Publications by authors named "Janet Giddy"

78 Publications

Changing contextual factors from baseline to 9-months post-HIV diagnosis predict 5-year mortality in Durban, South Africa.

AIDS Care 2020 Nov 2:1-8. Epub 2020 Nov 2.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.

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 , 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.
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http://dx.doi.org/10.1080/09540121.2020.1837338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088454PMC
November 2020

Identifying and predicting longitudinal trajectories of care for people newly diagnosed with HIV in South Africa.

PLoS One 2020 21;15(9):e0238975. Epub 2020 Sep 21.

Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

Background: Predicting long-term care trajectories at the time of HIV diagnosis may allow targeted interventions. Our objective was to uncover distinct CD4-based trajectories and determine baseline demographic, clinical, and contextual factors associated with trajectory membership.

Methods: We used data from the Sizanani trial (NCT01188941), in which adults were enrolled prior to HIV testing in Durban, South Africa from August 2010-January 2013. We ascertained CD4 counts from the National Health Laboratory Service over 5y follow-up. We used group-based statistical modeling to identify groups with similar CD4 count trajectories and Bayesian information criteria to determine distinct CD4 trajectories. We evaluated baseline factors that predict membership in specific trajectories using multinomial logistic regression. We examined calendar year of participant enrollment, age, gender, cohabitation, TB positivity, self-identified barriers to care, and ART initiation within 3 months of diagnosis.

Results: 688 participants had longitudinal data available. Group-based trajectory modeling identified four distinct trajectories: one with consistently low CD4 counts (21%), one with low CD4 counts that increased over time (22%), one with moderate CD4 counts that remained stable (41%), and one with high CD4 counts that increased over time (16%). Those with higher CD4 counts at diagnosis were younger, less likely to have TB, and less likely to identify barriers to care. Those in the least favorable trajectory (consistently low CD4 count) were least likely to start ART within 3 months.

Conclusions: One-fifth of people newly-diagnosed with HIV presented with low CD4 counts that failed to rise over time. Less than 40% were in a trajectory characterized by increasing CD4 counts. Patients in more favorable trajectories were younger, less likely to have TB, and less likely to report barriers to healthcare. Better understanding barriers to early care engagement and ART initiation will be necessary to improve long-term clinical outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238975PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505419PMC
October 2020

Virologic response to efavirenz-based first-line antiretroviral therapy in children with previous exposure to antiretrovirals to prevent mother-to-child transmission.

PLoS One 2020 29;15(5):e0233693. Epub 2020 May 29.

Wits Reproductive Health and HIV Institute (Wits RHI), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Efavirenz-based first-line regimens have been widely used for children ≥3 years of age starting antiretroviral therapy, despite possible resistance with prior exposure to non-nucleoside reverse transcriptase inhibitors for prevention of mother-to-child transmission (PMTCT). We used logistic regression to examine the association between PMTCT exposure and viral failure (VF) defined as two consecutive viral loads (VL)>1000 copies/ml between 6-18 months on ART. Children with previous nevirapine exposure for PMTCT were not at higher risk of VF compared to unexposed children (adjusted Odds Ratio (aOR): 0.79; 95% CI:0.56, 1.11).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233693PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259572PMC
August 2020

Assessing rates and contextual predictors of 5-year mortality among HIV-infected and HIV-uninfected individuals following HIV testing in Durban, South Africa.

BMC Infect Dis 2019 Aug 28;19(1):751. Epub 2019 Aug 28.

Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.

Background: Little is known about contextual factors that predict long-term mortality following HIV testing in resource-limited settings. We evaluated the impact of contextual factors on 5-year mortality among HIV-infected and HIV-uninfected individuals in Durban, South Africa.

Methods: We used data from the Sizanani trial (NCT01188941) in which adults (≥18y) were enrolled prior to HIV testing at 4 outpatient sites. We ascertained vital status via the South African National Population Register. We used random survival forests to identify the most influential predictors of time to death and incorporated these into a Cox model that included age, gender, HIV status, CD4 count, healthcare usage, health facility type, mental health, and self-identified barriers to care (i.e., service delivery, financial, logistical, structural and perceived health).

Results: Among 4816 participants, 39% were HIV-infected. Median age was 31y and 49% were female. 380 of 2508 with survival information (15%) died during median follow-up of 5.8y. For both HIV-infected and HIV-uninfected participants, each additional barrier domain increased the HR of dying by 11% (HR 1.11, 95% CI 1.05-1.18). Every 10-point increase in mental health score decreased the HR by 7% (HR 0.93, 95% CI 0.89-0.97). The hazard ratio (HR) for death of HIV-infected versus HIV-uninfected varied by age: HR of 6.59 (95% CI: 4.79-9.06) at age 20 dropping to a HR of 1.13 (95% CI: 0.86-1.48) at age 60.

Conclusions: Independent of serostatus, more self-identified barrier domains and poorer mental health increased mortality risk. Additionally, the impact of HIV on mortality was most pronounced in younger persons. These factors may be used to identify high-risk individuals requiring intensive follow up, regardless of serostatus.

Trial Registration: Clinical Trials.gov Identifier NCT01188941. Registered 26 August 2010.
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http://dx.doi.org/10.1186/s12879-019-4373-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712739PMC
August 2019

Using national laboratory data to assess cumulative frequency of linkage after transfer to community-based HIV clinics in South Africa.

J Int AIDS Soc 2019 06;22(6):e25326

Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Introduction: Changes to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) funding have led to closures of non-governmental HIV clinics with patient transfers to government-funded clinics. We sought to determine the success of transfers in South Africa using a national data source.

Methods: All adults (≥18 years) on antiretroviral therapy (ART) who visited a single PEPFAR-funded hospital-based HIV clinic in Durban, South Africa from March to June 2012 were transferred to community-based clinics. Previously, we matched patient records from the hospital-based HIV clinic with National Health Laboratory Services (NHLS) Corporate Data Warehouse (CDW) data to estimate the proportion of patients with a CD4 count or viral load (VL) in the CDW during the year before transfer. As a proxy for retention in care, in this study we evaluated whether patients had a CD4 count or VL at another facility within approximately three years of transfer. Patients referred to a private doctor at transfer were excluded from the analysis. We assessed predictors (age, sex, CD4 count, VL status, ART duration and location of future care) of not having post-transfer laboratory data using Cox proportional hazards models.

Results: Of the 3893 patients referred to a government facility at transfer, 41% were male and median age was 39 years (IQR 34 to 46). There was a post-transfer CD4 count or VL from another facility for 23% of these individuals within six months, 44% within one year, 57% within two years and 61% within approximately three years. Male sex (aHR 1.20, 95% CI 1.10 to 1.31) and shorter duration on ART (<3 months, aHR 3.80, 95% CI 2.77 to 5.21; three months to one year, aHR 1.32, 95% CI 1.15 to 1.51, each compared with >1 year) were associated with not having a post-transfer record.

Conclusions: Using data from the NHLS CDW, 61% of patients had evidence of a post-transfer laboratory record at another facility within approximately three years after closure of a large South African HIV clinic. Males and those with shorter time on ART prior to transfer were at highest risk for lacking follow-up laboratory data. As patients transfer care, national data sources can be used to evaluate long-term patient care trajectories.
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http://dx.doi.org/10.1002/jia2.25326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595194PMC
June 2019

Cervical cancer risk in women living with HIV across four continents: A multicohort study.

Int J Cancer 2020 02 19;146(3):601-609. Epub 2019 Jun 19.

Infectious and Tropical Diseases Institute, University of Brescia, Brescia, Italy.

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/μl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.
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http://dx.doi.org/10.1002/ijc.32260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898726PMC
February 2020

What Should We Do When HIV-positive Children Fail First-line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies.

Pediatr Infect Dis J 2019 04;38(4):400-405

Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa.

Background: Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence, and the development of HIV resistance mutations. We aimed to evaluate 4 management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes.

Methods: We included children (< 16 years of age) with VF from 8 International Epidemiologic Database to Evaluate AIDS Southern Africa cohorts, initiating combination antiretroviral therapy (cART) between 2004 and 2010, who followed one of the 4 management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log10VL from VF, using inverse probability weighting of marginal structural linear models.

Results: Nine hundred eighty-two patients were followed over 54,168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% confidence interval [CI], 0.2-2.8) and declines in log10VL of -1.4 copies/mL (95% CI, -2.0, -0.8), while switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI, -12.1, 1.3) and -5.6% (95% CI, -15.4, 4.1) and virologic outcomes (0.2 (95% CI, -3.6, 4.1) and 0.8 (95% CI, -0.6, 2.1), respectively.

Conclusions: The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies.
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http://dx.doi.org/10.1097/INF.0000000000002156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355383PMC
April 2019

Assessing the completeness and accuracy of South African National Laboratory CD4 and viral load data: a cross-sectional study.

BMJ Open 2018 08 23;8(8):e021506. Epub 2018 Aug 23.

Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objective: To assess the accuracy of the South African National Health Laboratory Services (NHLS) corporate data warehouse (CDW) using a novel data cross-matching method.

Methods: Adults (≥18 years) on antiretroviral therapy (ART) who visited a hospital-based HIV clinic in Durban from March to June 2012 were included. We matched patient identifiers, CD4 and viral load (VL) records from the HIV clinic's electronic record with the NHLS CDW according to a set of matching criteria for patient identifiers, test values and test dates. We calculated the matching rates for patient identifiers, CD4 and VL records, and an overall matching rate.

Results: NHLS returned records for 3498 (89.6%) of the 3906 individuals requested. Using our computer algorithm, we confidently matched 3278 patients (83.9% of the total request). Considering less than confident matches as well, and then manually reviewing questionable matches using only patient identifiers, only nine (0.3% of records returned by NHLS) of the suggested matches were judged incorrect.

Conclusions: We developed a data cross-matching method to evaluate national laboratory data and were able to match almost 9 of 10 patients with data we expected to find in the NHLS CDW. We found few questionable matches, suggesting that manual review of records returned was not essential. As the number of patients initiating ART in South Africa grows, maintaining a comprehensive and accurate national data repository is of critical importance, since it may serve as a valuable tool to evaluate the effectiveness of the country's HIV care system. This study helps validate the use of NHLS CDW data in future research on South Africa's HIV care system and may inform analyses in similar settings with national laboratory systems.
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http://dx.doi.org/10.1136/bmjopen-2018-021506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112393PMC
August 2018

Brief Report: Assessing the Association Between Changing NRTIs When Initiating Second-Line ART and Treatment Outcomes.

J Acquir Immune Defic Syndr 2018 04;77(4):413-416

Center for Global Health and Development, Boston University, Boston, MA.

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/mm.

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.
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http://dx.doi.org/10.1097/QAI.0000000000001611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825249PMC
April 2018

Clinic-Based Urinary Lipoarabinomannan as a Biomarker of Clinical Disease Severity and Mortality Among Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Infected Adults in South Africa.

Open Forum Infect Dis 2017 14;4(3):ofx167. Epub 2017 Aug 14.

Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.

Background: Urinary lipoarabinomannan (LAM) has limited sensitivity for diagnosing active human immunodeficiency virus (HIV)-associated tuberculosis (TB) disease, but LAM screening at HIV diagnosis might identify adults with more severe clinical disease or greater risk of mortality.

Methods: We enrolled antiretroviral therapy-naive HIV-infected adults from 4 clinics in Durban. Nurses performed urine LAM testing using a rapid assay (Determine TB LAM) graded from low (1+) to high (≥3+) intensity. Urine LAM results were not used to guide anti-TB therapy. We assessed TB-related symptoms and obtained sputum for mycobacterial smear and culture. Participants were observed for 12 months, and we used multivariable Cox proportional hazard models to determine hazard ratios for all-cause mortality.

Results: Among 726 HIV-infected adults with median CD4 of 205 cells/mm (interquartile range, 79-350 cells/mm), 93 (13%) were LAM positive and 89 (12%) participants died during the follow-up period. In multivariable analyses, urine LAM-positive participants had a mortality hazard ratio (MHR) of 3.58 (95% confidence interval [CI], 2.20-5.81) for all-cause mortality. Among participants with mycobacterial-confirmed TB, urine LAM-positivity had a 2.91 (95% CI, 1.26-6.73) MHR for all participants and a 4.55 (95% CI, 1.71-12.1) MHR for participants with CD4 ≤100 cell/mm. Participants with LAM-positive TB had significantly more clinical signs and symptoms of disease, compared with participants with LAM-negative TB disease.

Conclusions: Among HIV-infected adults, urinary LAM-positive patients had more clinical disease severity and a 3-fold increase in 12-month mortality compared with those who were LAM negative.
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http://dx.doi.org/10.1093/ofid/ofx167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622366PMC
August 2017

Barriers to Care and 1-Year Mortality Among Newly Diagnosed HIV-Infected People in Durban, South Africa.

J Acquir Immune Defic Syndr 2017 04;74(4):432-438

*Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA; †Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA; ‡Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA; §Harvard Medical School, Boston, MA; ‖Harvard University Center for AIDS Research, Harvard University, Boston, MA; ¶Data Coordinating Center, Boston University School of Public Health, Boston, MA; #McCord Hospital, Durban, South Africa; **Division of General Pediatrics, Department of Medicine, Boston Children's Hospital, Boston, MA; ††RAND Corporation, Santa Monica, CA; ‡‡St. Mary's Hospital, Durban, South Africa; §§Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA; ‖‖Department of Epidemiology, Boston University School of Public Health, Boston, MA; ¶¶Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, MA; ##Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA; and ***Department of Biostatistics, Boston University School of Public Health, Boston, MA.

Background: Prompt entry into HIV care is often hindered by personal and structural barriers. Our objective was to evaluate the impact of self-perceived barriers to health care on 1-year mortality among newly diagnosed HIV-infected individuals in Durban, South Africa.

Methods: Before HIV testing at 4 outpatient sites, adults (≥18 years) were surveyed regarding perceived barriers to care including (1) service delivery, (2) financial, (3) personal health perception, (4) logistical, and (5) structural. We assessed deaths via phone calls and the South African National Population Register. We used multivariable Cox proportional hazards models to determine the association between number of perceived barriers and death within 1 year.

Results: One thousand eight hundred ninety-nine HIV-infected participants enrolled. Median age was 33 years (interquartile range: 27-41 years), 49% were females, and median CD4 count was 192/μL (interquartile range: 72-346/μL). One thousand fifty-seven participants (56%) reported no, 370 (20%) reported 1-3, and 460 (24%) reported >3 barriers to care. By 1 year, 250 [13%, 95% confidence interval (CI): 12% to 15%] participants died. Adjusting for age, sex, education, baseline CD4 count, distance to clinic, and tuberculosis status, participants with 1-3 barriers (adjusted hazard ratio: 1.49, 95% CI: 1.06 to 2.08) and >3 barriers (adjusted hazard ratio: 1.81, 95% CI: 1.35 to 2.43) had higher 1-year mortality risk compared with those without barriers.

Conclusions: HIV-infected individuals in South Africa who reported perceived barriers to medical care at diagnosis were more likely to die within 1 year. Targeted structural interventions, such as extended clinic hours, travel vouchers, and streamlined clinic operations, may improve linkage to care and antiretroviral therapy initiation for these people.
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http://dx.doi.org/10.1097/QAI.0000000000001277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321110PMC
April 2017

Rapid urine lipoarabinomannan assay as a clinic-based screening test for active tuberculosis at HIV diagnosis.

BMC Pulm Med 2016 11 14;16(1):147. Epub 2016 Nov 14.

Medical Practice Evaluation Center, Harvard Medical School, Boston, USA.

Background: World Health Organization (WHO) recommends tuberculosis (TB) screening at HIV diagnosis. We evaluated the inclusion of rapid urine lipoarabinomannan (LAM) testing in TB screening algorithms.

Methods: We enrolled ART-naïve adults who screened HIV-infected in KwaZulu-Natal, assessed TB-related symptoms (cough, fever, night sweats, weight loss), and obtained sputum specimens for mycobacterial culture. Trained nurses performed clinic-based urine LAM testing using a rapid assay. We used diagnostic accuracy, negative predictive value (NPV), and negative likelihood ratio, stratified by CD4 count, to evaluate screening for culture-positive TB.

Results: Among 675 HIV-infected adults with median CD4 of 213/mm (interquartile range 85-360/mm), 123 (18%) had culture-confirmed pulmonary TB. The WHO-recommended algorithm of any TB-related symptom had a sensitivity of 77% [95% confidence interval (CI) 69-84%] and NPV of 89% (95% CI 84-92%) for identifying active pulmonary TB. Including the LAM assay improved sensitivity (83%; 95% CI 75-89%) and NPV (91%; 95% CI 86-94%), while decreasing the negative likelihood ratio (0.45 versus 0.57). Among participants with CD4 < 100/mm, including urine LAM testing improved the negative predictive value of symptom based screening from 83% to 87%. All screening algorithms with urine LAM performed better among participants with CD4 < 100/mm, compared to those with CD4 ≥ 100/mm.

Conclusion: Clinic-based urine LAM screening increased the sensitivity of symptom-based screening by 6% among ART-naïve HIV-infected adults in a TB-endemic setting, thereby providing marginal benefit.
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http://dx.doi.org/10.1186/s12890-016-0316-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109839PMC
November 2016

Sizanani: A Randomized Trial of Health System Navigators to Improve Linkage to HIV and TB Care in South Africa.

J Acquir Immune Defic Syndr 2016 Oct;73(2):154-60

Divisions of *Infectious Diseases;†General Medicine, Massachusetts General Hospital, Boston, MA;‡Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA;§Harvard Medical School, Boston, MA;‖Harvard University Center for AIDS Research, Harvard University, Boston, MA;¶Data Coordinating Center, Boston University School of Public Health, Boston, MA;#McCord Hospital, Durban, South Africa;**Division of General Pediatrics, Department of Medicine, Boston Children's Hospital, Boston, MA;††St. Mary's Hospital, Durban, South Africa;‡‡Department of Epidemiology, Boston University School of Public Health, Boston, MA;§§Department of Health Policy and Management, Harvard School of Public Health, Boston, MA;Divisions of ‖‖Rheumatology;¶¶Infectious Diseases, Brigham and Women's Hospital, Boston, MA;##Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA; and***Department of Biostatistics, Boston University School of Public Health, Boston, MA.

Background: A fraction of HIV-diagnosed individuals promptly initiate antiretroviral therapy (ART). We evaluated the efficacy of health system navigators for improving linkage to HIV and tuberculosis (TB) care among newly diagnosed HIV-infected outpatients in Durban, South Africa.

Methods: We conducted a randomized controlled trial (Sizanani Trial, NCT01188941) among adults (≥18 years) at 4 sites. Participants underwent TB screening and randomization into a health system navigator intervention or usual care. Intervention participants had an in-person interview at enrollment and received phone calls and text messages over 4 months. We assessed 9-month outcomes via medical records and the National Population Registry. Primary outcome was completion of at least 3 months of ART or 6 months of TB treatment for coinfected participants.

Results: Four thousand nine hundred three participants were enrolled and randomized; 1899 (39%) were HIV-infected, with 1146 (60%) ART-eligible and 523 (28%) TB coinfected at baseline. In the intervention, 212 (39% of outcome-eligible) reached primary outcome compared to 197 (42%) in usual care (RR 0.93, 95% CI: 0.80 to 1.08). One hundred thirty-one (14%) HIV-infected intervention participants died compared to 119 (13%) in usual care; death rates did not differ between arms (RR 1.06, 95% CI: 0.84 to 1.34). In the as-treated analysis, participants reached for ≥5 navigator calls were more likely to achieve study outcome.

Conclusions: ∼40% of ART-eligible participants in both study arms reached the primary outcome 9 months after HIV diagnosis. Low rates of engagement in care, high death rates, and lack of navigator efficacy highlight the urgency of identifying more effective strategies for improving HIV and TB care outcomes.
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http://dx.doi.org/10.1097/QAI.0000000000001025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026386PMC
October 2016

Optimal timing of antiretroviral treatment initiation in HIV-positive children and adolescents: a multiregional analysis from Southern Africa, West Africa and Europe.

Int J Epidemiol 2017 04;46(2):453-465

Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.

Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents.

Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula.

Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm 3 (394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm 3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes.

Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.
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http://dx.doi.org/10.1093/ije/dyw097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837574PMC
April 2017

Cervical Abnormalities in South African Women Living With HIV With High Screening and Referral Rates.

J Glob Oncol 2016 Dec 4;2(6):375-380. Epub 2016 May 4.

and , Brigham and Women's Hospital; , , and , Harvard Medical School; , Massachusetts General Hospital Center for Global Health; , Boston Children's Hospital; , Dana-Farber Cancer Institute; , Boston University, Boston, MA; , University of KwaZulu-Natal, Durban; , Western Cape Province Department of Health, Cape Town; , R.K. Khan Hospital, Chatsworth, South Africa; and , Canadian Red Cross, Ontario, Canada.

Purpose: To determine the prevalence of screening, cervical dysplasia, and malignancy on the basis of histologic diagnoses from colposcopy and large loop excision of the transformation zone among women living with HIV (WLWH) who attended an urban antiretroviral treatment (ART) clinic in KwaZulu-Natal, South Africa.

Materials And Methods: We performed a retrospective cohort study to examine a random sample of 462 WLWH during a 5-year period from 2004 to 2009. Women on ART for < 3 months were excluded. Data were abstracted from electronic records and paper charts to assess rates of cervical abnormalities detected on Pap smears as well as time to colposcopy.

Results: During the study period, 432 women (93.5%) had at least one evaluable Papanicolau test. At baseline, 237 women (54.9%) had an abnormal Papanicolau test, and of these patients, 181 (76.3%) had a Papanicolau test that qualified for further colposcopic evaluation. In addition, 115 women (63.5%) received colposcopy within a median of 39 days from referral. This yielded 74 evaluable histologic samples (64.3%), of which 21.6%, 27.0%, 27.0%, and 1.4% had cervical intraepithelial neoplasia (CIN) 1, CIN2, CIN3, and invasive cervical cancer, respectively.

Conclusion: In a large sample of WLWH who received ART in KwaZulu-Natal, South Africa, where Papanicolau test coverage and rates of referral for colposcopy and large loop excision of the transformation zone were high, > 75% of women with evaluable histologic samples had evidence of cervical dysplasia or malignancy. These findings underscore the importance of routine cervical screening upon entry into HIV care to optimize survival.
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http://dx.doi.org/10.1200/JGO.2015.002469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493244PMC
December 2016

Record linkage to correct under-ascertainment of cancers in HIV cohorts: The Sinikithemba HIV clinic linkage project.

Int J Cancer 2016 09 18;139(6):1209-16. Epub 2016 May 18.

Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.

The surveillance of HIV-related cancers in South Africa is hampered by the lack of systematic collection of cancer diagnoses in HIV cohorts and the absence of HIV status in cancer registries. To improve cancer ascertainment and estimate cancer incidence, we linked records of adults (aged ≥ 16 years) on antiretroviral treatment (ART) enrolled at Sinikithemba HIV clinic, McCord Hospital in KwaZulu-Natal (KZN) with the cancer records of public laboratories in KZN province using probabilistic record linkage (PRL) methods. We calculated incidence rates for all cancers, Kaposi sarcoma (KS), cervix, non-Hodgkin's lymphoma and non-AIDS defining cancers (NADCs) before and after inclusion of linkage-identified cancers with 95% confidence intervals (CIs). A total of 8,721 records of HIV-positive patients were linked with 35,536 cancer records. Between 2004 and 2010, we identified 448 cancers, 82% (n = 367) were recorded in the cancer registry only, 10% (n = 43) in the HIV cohort only and 8% (n = 38) both in the HIV cohort and the cancer registry. The overall cancer incidence rate in patients starting ART increased from 134 (95% CI 91-212) to 877 (95% CI 744-1,041) per 100,000 person-years after inclusion of linkage-identified cancers. Incidence rates were highest for KS (432, 95% CI 341-555), followed by cervix (259, 95% CI 179-390) and NADCs (294, 95% CI 223-395) per 100,000 person-years. Ascertainment of cancer in HIV cohorts is incomplete, PRL is both feasible and essential for cancer ascertainment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084785PMC
http://dx.doi.org/10.1002/ijc.30154DOI Listing
September 2016

Growth of HIV-Exposed Uninfected Infants in the First 6 Months of Life in South Africa: The IeDEA-SA Collaboration.

PLoS One 2016 6;11(4):e0151762. Epub 2016 Apr 6.

School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.

Background: HIV-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa especially with the increasing coverage of more effective prevention of mother-to-child transmission (PMTCT) antiretroviral therapy regimens. This study describes the characteristics of South African HEU infants, investigates factors impacting birth weight and assesses their growth within the first 28 weeks of life.

Methods: This is a retrospective cohort based on routine clinical data from two South African PMTCT programmes. Data were collected between 2007 and 2013. Linear regression assessed factors affecting birth weight-for-age z-scores (WAZ) while growth (longitudinal WAZ) was assessed using mixed effects models.

Results: We assessed the growth of 2621 HEU infants (median birth WAZ was -0.65 (IQR -1.46; 0.0) and 51% were male). The feeding modalities practised were as follows: 0.5% exclusive breastfeeding, 7.9% breastfeeding with unknown exclusivity, 0.08% mixed breastfeeding and 89.2% formula feeding. Mothers with CD4 <200 cells/μl delivered infants with a lower birth WAZ (adjusted ß -0.253 [95% CI -0.043; -0.072], p = 0.006) compared to mothers with aCD4 ≥500 cells/μl. Similarly, mothers who did not receive antiretroviral drugs delivered infants with a lower birth WAZ (adjusted ß -0.39 [95% CI -0.67; -0.11], p = 0.007) compared to mothers who received antenatal antiretrovirals. Infants with a birth weight <2 500g (ß 0.070 [95% CI 0.061; 0.078], p <0.0001) experienced faster growth within the first 28 weeks of life compared to infants with a birth weight ≥2 500g. Infants with any breastfeeding exposure experienced slower longitudinal growth compared to formula fed infants (adjusted ß -0.012 [95% CI 0.021; -0.003], p = 0.011).

Conclusion: Less severe maternal disease and the use of antiretrovirals positively impacts birth weight in this cohort of South African HEU infants. Formula feeding was common with breastfed infants experiencing marginally slower longitudinal growth.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151762PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822941PMC
August 2016

Growth and Mortality Outcomes for Different Antiretroviral Therapy Initiation Criteria in Children Ages 1-5 Years: A Causal Modeling Analysis.

Epidemiology 2016 Mar;27(2):237-46

From the aCentre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa; bInstitute of Epidemiology and Public Health, University of Bordeaux, Bordeaux, France; cUniversity of Ghana Medical School, Accra, Ghana; dWits Reproductive Health and HIV Institute, Harriet Shezi Children's Clinic, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Soweto, South Africa; eCentre de Prise en Charge de Recherche et de Formation Enfants, Abidjan, Côte d'Ivoire; fEmpilweni Service and Research Unit, Rahima Moosa Mother and Child Hospital and University of the Witwatersrand, Johannesburg, South Africa; gYopougon University Hospital, Abidjan, Côte d'Ivoire; hAfrica Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa; iAlbert Royer Hospital, Dakar, Senegal; jLighthouse Trust Clinic, Kamuzu Central Hospital, Lilongwe, Malawi; kUniversity of North Carolina, Chapel Hill, NC; lFélix Houphouët Boigny University Hospital, Abidjan, Côte d'Ivoire; mMédecins Sans Frontiéres South Africa, CapeTown, South Africa; nKhayelitsha ART Programme, Khayelitsha, Cape Town, South Africa; oCharles de Gaulle University Hospital, Ouagadougou, Burkina Faso; pNewlands Clinic, Harare, Zimbabwe; qHospital du Tokoin, Lomé, Togo; rSinikithemba Clinic, McCord Hospital, Durban, South Africa; sMTCT-Plus Center, Abidjan, Côte d'Ivoire; tDesmond Tutu HIV Centre, Cape Town, South Africa; uInstitute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; vInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; and wInserm, U897, Epidémiologie-Biostatistiques, Université Bordeaux, Bordeaux, France.

Background: There is limited evidence regarding the optimal timing of initiating antiretroviral therapy (ART) in children. We conducted a causal modeling analysis in children ages 1-5 years from the International Epidemiologic Databases to Evaluate AIDS West/Southern-Africa collaboration to determine growth and mortality differences related to different CD4-based treatment initiation criteria, age groups, and regions.

Methods: ART-naïve children of ages 12-59 months at enrollment with at least one visit before ART initiation and one follow-up visit were included. We estimated 3-year growth and cumulative mortality from the start of follow-up for different CD4 criteria using g-computation.

Results: About one quarter of the 5,826 included children was from West Africa (24.6%).The median (first; third quartile) CD4% at the first visit was 16% (11%; 23%), the median weight-for-age z-scores and height-for-age z-scores were -1.5 (-2.7; -0.6) and -2.5 (-3.5; -1.5), respectively. Estimated cumulative mortality was higher overall, and growth was slower, when initiating ART at lower CD4 thresholds. After 3 years of follow-up, the estimated mortality difference between starting ART routinely irrespective of CD4 count and starting ART if either CD4 count <750 cells/mm³ or CD4% <25% was 0.2% (95% CI = -0.2%; 0.3%), and the difference in the mean height-for-age z-scores of those who survived was -0.02 (95% CI = -0.04; 0.01). Younger children ages 1-2 and children in West Africa had worse outcomes.

Conclusions: Our results demonstrate that earlier treatment initiation yields overall better growth and mortality outcomes, although we could not show any differences in outcomes between immediate ART and delaying until CD4 count/% falls below 750/25%.
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http://dx.doi.org/10.1097/EDE.0000000000000412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410645PMC
March 2016

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.

J Acquir Immune Defic Syndr 2015 Nov;70(3):e110-9

*Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; †Kheth'Impilo, Cape Town, South Africa; ‡Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; §Aurum Institute for Health Research, Johannesburg, South Africa; ‖Gugulethu ART Programme and Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa; ¶Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa; #Médecins Sans Frontières, Khayelitsha, Cape Town, South Africa; **Sinikithemba Clinic, McCord Hospital, Durban, South Africa; ††Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa; ‡‡Health Economics and Epidemiology Research Office, University of the Witwatersrand, Johannesburg, South Africa; §§Center for Global Health & Development and Department of Epidemiology, Boston University, Boston, MA; ‖‖Biostatistics and Databases Program, The Kirby Institute, Faculty of Medicine, The University of New South Wales, Sydney, Australia; and ¶¶Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, South Africa.

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.
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http://dx.doi.org/10.1097/QAI.0000000000000748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395665PMC
November 2015

Age in antiretroviral therapy programmes in South Africa: a retrospective, multicentre, observational cohort study.

Lancet HIV 2015 Sep 4;2(9):e368-75. Epub 2015 Aug 4.

Centre for Infectious Disease Epidemiology and Research, Cape Town, South Africa; Division of Epidemiology and Biostatistics, Cape Town, South Africa.

Background: As access to antiretroviral therapy (ART) expands, increasing numbers of older patients will start treatment and need specialised long-term care. However, the effect of age in ART programmes in resource-constrained settings is poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of the highest HIV population prevalences worldwide. We explored the effect of age on mortality of patients on ART in South Africa and whether this effect is mediated by baseline immunological status.

Methods: In this retrospective cohort analysis, we studied HIV-positive patients aged 16-80 years who started ART for the first time in six large South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, in KwaZulu-Natal, Gauteng, and Western Cape (two primary care clinics, three hospitals, and a large rural cohort). The primary outcome was mortality. We ascertained patients' vital status through linkage to the National Population Register. We used inverse probability weighting to correct mortality for loss to follow-up. We estimated mortality using Cox's proportional hazards and competing risks regression. We tested the interaction between baseline CD4 cell count and age.

Findings: Between Jan 1, 2004, and Dec 31, 2013, 84,078 eligible adults started ART. Of these, we followed up 83,566 patients for 174,640 patient-years. 8% (1817 of 23,258) of patients aged 16-29 years died compared with 19% (93 of 492) of patients aged 65 years or older. The age adjusted mortality hazard ratio was 2·52 (95% CI 2·01-3·17) for people aged 65 years or older compared with those 16-29 years of age. In patients starting ART with a CD4 count of less than 50 cells per μL, the adjusted mortality hazard ratio was 2·52 (2·04-3·11) for people aged 50 years or older compared with those 16-39 years old. Mortality was highest in patients with CD4 counts of less than 50 cells per μL, and 15% (1103 of 7295) of all patients aged 50 years or older starting ART were in this group. The proportion of patients aged 50 years or older enrolling in ART increased with successive years, from 6% (290 of 4999) in 2004 to 10% (961 of 9657) in 2012-13, comprising 9% of total enrolment (7295 of 83 566). At the end of the study, 6304 (14%) of 44,909 patients still alive and in care were aged 50 years or older.

Interpretation: Health services need reorientation towards HIV diagnosis and starting of ART in older individuals. Policies are needed for long-term care of older people with HIV.

Funding: National Institutes of Health (National Institute of Allergy and Infectious Diseases), US Agency for International Development, and South African Centre for Epidemiological Modelling and Analysis.
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http://dx.doi.org/10.1016/S2352-3018(15)00113-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603282PMC
September 2015

Reducing CD4 Monitoring in Children on Antiretroviral Therapy With Virologic Suppression.

Pediatr Infect Dis J 2015 Dec;34(12):1361-4

From the *Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; †HIV/AIDS Department, World Health Organization, Geneva, Switzerland; ‡Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch, South Africa; §Kheth'Impilo, Cape Town, South Africa; ¶Médecins Sans Frontières, Khayelitsha, South Africa; ‖McCord Hospital, Durban, South Africa; **Hlabisa HIV Program, South Africa; ††Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa; ‡‡Wits Reproductive Health and HIV Institute, University of Witwatersrand, Johannesburg, South Africa; §§Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; ¶¶Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa; ‖‖Gugulethu HIV Program, Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa; ***Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, Maryland; and †††Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Background: Ongoing CD4 monitoring in patients on antiretroviral therapy (ART) with viral suppression has been questioned. We evaluated the probability of CD4 decline in children with viral suppression and CD4 recovery after 1 year on ART.

Methods: We included children from 8 South African cohorts with routine HIV-RNA monitoring if (1) they were "responders" [HIV-RNA < 400 copies/mL and no severe immunosuppression after ≥1 year on ART (time 0)] and (2) ≥1 HIV-RNA and CD4 measurement within 15 months of time 0. We determined the probability of CD4 decline to World Health Organization-defined severe immunosuppression for 3 years after time 0 if viral suppression was maintained. Follow-up was censored at the earliest of the following dates: the day before first HIV-RNA measurement >400 copies/mL; day before a >15-month gap in testing and date of death, loss to follow-up, transfer out or database closure.

Results: Among 5984 children [median age at time 0: 5.8 years (interquartile range: 3.1-9.0)], 270 children experienced a single CD4 decline to severe immunosuppression within 3 years of time 0 with probability of 6.6% (95% CI: 5.8-7.4). A subsequent CD4 measurement within 15 months of the first low measurement was available for 63% of children with CD4 decline and 86% showed CD4 recovery. The probability of CD4 decline was lowest (2.8%) in children aged 2 years or older with no or mild immunosuppression and on ART for <18 months at time 0. This group comprised 40% of children.

Conclusions: This finding suggests that it may be safe to stop routine CD4 monitoring in children older than 2 years and rely on virologic monitoring alone.
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http://dx.doi.org/10.1097/INF.0000000000000912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384719PMC
December 2015

Understanding HIV-infected patients' experiences with PEPFAR-associated transitions at a Centre of Excellence in KwaZulu Natal, South Africa: a qualitative study.

AIDS Care 2015 24;27(10):1298-303. Epub 2015 Aug 24.

e Harvard University Center for AIDS Research (CFAR) , Boston , MA , USA.

South Africa was the largest recipient of funding from the President's Emergency Plan for AIDS Relief (PEPFAR) for antiretroviral therapy (ART) programs from 2004 to 2012. Funding decreases have led to transfers from hospital and non-governmental organization-based care to government-funded, community-based clinics. We conducted semi-structured interviews with 36 participants to assess patient experiences related to transfer of care from a PEPFAR-funded, hospital-based clinic in Durban to either primary care clinics or hospital-based clinics. Participant narratives revealed the importance of connectedness between patients and the PEPFAR-funded clinic program staff, who were described as respectful and conscientious. Participants reported that transfer clinics were largely focused on dispensing medication and on throughput, rather than holistic care. Although participants appreciated the free treatment at transfer sites, they expressed frustration with long waiting times and low perceived quality of patient-provider communication, and felt that they were treated disrespectfully. These factors eroded confidence in the quality of the care. The transfer was described by participants as hurried with an apparent lack of preparation at transfer clinics for new patient influx. Formal (e.g., counseling) and informal (e.g., family) social supports, both within and beyond the PEPFAR-funded clinic, provided a buffer to challenges faced during and after the transition in care. These data support the importance of social support, adequate preparation for transfer, and improving the quality of care in receiving clinics, in order to optimize retention in care and long-term adherence to treatment.
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http://dx.doi.org/10.1080/09540121.2015.1051502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548805PMC
February 2018

Social support and mental health among adults prior to HIV counseling and testing in Durban, South Africa.

AIDS Care 2015 25;27(10):1231-40. Epub 2015 Jul 25.

a Division of Infectious Diseases , Massachusetts General Hospital , Boston , MA , USA.

Poor social support and mental health may be important modifiable risk factors for HIV acquisition, but they have not been evaluated prior to HIV testing in South Africa. We sought to describe self-perceived mental health and social support and to characterize their independent correlates among adults who presented for voluntary HIV testing in Durban. We conducted a large cross-sectional study of adults (≥18 years of age) who presented for HIV counseling and testing between August 2010 and January 2013 in Durban, South Africa. We enrolled adults presenting for HIV testing and used the Medical Outcomes Study's Social Support Scale (0 [poor] to 100 [excellent]) and the Mental Health Inventory (MHI-3) to assess social support and mental health. We conducted independent univariate and multivariable linear regression models to determine the correlates of lower self-reported Social Support Index and lower self-reported MCH scores. Among 4874 adults surveyed prior to HIV testing, 1887 (39%) tested HIV-positive. HIV-infected participants reported less social support (mean score 66 ± 22) and worse mental health (mean score 66 ± 16), compared to HIV-negative participants (74 ± 21; 70 ± 18; p < 0.0001). In a multivariable analysis, significant correlates of less social support included presenting for HIV testing at an urban hospital, not having been tested previously, not working outside the home, and being HIV-infected. In a separate multivariable analysis, significant correlates of poor mental health were similar, but also included HIV testing at an urban hospital and being in an intimate relationship less than six months. In this study, HIV-infected adults reported poorer social support and worse mental health than HIV-negative individuals. These findings suggest that interventions to improve poor social support and mental health should be focused on adults who do not work outside the home and those with no previous HIV testing.
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http://dx.doi.org/10.1080/09540121.2015.1046417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607562PMC
February 2018

Growth in Virologically Suppressed HIV-Positive Children on Antiretroviral Therapy: Individual and Population-level References.

Pediatr Infect Dis J 2015 Oct;34(10):e254-9

From the *Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland; †School of Public Health and Family Medicine, University of Cape Town, South Africa; ‡Leuven Institute for Research on Information Systems, KU Leuven, Belgium; §Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; ¶Wits Reproductive Health and HIV Institute (Harriet Shezi Children's Clinic, Chris Hani Baragwanath Hospital, Soweto), University of Witwatersrand, Johannesburg, South Africa; ‖Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch, South Africa; **Empilweni Services and Research Unit (Rahima Moosa Mother and Child Hospital, Johannesburg) and University of Witwatersrand, Johannesburg, South Africa; ††Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa; ‡‡Médecins Sans Frontières (MSF) South Africa, Khayelitsha, Cape Town, South Africa; §§Sinikithemba Clinic, McCord Hospital, Johannesburg, South Africa; and ¶¶Kheth'Impilo, Cape Town, South Africa.

Background: Combination antiretroviral therapy (ART) suppresses viral replication in HIV-infected children. The growth of virologically suppressed children on ART has not been well documented. We aimed to develop dynamic reference curves for weight-for-age Z scores (WAZ) and height-for-age Z scores (HAZ).

Methods: Children aged <11 years at ART initiation with continuously undetectable viral loads (<400 copies/mL) treated at 7 South African ART programs with routine viral load monitoring were included. We used multilevel models to define trajectories of WAZ and HAZ up to 3 years and developed a web application to monitor trajectories in individual children.

Results: A total of 4876 children were followed for 7407 person-years. Analyses were stratified by baseline Z scores and age, which were the most important predictors of growth response. The youngest children showed the most pronounced increase in weight and height initially but catch-up growth stagnated after 1-2 years. Three years after starting ART, WAZ ranged from -2.2 [95% prediction interval (PrI), -5.6 to 0.8] in children with baseline age >5 years and Z score less than -3 to 0.0 (95% PrI, -2.7 to 2.4) in children with baseline age <2 years and WAZ greater than -1. For HAZ, the corresponding range was -2.3 (95% PrI, -4.9 to 0.3) in children with baseline age >5 years and Z score less than -3 to 0.3 (95% PrI, -3.1 to 3.4) in children with baseline age 2-5 years and HAZ greater than -1.

Conclusions: We have developed an online tool to calculate reference trajectories in fully suppressed children. The web application could help to define "optimal" growth response and identify children with treatment failure.
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http://dx.doi.org/10.1097/INF.0000000000000801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570854PMC
October 2015

Outcomes of Infants Starting Antiretroviral Therapy in Southern Africa, 2004-2012.

J Acquir Immune Defic Syndr 2015 Aug;69(5):593-601

*School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; †MMed Paeds and Child Health (UNZA), Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; ‡Tygerberg Academic Hospital and Stellenbosch University, Cape Town, South Africa; §Lighthouse Trust Clinic, Lilongwe, Malawi; ‖Red Cross War Memorial Children's Hospital, Cape Town, South Africa; ¶School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa; #Wits Reproductive Health and HIV Institute (Wits RHI), University of the Witwatersrand, Johannesburg, South Africa; **Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital and University of the Witwatersrand, Johannesburg, South Africa; ††Médecins Sans Frontierès, Khayelitsha and School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; ‡‡Gugulethu Community Health Centre and Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; §§Newlands Clinic, Harare, Zimbabwe; ‖‖Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland; ¶¶McCord Hospital, Durban, South Africa; and ##Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa.

Background: There are limited published data on the outcomes of infants starting antiretroviral therapy (ART) in routine care in Southern Africa. This study aimed to examine the baseline characteristics and outcomes of infants initiating ART.

Methods: We analyzed prospectively collected cohort data from routine ART initiation in infants from 11 cohorts contributing to the International Epidemiologic Database to Evaluate AIDS in Southern Africa. We included ART-naive HIV-infected infants aged <12 months initiating ≥3 antiretroviral drugs between 2004 and 2012. Kaplan-Meier estimates were calculated for mortality, loss to follow-up (LTFU), transfer out, and virological suppression. We used Cox proportional hazard models stratified by cohort to determine baseline characteristics associated with outcomes mortality and virological suppression.

Results: The median (interquartile range) age at ART initiation of 4945 infants was 5.9 months (3.7-8.7) with follow-up of 11.2 months (2.8-20.0). At ART initiation, 77% had WHO clinical stage 3 or 4 disease and 87% were severely immunosuppressed. Three-year mortality probability was 16% and LTFU 29%. Severe immunosuppression, WHO stage 3 or 4, anemia, being severely underweight, and initiation of treatment before 2010 were associated with higher mortality. At 12 months after ART initiation, 17% of infants were severely immunosuppressed and the probability of attaining virological suppression was 56%.

Conclusions: Most infants initiating ART in Southern Africa had severe disease with high probability of LTFU and mortality on ART. Although the majority of infants remaining in care showed immune recovery and virological suppression, these responses were suboptimal.
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http://dx.doi.org/10.1097/QAI.0000000000000683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509628PMC
August 2015

Pregnant women's experiences of male partner involvement in the context of prevention of mother-to-child transmission in Khayelitsha, South Africa.

AIDS Care 2015 4;27(8):1020-4. Epub 2015 Mar 4.

a School of Public Health & Family Medicine , University of Cape Town , Cape Town , South Africa.

Male partner involvement (MPI) has been identified as a priority intervention in programmes for the prevention of mother-to-child transmission (PMTCT) of HIV, but rates of MPI remain low worldwide. This study used a quantitative survey (n=170) and two focus group discussions (FGDs) with 16 HIV-positive pregnant women attending a public sector antenatal care service in Khayelitsha, South Africa, to examine the determinants of high levels of involvement and generate a broader understanding of women's experiences of MPI during pregnancy. Among survey participants, 74% had disclosed their status to their partner, and most reported high levels of communication around HIV testing and preventing partner transmission, as well as high levels of MPI. High MPI was significantly more likely among women who were cohabiting with their partner; who had reportedly disclosed their HIV status to their partner; and who reported higher levels of HIV-related communication with their partner. FGD participants discussed a range of ways in which partners can be supportive during pregnancy, not limited to male attendance of antenatal care. MPI appears to be a feasible intervention in this context, and MPI interventions should aim to encourage male partner attendance of antenatal care as well as greater involvement in pregnancy more generally. Interventions that target communication are needed to facilitate HIV-related communication and disclosure within couples. MPI should remain a priority intervention in PMTCT programmes, and increased efforts should be made to promote MPI in PMTCT.
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http://dx.doi.org/10.1080/09540121.2015.1018862DOI Listing
January 2016

The Linkage Outcomes of a Large-scale, Rapid Transfer of HIV-infected Patients From Hospital-based to Community-based Clinics in South Africa.

Open Forum Infect Dis 2014 Sep 12;1(2):ofu058. Epub 2014 Aug 12.

Division of General Medicine ; Medical Practice Evaluation Center, Department of Medicine ; Division of Infectious Disease , Massachusetts General Hospital ; Harvard University Center for AIDS Research (CFAR).

Background: President's Emergency Plan for AIDS Relief (PEPFAR) funding changes have resulted in human immunodeficiency virus (HIV) clinic closures. We evaluated linkage to care following a large-scale patient transfer from a PEPFAR-funded, hospital-based HIV clinic to government-funded, community-based clinics in Durban.

Methods: All adults were transferred between March and June 2012. Subjects were surveyed 5-10 months post-transfer to assess self-reported linkage to the target clinic. We validated self-reports by auditing records at 8 clinics. Overall success of transfer was estimated using linkage to care data for both reached and unreached subjects, adjusted for validation results.

Results: Of the 3913 transferred patients, 756 (19%) were assigned to validation clinics; 659 (87%) of those patients were reached. Among those reached, 468 (71%) had a validated clinic record visit. Of the 46 who self-reported attending a different validation clinic than originally assigned, 39 (85%) had a validated visit. Of the 97 patients not reached, 59 (61%) had a validated visit at their assigned clinic. Based on the validation rates for reached and unreached patients, the estimated success of transfer for the cohort overall was 82%.

Conclusions: Most patients reported successful transfer to a community-based clinic, though a quarter attended a different clinic than assigned. Validation of attendance highlights that nearly 20% of patients may not have linked to care and may have experienced a treatment interruption. Optimizing transfers of HIV care to community sites requires collaboration with receiving clinics to ensure successful linkage to care.
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http://dx.doi.org/10.1093/ofid/ofu058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281821PMC
September 2014

Prevention of mother-to-child transmission in South Africa: an ever-changing landscape.

Obstet Med 2015 Mar 6;8(1):5-12. Epub 2015 Feb 6.

Médicins Sans Frontières, Cape Town, South Africa; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, South Africa.

Almost 30% of pregnant women attending public health clinics in South Africa are HIV positive; which represents approximately 280,000 women each year. South Africa has the largest antiretroviral therapy programme in the world, with over 2.7 million people on treatment in 2013. Since its belated and controversial beginning, the Prevention of Mother-to-Child Transmission programme has achieved a substantial reduction in vertical transmission. South Africa is justifiably proud of this success. However, the history of Prevention of Mother-to-Child Transmission (PMTCT) and antiretroviral therapy programmes in South Africa has been fraught with delays and political intervention. South Africa could have started both PMTCT and antiretroviral therapy programmes in 2000. Instead, the AIDS denialist views of the government allowed the HIV epidemic to spiral out of control. Roll-out of a national PMTCT programme began in 2002, but only after the government was forced to do so by a Constitutional Court ruling. Now, a decade later, HIV treatment and prevention programmes have been completely transformed. This article will discuss the evolution of the HIV epidemic in South Africa, and give a historical overview of the struggle to establish a national PMTCT, and the impact of delaying PMTCT and treatment programmes on infant and maternal health.
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http://dx.doi.org/10.1177/1753495X15570994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934997PMC
March 2015

Value of urine lipoarabinomannan grade and second test for optimizing clinic-based screening for HIV-associated pulmonary tuberculosis.

J Acquir Immune Defic Syndr 2015 Mar;68(3):274-80

*Department of Medicine, Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA; †Department of Medicine, Divisions of Infectious Diseases, Massachusetts General Hospital, Boston, MA; ‡Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; §General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA; ‖Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; ¶Boston University School of Public Health, Boston, MA; #Department of Medicine, McCord Hospital, Durban, South Africa; and **Department of Medicine, St. Mary's Hospital, Durban, South Africa.

Background: We assessed the role of urine lipoarabinomannan (LAM) grade and a second LAM test for HIV-associated pulmonary tuberculosis (TB) screening in outpatient clinics in South Africa.

Methods: We enrolled newly diagnosed HIV-infected adults (≥18 years) at 4 clinics, excluding those on TB therapy. Participants provided sputum for acid-fast bacilli (AFB) microscopy and culture. Nurses conducted 2 rapid urine LAM tests at the point-of-care and graded positive results from low (faint) to high (5+). Culture-confirmed pulmonary TB was the gold standard. We used area under receiver operating curves (AUROC) to compare screening strategies.

Results: Among 320 HIV-infected adults, median CD4 was 248 cells per cubic millimeter (interquartile range, 107-379/mm); 54 (17%) were TB culture positive. Fifty-two (16%) of all participants were LAM positive by either test; correlation between LAM tests was high. Among 10 "faint" positive results, 2 (20%) had culture-positive TB. Using ≥1+ LAM grade as positive, 1 LAM test had sensitivity of 41% [95% confidence interval (CI): 28% to 55%] and specificity of 92% (95% CI: 88% to 95%). A 2 LAM test strategy had a sensitivity of 43% (95% CI: 29% to 57%). One LAM test ≥1+ grade (AUROC = 0.66; 95% CI: 0.60 to 0.73) was significantly better than sputum AFB alone. The optimal strategy was sequentially performing 1 LAM test followed by sputum AFB if LAM grade <1+ (AUROC = 0.70; 95% CI: 0.63 to 0.77), which had sensitivity of 48% (95% CI: 34% to 62%) and specificity of 91% (95% CI: 87% to 94%).

Conclusions: In this clinic-based study, "faint" line was a false-positive second urine LAM test added no value, and an optimal screening strategy was 1 LAM test followed by sputum AFB microscopy for urine LAM-negative people.
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http://dx.doi.org/10.1097/QAI.0000000000000436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326555PMC
March 2015
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