACKGROUND After first-line antiretroviral therapy (ART) failure, the importance of change in nucleoside reverse transcriptase inhibitor (NRTI) in second-line is uncertain due to the high potency of protease inhibitors used in second-line. SETTING We used clinical data from 6,290 adult patients in South Africa and Zambia from the International Epidemiologic Databases to Evaluate AIDS-Southern Africa cohort. METHODS We included patients who initiated on standard first-line ART and had evidence of first-line failure. We used propensity score-adjusted Cox proportional hazards models to evaluate the impact of change in NRTI on second-line failure compared to remaining on the same NRTI in second-line. In South Africa, where viral load monitoring was available, treatment failure was defined as two consecutive viral loads >1,000 copies/mL. In Zambia, it was defined as two consecutive CD4 counts
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- 2018
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15. High rates of retention and viral suppression in the scale-up of antiretroviral therapy adherence clubs in Cape Town, South Africa
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Tsondai, Priscilla Ruvimbo, Wilkinson, Lynne Susan, Grimsrud, Anna, Mdlalo, Precious Thembekile, Ullauri, Angelica, and Boulle, Andrew
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Adult ,Male ,retention ,Adolescent ,Anti-HIV Agents ,antiretroviral therapy ,HIV ,HIV Infections ,Middle Aged ,Viral Load ,Article ,models of care ,program outcomes ,Medication Adherence ,Cohort Studies ,South Africa ,Young Adult ,Cross-Sectional Studies ,Humans ,Female ,adherence club ,Research Article ,Proportional Hazards Models ,Retrospective Studies - Abstract
Introduction: Increasingly, there is a need for health authority scale up of successfully piloted differentiated models of antiretroviral therapy (ART) delivery. However, there is a paucity of evidence on system-wide outcomes after scale-up. In the Cape Town health district, stable adult patients were referred to adherence clubs (ACs) – a group model of ART delivery with five visits per year. By the end of March 2015, over 32,000 ART patients were in an AC. We describe patient outcomes of a representative sample of AC patients during this scale-up. Methods: Patients enrolled in an AC at non-research supported sites between 2011 and 2014 were eligible for analysis. We sampled 10% of ACs (n = 100) in quintets proportional to the number of ACs at each facility, linking each patient to city-wide laboratory and service access data to validate retention and virologic outcomes. We digitized registers and used competing risks regression and cross-sectional methods to estimate outcomes: mortality, transfers, loss to follow-up (LTFU) and viral load suppression (≤400 copies/mL). Predictors of LTFU and viral rebound were assessed using Cox proportional hazards models. Results: Of the 3216 adults contributing 4019 person years of follow-up (89% in an AC, median 1.1 years), 70% were women. Retention was 95.2% (95% CI, 94.0-96.4) at 12 months and 89.3% (95% CI, 87.1-91.4) at 24 months after AC enrolment. In the 13 months prior to analysis closure, 88.1% of patients had viral load assessments and of those, viral loads ≤400 copies/mL were found in 97.2% (95% CI, 96.5-97.8) of patients. Risk of LTFU was higher in younger patients and in patients accessing ART from facilities with larger ART cohorts. Risk of viral rebound was higher in younger patients, those that had been on ART for longer and patients that had never sent a buddy to collect their medication. Conclusions: This is the first analysis reporting patient outcomes after health authorities scaled-up a differentiated care model across a high burden district. The findings provide substantial reassurance that stable patients on long-term ART can safely be offered care options, which are more convenient to patients and less burdensome to services.
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- 2017
16. Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study
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Johnson, Leigh F, May, Margaret T, Cornell, Morna, Boulle, Andrew, Egger, Matthias, Davies, Mary-Ann, Centre for Infectious Disease Epidemiology and Research, and Faculty of Health Sciences
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AIDS ,South Africa ,Death rates ,HIV epidemiology ,HIV ,Tuberculosis ,HIV diagnosis and management ,Antiretroviral therapy - Abstract
Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART.
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- 2017
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17. Population‐wide differentials in HIV service access and outcomes in the Western Cape for men as compared to women, South Africa: 2008 to 2018: a cohort analysis.
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Osler, Meg, Cornell, Morna, Ford, Nathan, Hilderbrand, Katherine, Goemaere, Eric, and Boulle, Andrew
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HEALTH services accessibility ,HIV-positive men ,HIV-positive women ,ANTIRETROVIRAL agents ,MEDICAL care ,CD4 lymphocyte count ,COHORT analysis ,PROPORTIONAL hazards models - Abstract
Introduction: Few studies have systematically described population‐level differences comparing men and women across the continuum of routine HIV care. This study quantifies differentials in HIV care, treatment and mortality outcomes for men and women over time in South Africa. Methods: We analysed population‐wide linked anonymized data, including vital registration linkage, for the Western Cape Province, from the time of first CD4 count. Three antiretroviral therapy guideline eligibility periods were defined: 1 January 2008 to 31 July 2011 (CD4 cell count <200 cells/µL), 1 August 2011 to 31 December 2014 (<350 cells/µL), 1 January 2015 to 31 August 2016 (<500 cells/µL). We estimated care uptake based on service attendance, and modelled associations for men and women with ART initiation and overall, pre‐ART and ART mortality. Separate Cox proportional hazard models were built for each outcome and eligibility period, adjusted for tuberculosis, pregnancy, CD4 count and age. Results: Adult men made up 49% of the population and constituted 37% of those living with HIV. In 2009, 46% of men living with HIV attended health services, rising to 67% by 2015 compared to 54% and 77% of women respectively. Men contributed <35% of all CD4 cell counts over 10 years and presented with more advanced disease (39% of all first presentation CD4 cell counts from men were <200 cells/µL compared to 25% in women). ART access was lower in men compared to women (AHR 0.79 (0.77 to 0.80) summarized for Period 2) over the entire study). Mortality was greater in men irrespective of ART (AHR 1.08 (1.01 to 1.16) Period 3) and after ART start (AHR 1.15 (1.05 to 1.20) Period 3) with mortality differences decreasing over time. Conclusions: Compared to women, men presented with more advanced disease, were less likely to attend health care services annually, were less likely to initiate ART and had higher mortality overall and while receiving ART care. People living with HIV were more likely to initiate ART if they had acute reasons to access healthcare beyond HIV, such as being pregnant or being co‐infected with tuberculosis. Our findings point to missed opportunities for improving access to and outcomes from interventions for men along the entire HIV cascade. [ABSTRACT FROM AUTHOR]
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- 2020
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18. Quantifying the HIV treatment cascade in a South African health sub-district by gender: retrospective cohort study.
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Lurie, Mark N., Kirwa, Kipruto, Callaway, Julia, Cornell, Morna, Boulle, Andrew, Bengtson, Angela M., Smith, Mariette, Leon, Natalie, and Colvin, Christopher
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CD4 lymphocyte count ,HIV ,COHORT analysis ,GENDER - Abstract
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- 2020
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19. Stock-outs of antiretroviral and tuberculosis medicines in South Africa: A national cross-sectional survey.
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Hwang, Bella, Shroufi, Amir, Gils, Tinne, Steele, Sarah Jane, Grimsrud, Anna, Boulle, Andrew, Yawa, Anele, Stevenson, Sasha, Jankelowitz, Lauren, Versteeg-Mojanaga, Marije, Govender, Indira, Stephens, John, Hill, Julia, Duncan, Kristal, and van Cutsem, Gilles
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MULTIDRUG-resistant tuberculosis ,RIFAMPIN ,HEALTH facilities ,DRUGS ,INVENTORY shortages - Abstract
Background: HIV and TB programs have rapidly scaled-up over the past decade in Sub-Saharan Africa and uninterrupted supplies of those medicines are critical to their success. However, estimates of stock-outs are largely unknown. This survey aimed to estimate the extent of stock-outs of antiretroviral and TB medicines in public health facilities across South Africa, which has the world’s largest antiretroviral treatment (ART) program and a rising multidrug-resistant TB epidemic. Methods: We conducted a cross-sectional telephonic survey (October—December 2015) of public health facilities. Facilities were asked about the prevalence of stock-outs on the day of the survey and in the preceding three months, their duration and impact. Results: Nationwide, of 3547 eligible health facilities, 79% (2804) could be reached telephonically. 88% (2463) participated and 4% (93) were excluded as they did not provide ART or TB treatment. Of the 2370 included facilities, 20% (485) reported a stock-out of at least 1 ARV and/or TB-related medicine on the day of contact and 36% (864) during the three months prior to contact, ranging from 74% (163/220) of health facilities in Mpumalanga to 12% (32/261) in the Western Cape province. These 864 facilities reported 1475 individual stock-outs, with one to fourteen different medicines out of stock per facility. Information on impact was provided in 98% (1449/1475) of stock-outs: 25% (366) resulted in a high impact outcome, where patients left the facility without medicine or were provided with an incomplete regimen. Of the 757 stock-outs that were resolved 70% (527) lasted longer than one month. Interpretation: There was a high prevalence of stock-outs nationwide. Large interprovincial differences in stock-out occurrence, duration, and impact suggest differences in provincial ability to prevent, mitigate and cope within the same framework. End-user monitoring of the supply chain by patients and civil society has the potential to increase transparency and complement public sector monitoring systems. [ABSTRACT FROM AUTHOR]
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- 2019
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20. Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.
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Johnson, Leigh F., May, Margaret T., Dorrington, Rob E., Cornell, Morna, Boulle, Andrew, Egger, Matthias, and Davies, Mary-Ann
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ANTIRETROVIRAL agents ,MORTALITY ,HIV infections ,PUBLIC health ,TREATMENT effectiveness ,HIV infection transmission ,MATHEMATICAL models ,PROBABILITY theory ,RESEARCH funding ,THEORY ,HIGHLY active antiretroviral therapy - Abstract
Background: Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART.Methods and Findings: Model estimates of mortality rates in ART patients were obtained from the International Epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration. The model was calibrated to HIV prevalence data (1997-2013) and mortality data from the South African vital registration system (1997-2014), using a Bayesian approach. In the 1985-2014 period, 2.70 million adult HIV-related deaths occurred in South Africa. Adult HIV deaths peaked at 231,000 per annum in 2006 and declined to 95,000 in 2014, a reduction of 74.7% (95% CI: 73.3%-76.1%) compared to the scenario without ART. However, HIV mortality in 2014 was estimated to be 69% (95% CI: 46%-97%) higher in 2014 (161,000) if the model was calibrated only to HIV prevalence data. In the 2000-2014 period, the South African ART programme is estimated to have reduced the cumulative number of HIV deaths in adults by 1.72 million (95% CI: 1.58 million-1.84 million) and to have saved 6.15 million life years in adults (95% CI: 5.52 million-6.69 million). This compares with a potential saving of 8.80 million (95% CI: 7.90 million-9.59 million) life years that might have been achieved if South Africa had moved swiftly to implement WHO guidelines (2004-2013) and had achieved high levels of ART uptake in HIV-diagnosed individuals from 2004 onwards. The model is limited by its reliance on all-cause mortality data, given the lack of reliable cause-of-death reporting, and also does not allow for changes over time in tuberculosis control programmes and ART effectiveness.Conclusions: ART has had a dramatic impact on adult mortality in South Africa, but delays in the rollout of ART, especially in the early stages of the ART programme, have contributed to substantial loss of life. This is the first study to our knowledge to calibrate a model of ART impact to population-level recorded death data in Africa; models that are not calibrated to population-level death data may overestimate HIV-related mortality. [ABSTRACT FROM AUTHOR]- Published
- 2017
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21. Contemporary disengagement from antiretroviral therapy in Khayelitsha, South Africa: A cohort study.
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Kaplan, Samantha R., Oosthuizen, Christa, Stinson, Kathryn, Little, Francesca, Euvrard, Jonathan, Schomaker, Michael, Osler, Meg, Hilderbrand, Katherine, Boulle, Andrew, and Meintjes, Graeme
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THERAPEUTICS ,HIV infections ,HIGHLY active antiretroviral therapy ,PROPORTIONAL hazards models ,HEALTH outcome assessment ,HIV-positive persons ,MEDICAL care ,ANTIRETROVIRAL agents ,HIV infection epidemiology ,AGE distribution ,DRUGS ,PATIENT compliance ,SEX distribution ,DISEASE incidence ,ACQUISITION of data ,RETROSPECTIVE studies ,PATIENTS' attitudes - Abstract
Background: Retention in care is an essential component of meeting the UNAIDS "90-90-90" HIV treatment targets. In Khayelitsha township (population ~500,000) in Cape Town, South Africa, more than 50,000 patients have received antiretroviral therapy (ART) since the inception of this public-sector program in 2001. Disengagement from care remains an important challenge. We sought to determine the incidence of and risk factors associated with disengagement from care during 2013-2014 and outcomes for those who disengaged.Methods and Findings: We conducted a retrospective cohort study of all patients ≥10 years of age who visited 1 of the 13 Khayelitsha ART clinics from 2013-2014 regardless of the date they initiated ART. We described the cumulative incidence of first disengagement (>180 days not attending clinic) between 1 January 2013 and 31 December 2014 using competing risks methods, enabling us to estimate disengagement incidence up to 10 years after ART initiation. We also described risk factors for disengagement based on a Cox proportional hazards model, using multiple imputation for missing data. We ascertained outcomes (death, return to care, hospital admission, other hospital contact, alive but not in care, no information) after disengagement until 30 June 2015 using province-wide health databases and the National Death Registry. Of 39,884 patients meeting our eligibility criteria, the median time on ART to 31 December 2014 was 33.6 months (IQR 12.4-63.2). Of the total study cohort, 592 (1.5%) died in the study period, 1,231 (3.1%) formally transferred out, 987 (2.5%) were silent transfers and visited another Western Cape province clinic within 180 days, 9,005 (22.6%) disengaged, and 28,069 (70.4%) remained in care. Cumulative incidence of disengagement from care was estimated to be 25.1% by 2 years and 50.3% by 5 years on ART. Key factors associated with disengagement (age, male sex, pregnancy at ART start [HR 1.58, 95% CI 1.47-1.69], most recent CD4 count) and retention (ART club membership, baseline CD4) after adjustment were similar to those found in previous studies; however, notably, the higher hazard of disengagement soon after starting ART was no longer present after adjusting for these risk factors. Of the 9,005 who disengaged, the 2 most common initial outcomes were return to ART care after 180 days (33%; n = 2,976) and being alive but not in care in the Western Cape (25%; n = 2,255). After disengagement, a total of 1,459 (16%) patients were hospitalized and 237 (3%) died. The median follow-up from date of disengagement to 30 June 2015 was 16.7 months (IQR 11-22.4). As we included only patient follow-up from 2013-2014 by design in order to maximize the generalizability of our findings to current programs, this limited our ability to more fully describe temporal trends in first disengagement.Conclusions: Twenty-three percent of ART patients in the large cohort of Khayelitsha, one of the oldest public-sector ART programs in South Africa, disengaged from care at least once in a contemporary 2-year period. Fifty-eight percent of these patients either subsequently returned to care (some "silently") or remained alive without hospitalization, suggesting that many who are considered "lost" actually return to care, and that misclassification of "lost" patients is likely common in similar urban populations. A challenge to meeting ART retention targets is developing, testing, and implementing program designs to target mobile populations and retain them in lifelong care. This should be guided by risk factors for disengagement and improving interlinkage of routine information systems to better support patient care across complex care platforms. [ABSTRACT FROM AUTHOR]- Published
- 2017
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22. Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration
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Davies Mary-Ann, Moultrie Harry, Eley Brian, Rabie Helena, Van Cutsem Gilles, Giddy Janet, Wood Robin, Technau Karl, Keiser Olivia, Egger Matthias, Boulle Andrew, and International Epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) Collaboration
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Male ,medicine.medical_specialty ,Pediatrics ,Nevirapine ,Efavirenz ,Anti-HIV Agents ,HIV Infections ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,South Africa ,0302 clinical medicine ,Pregnancy ,Antiretroviral Therapy, Highly Active ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Treatment Failure ,Child ,Salvage Therapy ,0303 health sciences ,Ritonavir ,030306 microbiology ,business.industry ,Hazard ratio ,Infant ,Lopinavir ,Viral Load ,Confidence interval ,3. Good health ,Surgery ,CD4 Lymphocyte Count ,Regimen ,Infectious Diseases ,chemistry ,Child, Preschool ,Female ,Drug Monitoring ,business ,Viral load ,medicine.drug - Abstract
Article approval pending, With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa.
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- 2011
23. Trends in maternal and neonatal mortality in South Africa: a systematic review protocol.
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Damian, Damian J., Njau, Bernard, Lisasi, Ester, Msuya, Sia E., and Boulle, Andrew
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NEONATAL mortality ,PUBLIC health - Abstract
Background: Measuring and monitoring progress towards Millennium Development Goals (MDG) 4 and 5 requires valid and reliable estimates of maternal and neonatal mortality. In South Africa, there are conflicting reports on the estimates of maternal and neonatal mortality, derived from both direct and indirect estimation techniques. This study aims to systematically review the estimates made of maternal and neonatal mortality in the period from 1990 to 2015 in South Africa and determine trends over this period. Methods: For the purpose of this review, searches for eligible studies will be conducted in MEDLINE, Africa-Wide Information, African Index Medicus, African Journals Online, Scopus, Web of Science and CINAHL databases. Searches will be restricted to articles written in English and presenting data covering the period between 1990 and 2015. Reference lists of retrieved articles will also be screened for additional publications. Three independent reviewers will be involved in the study selection, data extractions and achieving consensus. Study quality and risk of bias will thereafter be assessed by two authors. The results will be presented as rates/ratio with their corresponding 95% confidence/uncertainty intervals. Discussion: Identifying trends in maternal and neonatal mortality will help to track progress in MDGs 4 and 5 and will serve in evaluating interventions focusing on reducing maternal and child mortality in the country. This study will, in particular, provide the context for understanding inconsistencies in reported estimates of maternal and neonatal mortality by considering estimation methods, data sources and definitions used. Systematic review registration: PROSPERO [ABSTRACT FROM AUTHOR]
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- 2017
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24. Prospects for HIV control in South Africa: a model-based analysis.
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Johnson, Leigh F., Chiu, Calvin, Myer, Landon, Davies, Mary-Ann, Dorrington, Rob E., Bekker, Linda-Gail, Boulle, Andrew, and Meyer-Rath, Gesine
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HIV prevention ,PREVENTION of infectious disease transmission ,ANTIRETROVIRAL agents ,VERTICAL transmission (Communicable diseases) ,HIV infection epidemiology ,CIRCUMCISION ,CONDOMS ,STATISTICAL correlation ,COUNSELING ,STATISTICAL models ,PREVENTION - Abstract
Background: The goal of virtual elimination of horizontal and mother-to-child HIV transmission in South Africa (SA) has been proposed, but there have been few systematic investigations of which interventions are likely to be most critical to reducing HIV incidence. Objective: This study aims to evaluate SA's potential to achieve virtual elimination targets and to identify which interventions will be most critical to achieving HIV incidence reductions. Design: A mathematical model was developed to simulate the population-level impact of different HIV interventions in SA. Probability distributions were specified to represent uncertainty around 32 epidemiological parameters that could be influenced by interventions, and correlation coefficients (r) were calculated to assess the sensitivity of the adult HIV incidence rates and mother-to-child transmission rates (2015-2035) to each epidemiological parameter. Results: HIV incidence in SA adults (ages 15-49) is expected to decline from 1.4% in 2011-2012 to 0.29% by 2035 (95% CI: 0.10-0.62%). The parameters most strongly correlated with future adult HIV incidence are the rate of viral suppression after initiating antiretroviral treatment (ART) (r = -0.56), the level of condom use in non-marital relationships (r = -0.40), the phase-in of intensified risk-reduction counselling for HIV- positive adults (r = 0.29), the uptake of medical male circumcision (r = -0.24) and the phase-in of universal ART eligibility (r = 0.22). The paediatric HIV parameters most strongly associated with mother-to-child transmission rates are the relative risk of transmission through breastfeeding when the mother is receiving ART (r = 0.70) and the rate of ART initiation during pregnancy (r = -0.16). Conclusions: The virtual elimination target of a 0.1% incidence rate in adults will be difficult to achieve. Interventions that address the infectiousness of patients after ART initiation will be particularly critical to achieving long-term HIV incidence declines in South Africa. [ABSTRACT FROM AUTHOR]
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- 2016
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25. Temporal trends in TB notification rates during ART scale-up in Cape Town: an ecological analysis.
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Hermans, Sabine, Boulle, Andrew, Caldwell, Judy, Pienaar, David, and Wood, Robin
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Introduction: Although antiretroviral therapy (ART) reduces individual tuberculosis (TB) risk by two‐thirds, the population‐level impact remains uncertain. Cape Town reports high TB notification rates associated with endemic HIV. We examined population trends in TB notification rates during a 10‐year period of expanding ART. Methods: Annual Cape Town TB notifications were used as numerators and mid‐year Cape Town populations as denominators. HIV‐stratified population was calculated using overall HIV prevalence estimates from the Actuarial Society of South Africa AIDS and Demographic model. ART provision numbers from Western Cape government reports were used to calculate overall ART coverage. We calculated rates per 100,000 population over time, overall and stratified by HIV status. Rates per 100,000 total population were also calculated by ART use at treatment initiation. Absolute numbers of notifications were compared by age and sub‐district. Changes over time were described related to ART provision in the city as a whole (ART coverage) and by sub‐district (numbers on ART). Results: From 2003 to 2013, Cape Town's population grew from 3.1 to 3.7 million inhabitants, and estimated HIV prevalence increased from 3.6 to 5.2%. ART coverage increased from 0 to 63% in 2013. TB notification rates declined by 16% (95% confidence interval (CI), 14–17%) from a 2008 peak (851/100,000) to a 2013 nadir (713/100,000). Decreases were higher among the HIV‐positive (21% (95% CI, 19–23%)) than the HIV‐negative (9% (95% CI, 7–11%)) population. The number of HIV‐positive TB notifications decreased mainly among 0‐ to 4‐ and 20‐ to 34‐year‐olds. Total population rates on ART at TB treatment initiation increased over time but levelled off in 2013. Overall median CD4 counts increased from 146 cells/µl (interquartile range (IQR), 66, 264) to 178 cells/µl (IQR 75, 330; p <0.001). Sub‐district antenatal HIV seroprevalence differed (10–33%) as did numbers on ART (9–29 thousand). Across sub‐districts, infant HIV‐positive TB decreased consistently whereas adult decreases varied. Conclusions: HIV‐positive TB notification rates declined during a period of rapid scale‐up of ART. Nevertheless, both HIV‐positive and HIV‐negative TB notification rates remained very high. Decreases among HIV positives were likely blunted by TB remaining a major entry to the ART programme and occurring after delayed ART initiation. [ABSTRACT FROM AUTHOR]
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- 2015
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26. A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment.
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Johnson, Leigh F, Dorrington, Rob E, Laubscher, Ria, Hoffmann, Christopher J, Wood, Robin, Fox, Matthew P, Cornell, Morna, Schomaker, Michael, Prozesky, Hans, Tanser, Frank, Davies, Mary‐Ann, and Boulle, Andrew
- Abstract
Introduction: There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Methods: Completeness of death recording was estimated using a capture–recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. Results: After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3–94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2–35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004–2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). Conclusions: South Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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27. A comparison of linkage to HIV care after provider-initiated HIV testing and counselling (PITC) versus voluntary HIV counselling and testing (VCT) for patients with sexually transmitted infections in Cape Town, South Africa.
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Leon, Natalie, Mathews, Catherine, Lewin, Simon, Osler, Meg, Boulle, Andrew, and Lombard, Carl
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AIDS ,VOLUNTARY health agencies ,SEXUALLY transmitted diseases ,INTERVENTION (Social services) ,MEDICAL screening - Abstract
Background: We examined linkage to care for patients with sexually transmitted infection who were diagnosed HIVpositive via the provider-initiated HIV testing and counselling (PITC) approach, as compared to the voluntary counselling and testing (VCT) approach, as little is known about the impact of expanded testing strategies on linkage to care. Methods: In a controlled trial on PITC (Cape Town, 2007), we compared HIV follow-up care for a nested cohort of 930 HIV-positive patients. We cross-referenced HIV testing and laboratory records to determine access to CD4 and viral load testing as primary outcomes. Secondary outcomes were HIV immune status and time taken to be linked to HIV care. Logistic regression was performed to analyse the difference between arms. Results: There was no difference in the main outcomes of patients with a record of CD4 testing (69.9% in the intervention, 65.2% in control sites, OR 0.82 (CI: 0.44-1.51; p = 0.526) and viral load testing (14.9% intervention versus 10.9% control arm; OR 0.69 (CI: 0.42-1.12; p = 0.131). In the intervention arm, ART-eligible patients (based on low CD4 test result), accessed viral load testing approximately 2.5 months sooner than those in the control arm (214 days vs. 288 days, HR: 0.417, 95% CI: 0.221-0.784; p = 0.007). Conclusion: The PITC intervention did not improve linkage to CD4 testing, but shortened the time to viral load testing for ART-eligible patients. Major gaps found in follow-up care across both arms, indicate the need for more effective linkage-to-HIV care strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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28. Associations With Virologic Treatment Failure in Adults on Antiretroviral Therapy in South Africa.
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Datay, Mohammed Ishaaq, Boulle, Andrew, Mant, David, and Yudkin, Patricia
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CASE-control method , *HIGHLY active antiretroviral therapy , *MEDICAL virology , *CD4 antigen , *HEALTH outcome assessment - Abstract
The article presents a case-control study that examines the factors related to failures of virologic treatment in highly active antiretroviral therapy (HAART) settings. The study categorized visit-level data like treatment interruptions, demographic and social, and health status of patients and correlate such data on their HAART outcomes. Result shows that nevirapine-based prevention of mother-to-child transmission (PMTCT) and low CD4 count are related with virologic treatment failure.
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- 2010
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29. Initiation of highly active antiretroviral therapy among pregnant women in Cape Town, South Africa.
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Stinson, Kathryn, Boulle, Andrew, Coetzee, David, Abrams, Elaine J., and Myer, Landon
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HIGHLY active antiretroviral therapy , *PREGNANT women , *PRENATAL diagnosis , *GESTATIONAL age , *HIV-positive women - Abstract
Objective To investigate highly active antiretroviral therapy (HAART) initiation among pregnant women and the optimum model of service delivery for integrating HAART services into antenatal care. Methods We analysed clinic records to reconstruct a cohort of all HIV-infected pregnant women eligible for HAART at four antenatal clinics representing three service delivery models in Cape Town, South Africa. To assess HAART coverage, records of women determined to be eligible for HAART in pregnancy were reviewed at corresponding HIV treatment services. Results Of 13 208 pregnant women tested for HIV, 26% were HIV-infected and 15% were HAART-eligible based on a CD4 cell count of ≤ 200 cells/μl. Among eligible women, 51% initiated HAART before delivery, 27% received another prevention of mother-to-child transmission (PMTCT) intervention and 22% did not receive any antiretroviral intervention before delivery. The proportions of women initiating HAART between the different service delivery models were comparable. The median gestational age at first presentation was 26 weeks, and early gestational age at first presentation was the strongest predictor of being on HAART by delivery. Of the women who did not initiate HAART in pregnancy, 24% started treatment within 2 years postpartum. Conclusions In this setting with clear PMTCT and HAART protocols, services failed to prioritize and initiate a high proportion of eligible pregnant women on HAART. The initiation of HAART in pregnancy requires strengthened antenatal and HIV services that target women with advanced stage disease. [ABSTRACT FROM AUTHOR]
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- 2010
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30. Orphans of the AIDS epidemic? The extent, nature and circumstances of child-headed households in South Africa.
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Meintjes, Helen, Hall, Katharine, Marera, Double-Hugh, and Boulle, Andrew
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CHILDREN ,AIDS in adolescence ,AIDS in children ,HIV infection risk factors - Abstract
There is widespread concern that the number of children living in “child-headed households” is rapidly increasing as a result of AIDS-related adult mortality in much of sub-Saharan Africa. Based on analyses of data from several representative national surveys over the period 2000-2007, this paper examines the extent to which this is the case in South Africa. It explores trends in the number of children living in child-only households and characterises these children relative to children living in households with adults (mixed-generation households). The findings indicate that the proportion of child-only households is relatively small (0.47% in 2006) and does not appear to be increasing. In addition, the vast majority (92.1%) of children resident in child-only households have a living parent. The findings raise critical questions about the circumstances leading to the formation of child-only households and highlight that they cannot for the main part be ascribed to HIV orphaning. Nonetheless, the number of children living in this household form is not insignificant, and their circumstances, when compared with children in mixed-generation households, indicate a range of challenges, including greater economic vulnerability and inadequate service access. We argue that a solitary focus on the HIV epidemic and its related orphaning as the cause of child-only households masks other important issues for consideration in addressing their needs, and risks the development of inappropriate policies, programmes and interventions. [ABSTRACT FROM AUTHOR]
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- 2010
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31. A longitudinal analysis of the completeness of maternal HIV testing, including repeat testing in Cape Town, South Africa.
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Beer, Shani, Kalk, Emma, Kroon, Max, Boulle, Andrew, Osler, Meg, Euvrard, Jonathan, Timmerman, Venessa, and Davies, Mary‐Ann
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HIV ,HIV infection transmission ,HEALTH facilities ,PRENATAL care - Abstract
Introduction: The virtual elimination of mother‐to‐child transmission of HIV cannot be achieved without complete maternal HIV testing. The World Health Organization recommends that women in high HIV prevalent settings repeat HIV testing in the third trimester, and at delivery or directly thereafter. The Western Cape Province (South Africa) prevention of mother‐to‐child transmission (PMTCT) guidelines recommend a repeat maternal HIV test between 32 and 34 weeks gestation and at delivery in addition to testing at the first antenatal visit (ideally <20 weeks gestation). There are few published longitudinal studies on the uptake of initial and repeated maternal HIV testing programmes in sub‐Saharan Africa. We aimed to investigate the implementation of initial and repeat maternal HIV testing guidelines in Cape Town, South Africa. Methods: Between 2013 and 2016 we established an electronic PMTCT register that consolidated routine data from a primary healthcare facility and its secondary and tertiary referral sites in Cape Town. This provided a longitudinal record for each participant, from first antenatal visit to delivery. Utilizing these data, we conducted a retrospective analysis investigating the completeness of maternal HIV testing according to the PMTCT HIV testing guidelines in Cape Town, and predictors of complete testing, from 2014 to 2016. Results: Among 8558 enrolled pregnant women, 7213 (84%) were not known to be HIV positive at their first visit and thus eligible for HIV testing; 91% of them received ≥1 HIV test during pregnancy/delivery. Testing at the first visit was 98% among the 85% of women who attended antenatal care. Among women eligible to receive all three recommended HIV tests, only 11% achieved all three tests. Delivery HIV testing completion among all women without an HIV‐positive diagnosis was 23%. HIV prevalence at delivery was 21% and HIV incidence between first visit and delivery in those with ≥2 HIV tests was 0.2%. Women who enrolled after 2014 were more likely to receive the three recommended tests (aOR: 1.41; 95% CI: 1.10 to 1.81) and retest at delivery (aOR: 1.20; 95% CI: 1.05 to 1.39). Conclusions: Implementation of maternal HIV testing in Cape Town improved between 2014 and 2016 but major gaps remain, particularly at delivery. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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32. Effectiveness of the first district-wide programme for the prevention of mother-to-child transmission of HIV in South Africa.
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Coetzee, David, Hilderbrand, Katherine, Boulle, Andrew, Draper, Beverley, Abdullah, Fareed, and Goemaere, Eric
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PREVENTIVE medicine , *HIV , *DNA polymerases , *POLYMERASE chain reaction , *AZIDOTHYMIDINE , *PREGNANCY , *INFANT nutrition , *MEDICAL sciences - Abstract
Objective The aim of this study was to estimate the field efficacy of the first routine programme for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) initiated in South Africa, in the subdistrict of Khayelitsha. Methods A consecutive sample of 658 mother-infant pairs, identified from the PMTCT register from 1 March to 30 November 2003, were identified for enrolment in this study. Details of the regimen received were established and HIV status of the infants at between 6 and 10 weeks of age was determined by qualitative DNA polymerase chain reaction. Zidovudine (AZT) was provided ante-natally from week 34 of gestation and during labour. Infant formula milk was offered to mothers who chose not to breastfeed. The protocol was amended in July 2003 such that women who had received < 2 weeks of treatment with AZT were given a single dose of nevirapine (NVP) at the onset of labour, and the infant received a weight-adjusted dose of NVP within 72 h of delivery. Results Of the 535 mother-infant pairs (81%) eventually included in the study, 410 (77%) received an effective PMTCT intervention according to the protocol. The rate of transmission of HIV from mother to child was 8.8% (95% confidence interval (CI), 6.2-10.9). A maternal age of > 25 years was the only significant independent risk factor for transmission (odds ratio, 2.12; 95% CI, 1.14-4.07). Conclusion The results of this study demonstrate the feasibility and effectiveness of a large-scale PMTCT programme in an urban public-sector setting. [ABSTRACT FROM AUTHOR]
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- 2007
33. Effectiveness of the first district-wide programme for the prevention of mother-to-child transmission of HIV in South Africa.
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Coetzee, David, Hilderbrand, Katherine, Boulle, Andrew, Draper, Beverley, Abdullah, Fareed, and Goemaere, Eric
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PREVENTION of communicable diseases , *VIRUS disease transmission , *HIV infections , *LENTIVIRUS diseases , *INFECTIOUS disease transmission , *WORLD health , *PUBLIC health - Abstract
Objective The aim of this study was to estimate the field efficacy of the first routine programme for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) initiated in South Africa, in the subdistrict of Khayelitsha. Methods A consecutive sample of 658 mother-infant pairs, identified from the PMTCT register from 1 March to 30 November 2003, were identified for enrolment in this study. Details of the regimen received were established and HIV status of the infants at between 6 and 10 weeks of age was determined by qualitative DNA polymerase chain reaction. Zidovudine (AZT) was provided antenatally from week 34 of gestation and during labour. Infant formula milk was offered to mothers who chose not to breastfeed. The protocol was amended in July 2003 such that women who had received < 2 weeks of treatment with AZT were given a single dose of nevirapine (NVP) at the onset of labour, and the infant received a weight-adjusted dose of NVP within 72 h of delivery. Results Of the 535 mother-infant pairs (81%) eventually included in the study, 410 (77%) received an effective PMTCT intervention according to the protocol. The rate of transmission of HIV from mother to child was 8.8% (95% confidence interval (CI), 6.2–10.9). A maternal age of > 25 years was the only significant independent risk factor for transmission (odds ratio, 2.12; 95% CI, 1.14–4.07). Conclusion The results of this study demonstrate the feasibility and effectiveness of a large-scale PMTCT programme in an urban public-sector setting. [ABSTRACT FROM AUTHOR]
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- 2005
34. Loss to follow-up from antiretroviral therapy clinics: A systematic review and meta-analysis of published studies in South Africa from 2011 to 2015.
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Kaplan, Samantha, Nteso, Katleho S., Ford, Nathan, Boulle, Andrew, and Meintjes, Graeme
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META-analysis , *ANTIRETROVIRAL agents , *DEFINITIONS , *CLINICS , *SOUTH Africans - Abstract
Background: South Africa has the largest antiretroviral therapy (ART) programme in the world. To optimise programme outcomes, it is critical that patients are retained in care and that retention is accurately measured. Objectives: To identify all studies published in South Africa from 2011 to 2015 that used loss to follow-up (LTFU) as an indicator or outcome to describe the variation in definitions and to estimate the proportion of patients lost to care across studies. Method: All studies published between 01 January 2011 and October 2015 that included loss to follow-up or default from ART care in a South African cohort were included by use of a broad search strategy across multiple databases. To be included, the cohort had to include any patient ART data, including follow-up time, from 01 January 2010. Two authors, working independently, extracted data and assessed risk of bias from all manuscripts. Meta-analysis was performed for studies stratified by the same loss to follow-up definition. Results: Forty-eight adult, 15 paediatric and 4 pregnant cohorts were included. Median cohort size was 3737; follow-up time ranged from 9 weeks to 5 years. Meta-analysis did not reveal an important difference in LTFU estimates in adult cohorts at 1 year between loss to follow-up defined as 3 months (11.0%, n = 4; 95% CI 10.7% – 11.2%) compared with 6 months (12.0%, n = 4; 95% CI 11.8% – 12.2%). Only two cohorts reported reliable LTFU estimates at 5 years: this was 25.1% (95% CI 24.8% – 25.4%). Conclusion: South Africa should standardise a LTFU definition. This would aid in monitoring and evaluation of ART programmes, with the broader goal of improving patient outcomes. [ABSTRACT FROM AUTHOR]
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- 2019
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35. Assessing the Association Between Changing NRTIs When Initiating Second-Line ART and Treatment Outcomes.
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Rohr, Julia K., Ive, Prudence, Horsburgh, Charles Robert, Berhanu, Rebecca, Hoffmann, Christopher J., Wood, Robin, Boulle, Andrew, Giddy, Janet, Prozesky, Hans, Vinikoor, Michael, Mwanza, Mwanzawa, Wandeler, Gilles, Davies, Mary-Ann, and Fox, Matthew P.
- Abstract
Background: After first-line antiretroviral therapy failure, the importance of change in nucleoside reverse transcriptase inhibitor (NRTI) in second line is uncertain due to the high potency of protease inhibitors used in second line. Setting : We used clinical data from 6290 adult patients in South Africa and Zambia from the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Southern Africa cohort. Methods: We included patients who initiated on standard first-line antiretroviral therapy and had evidence of first-line failure. We used propensity score-adjusted Cox proportional-hazards models to evaluate the impact of change in NRTI on second-line failure compared with remaining on the same NRTI in second line. In South Africa, where viral load monitoring was available, treatment failure was defined as 2 consecutive viral loads >1000 copies/mL. In Zambia, it was defined as 2 consecutive CD4 counts <100 cells/mm³. Results: Among patients in South Africa initiated on zidovudine (AZT), the adjusted hazard ratio for second-line virologic failure was 0.25 (95% confidence interval: 0.11 to 0.57) for those switching to tenofovir (TDF) vs. remaining on AZT. Among patients in South Africa initiated on TDF, switching to AZT in second line was associated with reduced second-line failure (adjusted hazard ratio = 0.35 [95% confidence interval: 0.13 to 0.96]). In Zambia, where viral load monitoring was not available, results were less conclusive. Conclusions: Changing NRTI in second line was associated with better clinical outcomes in South Africa. Additional clinical trial research regarding second-line NRTI choices for patients initiated on TDF or with contraindications to specific NRTIs is needed. [ABSTRACT FROM AUTHOR]
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- 2018
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36. Evaluation of a Public-Sector, Provider-Initiated Cryptococcal Antigen Screening and Treatment Program, Western Cape, South Africa.
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Vallabhaneni, Snigdha, Longley, Nicky, Smith, Mariette, Smith, Rachel, Osler, Meg, Kelly, Nicola, Cross, Anna, Boulle, Andrew, Meintjes, Graeme, and Govender, Nelesh P.
- Abstract
Background: Screening for serum cryptococcal antigen (CrAg) may identify those at risk for disseminated cryptococcal disease (DCD), and preemptive fluconazole treatment may prevent progression to DCD. In August 2012, the Western Cape Province (WC), South Africa, adopted provider-initiated CrAg screening. We evaluated the implementation and effectiveness of this large-scale public-sector program during its first year, September 1, 2012-August 31, 2013. Methods: We used data from the South African National Health Laboratory Service, WC provincial HIV program, and nationwide surveillance data for DCD. We assessed the proportion of eligible patients screened for CrAg (CrAg test done within 30 days of CD4 date) and the prevalence of CrAg positivity. Incidence of DCD among those screened was compared with those not screened. Results: Of 4395 eligible patients, 26.6% (n = 1170) were screened. The proportion of patients screened increased from 15.9% in September 2012 to 36.6% in August 2013. The prevalence of positive serum CrAg was 2.1%. Treatment data were available for 13 of 24 CrAg-positive patients; 9 of 13 were treated with fluconazole. Nine (0.8%) incident cases of DCD occurred among the 1170 patients who were screened for CrAg vs. 49 (1.5%) incident cases among the 3225 patients not screened (P = 0.07). Conclusions: Relatively few eligible patients were screened under the WC provider-initiated CrAg screening program. Unscreened patients were nearly twice as likely to develop DCD. CrAg screening can reduce the burden of DCD, but needs to be implemented well. To improve screening rates, countries should consider laboratory-based reflexive screening when possible. [ABSTRACT FROM AUTHOR]
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- 2016
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37. Reduced amplification efficiency of the RNA-dependent-RNA-polymerase target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests.
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Valley-Omar, Ziyaad, Marais, Gert, Iranzadeh, Arash, Naidoo, Michelle, Korsman, Stephen, Maponga, Tongai, Hussey, Hannah, Davies, Mary-Ann, Boulle, Andrew, Doolabh, Deelan, Laubscher, Mariska, Wojno, Justyna, Deetlefs, J.D., Maritz, Jean, Scott, Lesley, Msomi, Nokukhanya, Naicker, Cherise, Tegally, Houriiyah, de Oliveira, Tulio, and Bhiman, Jinal
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SARS-CoV-2 Delta variant , *EXOMES , *ROUTINE diagnostic tests , *SARS-CoV-2 , *WHOLE genome sequencing , *GENE targeting , *REVERSE transcriptase - Abstract
• SARS-CoV-2 Gene Target Failure for Delta variants. • Detection of SARS CoV-2 Delta variant without genomic sequencing. • Emergence of SARS-CoV-2 variant in South Africa. • SARS-CoV-2 variant dynamics in South Africa. Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (RΔE) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median RΔE for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring RΔE value can serve as a useful surrogate for rapid tracking of Delta variant prevalence. [ABSTRACT FROM AUTHOR]
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- 2022
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38. Convergence of Mortality Rates among Patients on Antiretroviral Therapy in South Africa and North America
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Susana Monge, Jodie L. Guest, M. John Gill, Daniela Garone, James Ndirangu, Kathrin Ehren, Colin Campbell, Robert S. Hogg, Matthew P. Fox, Olivia Keiser, Jonathan A C Sterne, Heidi M. Crane, Amy C. Justice, Michael S. Saag, Antonella Castagna, Dominique Costagliola, Michael Schomaker, Janet Giddy, Suzanne M Ingle, Fiona C Lampe, Andrew Boulle, Peter Reiss, Bryan E. Shepherd, François Dabis, Margaret T May, Matthias Egger, Boulle, Andrew, Schomaker, Michael, May, Margaret T., Hogg, Robert S., Shepherd, Bryan E., Monge, Susana, Keiser, Olivia, Lampe, Fiona C., Giddy, Janet, Ndirangu, Jame, Garone, Daniela, Fox, Matthew, Ingle, Suzanne M., Reiss, Peter, Dabis, Francoi, Costagliola, Dominique, Castagna, Antonella, Ehren, Kathrin, Campbell, Colin, Gill, M. John, Saag, Michael, Justice, Amy C., Guest, Jodie, Crane, Heidi M., Egger, Matthia, Sterne, Jonathan A. C., Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, Department of Public Health and Family Medicine, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, and Global Health
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Male ,Viral Diseases ,Epidemiology ,lcsh:Medicine ,HIV Infections ,Plant Science ,Global Health ,Biochemistry ,Cohort Studies ,South Africa ,Antiretroviral Therapy, Highly Active ,Case fatality rate ,Medicine and Health Sciences ,Medicine ,Public and Occupational Health ,Viral load ,HIV Infection ,Prospective Studies ,Cooperative Behavior ,education.field_of_study ,Death rates ,Mortality rate ,General Medicine ,Middle Aged ,Antiretroviral therapy ,3. Good health ,AIDS ,Europe ,Infectious Diseases ,Cohort ,Female ,Developed country ,Research Article ,Human ,Biotechnology ,Cohort study ,Adult ,Anti-HIV Agents ,Population ,Sexually Transmitted Diseases ,Developing country ,610 Medicine & health ,Infectious Disease Epidemiology ,Follow-Up Studie ,Acquired immunodeficiency syndrome (AIDS) ,360 Social problems & social services ,parasitic diseases ,Humans ,Mortality ,education ,Molecular Biology ,business.industry ,lcsh:R ,Biology and Life Sciences ,HIV ,Anti-HIV Agent ,Cell Biology ,Plant Pathology ,medicine.disease ,Social Epidemiology ,Prospective Studie ,North America ,HIV-1 ,Cohort Studie ,business ,Follow-Up Studies ,Demography - Abstract
Analyzing survival in HIV treatment cohorts, Andrew Boulle and colleagues find mortality rates in South Africa comparable to or better than those in North America by 4 years after starting antiretroviral therapy. Please see later in the article for the Editors' Summary, Background High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count, Editors' Summary Background AIDS has killed about 36 million people since the first recorded case of the disease in 1981, and a similar number of people (including 25 million living in sub-Saharan Africa) are currently infected with HIV, the virus that causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other serious infections. Early in the AIDS epidemic, HIV-positive people usually died within 10 years of becoming infected. In 1996, effective antiretroviral therapy (ART) became available and, for people living in high-income countries, HIV infection became a chronic condition. But ART was expensive, so HIV/AIDS remained largely untreated and fatal in resource-limited countries. Then, in 2003, the international community began to work towards achieving universal access to ART. By the end of 2012, nearly two-thirds of HIV-positive people (nearly 10 million individuals) living in low- and middle-income countries who were eligible for treatment because their CD4 cell count had fallen below 350/mm3 blood or because they had developed an AIDS-defining condition were receiving treatment. Why Was This Study Done? It is known that a larger proportion of HIV-positive patients starting ART die during the first year of treatment in sub-Saharan Africa than in Europe and North America. This difference arises in part because patients in resource-limited settings tend to have lower CD4 counts when they start treatment than patients in wealthy countries. However, the lack of reliable data on mortality (death) in resource-limited settings has made it hard to compare longer-term outcomes in different settings. Information on the long-term outcomes of HIV-positive patients receiving ART in resource-limited countries is needed to guide the development of appropriate health systems and treatment regimens in these settings. In this collaborative analysis of prospective cohort studies, the researchers compare mortality up to 4 years on ART in South Africa, Europe, and North America. A prospective cohort study follows a group of individuals over time to see whether differences in specific characteristics at the start of the study affect subsequent outcomes. A collaborative analysis combines individual patient data from several studies. What Did the Researchers Do and Find? The researchers combined data from four South Africa cohorts of HIV-positive patients starting ART included in the International Epidemiologic Databases to Evaluate AIDS South African (IeDEA-SA) collaboration with data from six North American cohorts and nine European cohorts included in the ART Cohort Collaboration (ART-CC). The South African cohorts were chosen because unusually for studies undertaken in countries in sub-Saharan Africa the vital status of patients (whether they had died) who had been lost to follow-up in these cohorts could be obtained from the national population register. Patients in South Africa began treatment with more advanced disease (indicated by a lower average CD4 count) than patients in Europe or North America. Notably, high early mortality after starting ART in South Africa occurred mainly in patients starting ART with a CD4 count below 50 cells/mm3. The cumulative mortality after 4 years of ART was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. After adjusting for patient characteristics at ART initiation, the mortality rate among patients beginning ART was initially lower in Europe and North American than in South Africa. However, although the adjusted mortality rate in Europe remained lower than the rate in South Africa, the rate in North America was higher than that in South Africa between 24 and 48 months on ART. What Do These Findings Mean? Although the linkage to national vital registration systems (databases of births and deaths) undertaken in this collaborative analysis is likely to have greatly reduced bias due to under-ascertainment of mortality, the accuracy of these findings may still be limited by differences in how this linkage was undertaken in different settings. Nevertheless, these findings suggest that mortality among HIV-infected patients receiving ART in South Africa, although initially higher than in Europe and North America, rapidly declines with increasing duration on ART and, after 4 years of treatment, approaches the rate seen in high-income settings. Intriguingly, these findings also highlight the relatively higher late mortality in North America compared to either Europe or South Africa, a result that needs to be investigated to explore the extent to which differences in mortality ascertainment, patient characteristics and comorbidities, or health systems and treatment regimens contribute to variations in outcomes among HIV-positive patients in various settings. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001718. This study is further discussed in a PLOS Medicine Perspective by Agnes Binagwaho and colleagues Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on universal access to ART, on HIV and AIDS in sub-Saharan Africa, and on HIV and AIDS in South Africa (in English and Spanish) The World Health Organization provides information on all aspects of HIV/AIDS (in several languages); its 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infections: recommendations for a public health approach are available The 2013 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it Information about the International Epidemiologic Databases to Evaluate AIDS South African (IeDEA-SA) collaboration and about the ART Cohort Collaboration is available Personal stories about living with HIV/AIDS are available through Avert, Nam/aidsmap, and Healthtalkonline
- Published
- 2014
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