Browsing by Author "Stinson K"

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Coverage of nevirapine-based services to prevent mother-to-child HIV transmission in 4 African countries.
(2010-Jul-21) Stringer EM; Ekouevi DK; Coetzee D; Tih PM; Creek TL; Stinson K; Giganti MJ; Welty TK; Chintu N; Chi BH; Wilfert CM; Shaffer N; Dabis F; Stringer JS; Centre for Infectious Disease Research in Zambia, Plot 1275 Lubutu Rd, PO Box 34681, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
CONTEXT: Few studies have objectively evaluated the coverage of services to prevent transmission of human immunodeficiency virus (HIV) from mother to child. OBJECTIVE: To measure the coverage of services to prevent mother-to-child HIV transmission in 4 African countries. DESIGN, SETTING, AND PATIENTS: Cross-sectional surveillance study of mother-infant pairs using umbilical cord blood samples collected between June 10, 2007, and October 30, 2008, from 43 randomly selected facilities (grouped as 25 service clusters) providing delivery services in Cameroon, Côte d'Ivoire, South Africa, and Zambia. All sites used at least single-dose nevirapine to prevent mother-to-child HIV transmission and some sites used additional prophylaxis drugs. MAIN OUTCOME MEASURE: Population nevirapine coverage, defined as the proportion of HIV-exposed infants in the sample with both maternal nevirapine ingestion (confirmed by cord blood chromatography) and infant nevirapine ingestion (confirmed by direct observation). RESULTS: A total of 27,893 cord blood specimens were tested, of which 3324 were HIV seropositive (12%). Complete data for cord blood nevirapine results were available on 3196 HIV-seropositive mother-infant pairs. Nevirapine coverage varied significantly by site (range: 0%-82%). Adjusted for country, the overall coverage estimate was 51% (95% confidence interval [CI], 49%-53%). In multivariable analysis, failed coverage of nevirapine-based services was significantly associated with maternal age younger than 20 years (adjusted odds ratio [AOR], 1.44; 95% CI, 1.18-1.76) and maternal age between 20 and 25 years (AOR, 1.28; 95% CI, 1.07-1.54) vs maternal age of older than 30 years; 1 or fewer antenatal care visits (AOR, 2.91; 95% CI, 2.40-3.54), 2 or 3 antenatal care visits (AOR, 1.93; 95% CI, 1.60-2.33), and 4 or 5 antenatal care visits (AOR, 1.56; 95% CI, 1.34-1.80) vs 6 or more antenatal care visits; vaginal delivery (AOR, 1.22; 95% CI, 1.03-1.44) vs cesarean delivery; and infant birth weight of less than 2500 g (AOR, 1.34; 95% CI, 1.11-1.62) vs birth weight of 3500 g or greater. CONCLUSION: In this random sampling of sites with services to prevent mother-to-child HIV transmission, only 51% of HIV-exposed infants received the minimal regimen of single-dose nevirapine.
Implementation and Operational Research: Reconstructing the PMTCT Cascade Using Cross-sectional Household Survey Data: The PEARL Study.
(2015-Sep-01) Chi BH; Tih PM; Zanolini A; Stinson K; Ekouevi DK; Coetzee D; Welty TK; Bweupe M; Shaffer N; Dabis F; Stringer EM; Stringer JS; *University of North Carolina at Chapel Hill, Chapel Hill, NC; †Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; ‡Cameroon Baptist Health Convention Health Board, Bamenda, Cameroon; §University of Cape Town, Cape Town, South Africa; ‖INSERM, Centre INSERM U897, Bordeaux, France; ¶University of Bordeaux, ISPED, Centre INSERM U897, Bordeaux, France; #Programme PAC-CI, Abidjan, Cote d'Ivoire; **Zambian Ministry of Health, Lusaka, Zambia; and ††World Health Organization, Geneva, Switzerland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Given the ambitious targets to reduce pediatric AIDS worldwide, ongoing assessment of programs to prevent mother-to-child HIV transmission (PMTCT) is critical. The concept of a "PMTCT cascade" has been used widely to identify bottlenecks in program implementation; however, most efforts to reconstruct the cascade have relied on facility-based approaches that may limit external validity. METHODS: We analyzed data from the PEARL household survey, which measured PMTCT effectiveness in 26 communities across Zambia, South Africa, Cote d'Ivoire, and Cameroon. We recruited women who reported a delivery in the past 2 years. Among mothers confirmed to be HIV infected at the time of survey, we reconstructed the PMTCT cascade with self-reported participant information. We also analyzed data about the child's vital status; for those still alive, HIV testing was performed by DNA polymerase chain reaction testing. RESULTS: Of the 976 eligible women, only 355 (36%) completed every step of the PMTCT cascade. Among the 621 mother-child pairs who did not, 22 (4%) reported never seeking antenatal care, 103 (17%) were not tested for HIV during pregnancy, 395 (64%) reported testing but never received their HIV-positive result, 48 (8%) did not receive maternal antiretroviral prophylaxis, and 53 (9%) did not receive infant antiretroviral prophylaxis. The lowest prevalence of infant HIV infection or death was observed in those completing the cascade (10%, 95% confidence interval: 7% to 12%). CONCLUSIONS: Future efforts to measure population PMTCT impact should incorporate dimensions explored in the PEARL study-including HIV testing of HIV-exposed children in household surveys-to better understand program effectiveness.
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 M; Fatti G; Chi BH; Keiser O; Hoffmann CJ; Wood R; Prozesky H; Stinson K; Giddy J; Mutevedzi P; Fox MP; Law M; Boulle A; Egger M; *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.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Measuring coverage in MNCH: population HIV-free survival among children under two years of age in four African countries.
(2013) Stringer JS; Stinson K; Tih PM; Giganti MJ; Ekouevi DK; Creek TL; Welty TK; Chi BH; Wilfert CM; Shaffer N; Stringer EM; Dabis F; Coetzee D; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. jeff_stringer@unc.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Population-based evaluations of programs for prevention of mother-to-child HIV transmission (PMTCT) are scarce. We measured PMTCT service coverage, regimen use, and HIV-free survival among children ≤24 mo of age in Cameroon, Côte D'Ivoire, South Africa, and Zambia. METHODS AND FINDINGS: We randomly sampled households in 26 communities and offered participation if a child had been born to a woman living there during the prior 24 mo. We tested consenting mothers with rapid HIV antibody tests and tested the children of seropositive mothers with HIV DNA PCR or rapid antibody tests. Our primary outcome was 24-mo HIV-free survival, estimated with survival analysis. In an individual-level analysis, we evaluated the effectiveness of various PMTCT regimens. In a community-level analysis, we evaluated the relationship between HIV-free survival and community PMTCT coverage (the proportion of HIV-exposed infants in each community that received any PMTCT intervention during gestation or breastfeeding). We also compared our community coverage results to those of a contemporaneous study conducted in the facilities serving each sampled community. Of 7,985 surveyed children under 2 y of age, 1,014 (12.7%) were HIV-exposed. Of these, 110 (10.9%) were HIV-infected, 851 (83.9%) were HIV-uninfected, and 53 (5.2%) were dead. HIV-free survival at 24 mo of age among all HIV-exposed children was 79.7% (95% CI: 76.4, 82.6) overall, with the following country-level estimates: Cameroon (72.6%; 95% CI: 62.3, 80.5), South Africa (77.7%; 95% CI: 72.5, 82.1), Zambia (83.1%; 95% CI: 78.4, 86.8), and Côte D'Ivoire (84.4%; 95% CI: 70.0, 92.2). In adjusted analyses, the risk of death or HIV infection was non-significantly lower in children whose mothers received a more complex regimen of either two or three antiretroviral drugs compared to those receiving no prophylaxis (adjusted hazard ratio: 0.60; 95% CI: 0.34, 1.06). Risk of death was not different for children whose mothers received a more complex regimen compared to those given single-dose nevirapine (adjusted hazard ratio: 0.88; 95% CI: 0.45, 1.72). Community PMTCT coverage was highest in Cameroon, where 75 of 114 HIV-exposed infants met criteria for coverage (66%; 95% CI: 56, 74), followed by Zambia (219 of 444, 49%; 95% CI: 45, 54), then South Africa (152 of 365, 42%; 95% CI: 37, 47), and then Côte D'Ivoire (3 of 53, 5.7%; 95% CI: 1.2, 16). In a cluster-level analysis, community PMTCT coverage was highly correlated with facility PMTCT coverage (Pearson's r = 0.85), and moderately correlated with 24-mo HIV-free survival (Pearson's r = 0.29). In 14 of 16 instances where both the facility and community samples were large enough for comparison, the facility-based coverage measure exceeded that observed in the community. CONCLUSIONS: HIV-free survival can be estimated with community surveys and should be incorporated into ongoing country monitoring. Facility-based coverage measures correlate with those derived from community sampling, but may overestimate population coverage. The more complex regimens recommended by the World Health Organization seem to have measurable public health benefit at the population level, but power was limited and additional field validation is needed.
Medication Side Effects and Retention in HIV Treatment: A Regression Discontinuity Study of Tenofovir Implementation in South Africa and Zambia.
(2018-Sep-01) Brennan AT; Bor J; Davies MA; Wandeler G; Prozesky H; Fatti G; Wood R; Stinson K; Tanser F; Bärnighausen T; Boulle A; Sikazwe I; Zanolini A; Fox MP; Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Research Department of Infection and Population Health, University College London, London, United Kingdom.; Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa.; Division of Public Health Medicine, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Institute of Public Health, School of Medicine, Heidelberg University, Heidelberg, Germany.; Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.; Department of Global Health, School of Public Health, Boston University, Boston, Massachusetts.; Kheth'Impilo AIDS Free Living, Cape Town, South Africa.; Division of Infectious Diseases, Department of Medicine, Tygerberg Academic Hospital, University of Stellenbosch, Cape Town, South Africa.; Africa Health Research Institute, Durban, South Africa.; The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Outcomes of Infants Starting Antiretroviral Therapy in Southern Africa, 2004-2012.
(2015-Aug-15) Porter M; Davies MA; Mapani MK; Rabie H; Phiri S; Nuttall J; Fairlie L; Technau KG; Stinson K; Wood R; Wellington M; Haas AD; Giddy J; Tanser F; Eley B; *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.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Treatment and outcome of AIDS-related Kaposi sarcoma in South Africa, Malawi and Zambia: an international comparison.
(2017) Rohner E; Kasaro M; Msadabwe-Chikuni SC; Stinson K; Mohamed Z; Tweya H; Egger M; Bohlius J; Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.; Radiation Oncology, Groote Schuur Hospital, Cape Town, South Africa.; Khayelitsha ART Program, Médecins Sans Frontières, Cape Town, South Africa.; Centre for Infectious Disease Epidemiology & Research, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa.; Cancer Diseases Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Lighthouse Trust at Kamuzu Central Hospital, Lilongwe, Malawi.
HIV-related Kaposi sarcoma (KS) is common in sub-Saharan Africa, but optimal treatment strategies in resource-limited settings remain unclear. We did a retrospective cohort study of adults diagnosed with KS before initiating antiretroviral therapy (ART) at three ART programs in South Africa, Malawi and Zambia. We extracted data from medical charts at HIV clinics and oncological referral centers and used electronic data from the International epidemiology Databases to Evaluate AIDS Southern Africa. We used descriptive statistics to assess tumor (T) and systemic illness (S) stage and treatment of AIDS-KS patients. Kaplan-Meier analyses were used to assess survival after KS diagnosis. We analyzed data from 57 patients in total (20 from South Africa, 20 from Zambia, 17 from Malawi). Median age at KS diagnosis was 35 years and similar across sites. The percentage of patients with poor risk AIDS-KS (T1S1) was similar in South Africa (25%) and Malawi (24%) and higher in Zambia (45%). All AIDS-KS patients initiated ART at the HIV clinic. For KS care, in South Africa 18 patients (90%) were referred to an oncology department; in Malawi and Zambia most patients were managed by the HIV clinics. In Malawi and South Africa, most AIDS-KS patients received systemic chemotherapy, in Zambia one patient received chemotherapy at the HIV clinic. A year after KS diagnosis, 15 patients (75%) in South Africa, 10 patients (50%) in Zambia, and 8 patients (47%) in Malawi were still alive; another 3 patients (15%) in South Africa, 8 patients (40%) in Zambia and 4 patients (24%) in Malawi were lost to follow-up. Management of AIDS-KS patients varied considerably across sites in Malawi, South Africa and Zambia. We need more reliable survival data for AIDS-KS patients in sub-Saharan Africa before we can assess which treatments and clinical pathways should be adopted in a specific setting.