Browsing by Author "Fatti, Geoffrey"

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Characteristics and outcomes of adolescents living with perinatally acquired HIV within Southern Africa.
(2020-Dec-01) Tsondai, Priscilla R.; Braithwaite, Kate; Fatti, Geoffrey; Bolton-Moore, Carolyn; Chimbetete, Cleophas ; Rabie, Helena; Phiri, Sam; Sawry, Shobna ; Eley, Brian; Hobbins, Michael A.; Boulle, Andrew; Taghavi, Katayoun; Sohn, Annette H.; Davies, Mary-Ann
BACKGROUND: Using data from 15 International epidemiology Databases to Evaluate AIDS in Southern Africa sites, we compared the characteristics and outcomes of adolescents living with perinatally acquired HIV (ALPH). METHODS: We included ALPH entering care aged less than 13 years with at least one HIV care visit during adolescence (10-19 years). We compared the characteristics and cross-sectional outcomes: transfer out, loss to follow-up (no visit in the 12 months prior to database closure), mortality, and retention between those who entered care aged less than 10 vs. aged 10-13 years; and explored predictors of mortality after age 13 years using Cox Proportional Hazards models. RESULTS: Overall, 16 229 (50% female) ALPH who entered HIV care aged less than 10 years and 8897 (54% female) aged 10-13 years were included and followed for 152 574 person-years. During follow-up, 94.1% initiated antiretroviral therapy, with those who entered care aged less than 10 more likely to have initiated antiretroviral therapy [97.9%, 95% confidence interval (CI) 97.6; 98.1%] than those who presented aged 10-13 years (87.3%, 95% CI 86.6; 88.0%). At the end of follow-up, 3% had died (entered care aged <10 vs. 10-13 years; 1.4 vs. 5.1%), 22% were loss to follow-up (16.2 vs. 33.4%), and 59% (66.4 vs. 45.4%) were retained. There was no difference in the risk of dying after the age of 13 years between adolescents entering care aged less than 10 vs. 10-13 years (adjusted hazard ratio 0.72; 95% CI 0.36; 1.42). CONCLUSION: Retention outcomes for ALPH progressively worsened with increasing age, with these outcomes substantially worse among adolescents entering HIV care aged 10-13 vs. less than 10 years.
Characterizing the double-sided cascade of care for adolescents living with HIV transitioning to adulthood across Southern Africa.
(2020-Jan) Tsondai, Priscilla R.; Sohn, Annette H.; Phiri, Sam; Sikombe, Kombatende; Sawry, Shobna ; Chimbetete, Cleophas; Fatti, Geoffrey; Hobbins, Michael A.; Technau, Karl-Günter ; Rabie, Helena; Bernheimer, Jonathan; Fox, Matthew P.; Judd, Ali; Collins, Intira J.; Davies, Mary-Ann
INTRODUCTION: As adolescents and young people living with HIV (AYLH) age, they face a "transition cascade," a series of steps associated with transitions in their care as they become responsible for their own healthcare. In high-income countries, this usually includes transfer from predominantly paediatric/adolescent to adult clinics. In sub-Saharan Africa, paediatric HIV care is mostly provided in decentralized, non-specialist primary care clinics, where "transition" may not necessarily include transfer of care but entails becoming more autonomous for one's HIV care. Using different age thresholds as proxies for when "transition" to autonomy might occur, we evaluated pre- and post-transition outcomes among AYLH. METHODS: We included AYLH aged <16 years at enrolment, receiving antiretroviral therapy (ART) within International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) sites (2004 to 2017) with no history of transferring care. Using the ages of 16, 18, 20 and 22 years as proxies for "transition to autonomy," we compared the outcomes: no gap in care (≥2 clinic visits) and viral suppression (HIV-RNA <400 copies/mL) in the 12 months before and after each age threshold. Using log-binomial regression, we examined factors associated with no gap in care (retention) in the 12 months post-transition. RESULTS: A total of 5516 AYLH from 16 sites were included at "transition" age 16 (transition-16y), 3864 at 18 (transition-18y), 1463 at 20 (transition-20y) and 440 at 22 years (transition-22y). At transition-18y, in the 12 months pre- and post-transition, 83% versus 74% of AYLH had no gap in care (difference 9.3 (95% confidence interval (CI) 7.8 to 10.9)); while 65% versus 62% were virally suppressed (difference 2.7 (-1.0 to 6.5%)). The strongest predictor of being retained post-transition was having no gap in the preceding year, across all transition age thresholds (transition-16y: adjusted risk ratio (aRR) 1.72; 95% CI (1.60 to 1.86); transition-18y: aRR 1.76 (1.61 to 1.92); transition-20y: aRR 1.75 (1.53 to 2.01); transition-22y: aRR 1.47; (1.21 to 1.78)). CONCLUSIONS: AYLH with gaps in care need targeted support to prevent non-retention as they take on greater responsibility for their healthcare. Interventions to increase virologic suppression rates are necessary for all AYLH ageing to adulthood.
Implementation and Operational Research: Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings.
(2015-Nov-01) Koller, Manuel; Fatti, Geoffrey; Chi, Benjamin H.; Keiser, Olivia; Hoffmann, Christopher J.; Wood, Robin; Prozesky, Hans; Stinson, Kathryn; Giddy, Janet; Mutevedzi, Portia; Fox, Matthew P.; Law, Matthew; Boulle, Andrew; Egger, Matthias
BACKGROUND: HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS: We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20%, or 40% of patients in 7 cohorts of patients starting ART in South Africa, and plotted cutoffs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia, and the Asia-Pacific. RESULTS: In total, 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African cohort, from 64% to 93% in the Zambian cohort, and from 73% to 96% in the Asia-Pacific cohort. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia, and from 37% to 71% in Asia-Pacific. The area under the receiver operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia, and from 0.77 to 0.92 in Asia-Pacific. CONCLUSIONS: CD4-based risk charts with optimal cutoffs for targeted VL testing maybe useful to monitor ART in settings where VL capacity is limited.
Medication Side Effects and Retention in HIV Treatment: A Regression Discontinuity Study of Tenofovir Implementation in South Africa and Zambia.
(2018-Sep-01) Brennan, Alana T.; Bor, Jacob; Davies, Mary-Ann; Wandeler, Gilles; Prozesky, Hans; Fatti, Geoffrey; Wood, Robin; Stinson, Kathryn; Tanser, Frank; Bärnighausen, Till; Boulle, Andrew; Sikazwe, Izukanji; Zanolini, Arianna; Fox, Matthew P.
Tenofovir is less toxic than other nucleoside reverse-transcriptase inhibitors used in antiretroviral therapy (ART) and may improve retention of human immunodeficiency virus (HIV)-infected patients on ART. We assessed the impact of national guideline changes in South Africa (2010) and Zambia (2007) recommending tenofovir for first-line ART. We applied regression discontinuity in a prospective cohort study of 52,294 HIV-infected adults initiating first-line ART within 12 months (±12 months) of each guideline change. We compared outcomes in patients presenting just before and after the guideline changes using local linear regression and estimated intention-to-treat effects on initiation of tenofovir, retention in care, and other treatment outcomes at 24 months. We assessed complier causal effects among patients starting tenofovir. The new guidelines increased the percentages of patients initiating tenofovir in South Africa (risk difference (RD) = 81 percentage points, 95% confidence interval (CI): 73, 89) and Zambia (RD = 42 percentage points, 95% CI: 38, 45). With the guideline change, the percentage of single-drug substitutions decreased substantially in South Africa (RD = -15 percentage points, 95% CI: -18, -12). Starting tenofovir also reduced attrition in Zambia (intent-to-treat RD = -1.8% (95% CI: -3.5, -0.1); complier relative risk = 0.74) but not in South Africa (RD = -0.9% (95% CI: -5.9, 4.1); complier relative risk = 0.94). These results highlight the importance of reducing side effects for increasing retention in care, as well as the differences in population impact of policies with heterogeneous treatment effects implemented in different contexts.
Temporal Trends in Co-trimoxazole Use Among Children on Antiretroviral Therapy and the Impact of Co-trimoxazole on Mortality Rates in Children Without Severe Immunodeficiency.
(2019-Nov-06) Boettiger, David C.; Law, Matthew G.; Sohn, Annette H.; Davies, Mary-Ann; Wools-Kaloustian, Kara; Leroy, Valeriane; Yotebieng, Marcel; Vinikoor, Michael J.; Vreeman, Rachel; Amorissani-Folquet, Madeleine; Edmonds, Andrew; Fatti, Geoffrey; Batte, James; Renner, Lorna; Adedimeji, Adebola ; Kariminia, Azar
BACKGROUND: Co-trimoxazole is recommended for all children with human immunodeficiency virus. In this analysis, we evaluate trends in pediatric co-trimoxazole use and survival on co-trimoxazole in children using antiretroviral therapy (ART). METHODS: We used data collected between January 1, 2006, and March 31, 2016, from the International Epidemiology Databases to Evaluate AIDS. Logistic regression was used to evaluate factors associated with using co-trimoxazole at ART initiation. Competing risk regression was used to assess factors associated with death. RESULTS: A total of 54113 children were included in this study. The prevalence of co-trimoxazole use at ART initiation increased from 66.5% in 2006 to a peak of 85.6% in 2010 and then declined to 48.5% in 2015-2016. A similar trend was observed among children who started ART with severe immunodeficiency. After adjusting for year of ART initiation, younger age (odds ratio [OR], 1.18 for <1 vs 1 to <5 years of age [95% confidence interval (CI), 1.09-1.28]), lower height-for-age z score (OR, 1.15 for less than -3 vs greater than -2 [95% CI, 1.08-1.22]), anemia (OR, 1.08 [95% CI, 1.02-1.15]), severe immunodeficiency (OR, 1.25 [95% CI, 1.18-1.32]), and receiving care in East Africa (OR, 8.97 vs Southern Africa [95% CI, 8.17-9.85]) were associated with a high prevalence of co-trimoxazole use. Survival did not differ according to co-trimoxazole use in children without severe immunodeficiency (hazard ratio, 1.01 for nonusers versus users [95% CI, 0.77-1.34]). CONCLUSIONS: Recent declines in co-trimoxazole use may not be linked to the current shift toward early ART initiation. Randomized trial data might be needed to establish the survival benefit of co-trimoxazole in children without severe immunodeficiency.
Trends in CD4 and viral load testing 2005 to 2018: multi-cohort study of people living with HIV in Southern Africa.
(2020-Jul) Zaniewski, Elizabeth; Ostinelli, Cam H. D.; Chammartin, Frédérique; Maxwell, Nicola; Davies, Mary-Ann; Euvrard, Jonathan; van Dijk, Janneke; Bosomprah, Samuel; Phiri, Sam; Tanser, Frank; Sipambo, Nosisa; Muhairwe, Josephine ; Fatti, Geoffrey; Prozesky, Hans; Wood, Robin; Ford, Nathan; Fox, Matthew P.; Egger, Matthias
INTRODUCTION: The World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa. METHODS: We analysed data from 14 HIV treatment programmes in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in 2005 to 2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count <200 cells/mm RESULTS: Among 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017; the probability declined by 14% each year (odds ratio (OR) 0.86; 95% CI 0.86 to 0.86). Frequency of CD4 testing also declined. The percentage starting ART with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018; each year the probability declined by 20% (OR 0.80; 95% CI 0.80 to 0.81). VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested, but fewer than 2% were tested in the other four countries. The probability of VL testing after ART start increased only modestly each year (OR 1.06; 95% CI 1.05 to 1.06). The percentage with unsuppressed VL was 8.6%. There was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99 to 1.01). CONCLUSIONS: CD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa.