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      Factors Associated with Treatment Outcomes Among Children and Adolescents Living with HIV Receiving Antiretroviral Therapy in Central Kenya

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          Abstract

          Expanded access to HIV treatment services has improved outcomes for children and adolescents living with HIV in Kenya. Minimal data are available on these outcomes. We describe temporal trends in outcomes for children and adolescents initiating antiretroviral therapy (ART) from 2004 to 2014 at sites supported by Centre for Health Solutions—Kenya, in central Kenya. We retrospectively analyzed data from children 0–9 years of age ( n = 3,519) and adolescents 10–19 years of age ( n = 1,663) living with HIV, who newly initiated ART at 47 health facilities in central Kenya. Year cohorts were analyzed from the Comprehensive Patient Application Database (CPAD) and International Quality Care (IQCare) electronic medical databases, including temporal trends in outcomes and associated factors using multivariable competing risk regression analysis. There were more girls (2,453 [52.7%]) than boys, with most enrolled at World Health Organization (WHO) stage II (1,813 [37.7%]) or III disease (1,694 [35.1%]). Most of the children and adolescents (4,431 [96.4%]) did not have tuberculosis (TB) symptoms. Cumulative lost to follow-up (LTFU) incidence at 6, 12, 24, and 36 months were 5.0%, 9.9%, 22.9%, and 33.1%, respectively. Cumulative mortality incidence at 6, 12, 24, and 36 months were 0.7%, 1.0%, 1.2%, and 1.5%, respectively. The incidence of LTFU was higher among female children and adolescents, those initiated on tenofovir-based regimens, and those with presumptive TB symptoms. Mortality risk was higher among those with WHO stage III or IV disease, and children and adolescents on TB treatment or who had presumptive TB. Enrollment occurred at a young age and pediatric-friendly ART regimens were initiated at earlier WHO stages implying effective early infant diagnosis and treatment for all strategies, resulting in improved treatment outcomes. The higher retention rates in recent years as well as the lower retention after many years of follow-up underscore the importance of implementing longitudinal follow-up strategies targeting this population.

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          Estimation of failure probabilities in the presence of competing risks: new representations of old estimators.

          A topic that has received attention in both the statistical and medical literature is the estimation of the probability of failure for endpoints that are subject to competing risks. Despite this, it is not uncommon to see the complement of the Kaplan-Meier estimate used in this setting and interpreted as the probability of failure. If one desires an estimate that can be interpreted in this way, however, the cumulative incidence estimate is the appropriate tool to use in such situations. We believe the more commonly seen representations of the Kaplan-Meier estimate and the cumulative incidence estimate do not lend themselves to easy explanation and understanding of this interpretation. We present, therefore, a representation of each estimate in a manner not ordinarily seen, each representation utilizing the concept of censored observations being 'redistributed to the right.' We feel these allow a more intuitive understanding of each estimate and therefore an appreciation of why the Kaplan-Meier method is inappropriate for estimation purposes in the presence of competing risks, while the cumulative incidence estimate is appropriate.
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            Effects of undernutrition on mortality and morbidity among adults living with HIV in sub-Saharan Africa: a systematic review and meta-analysis

            Background Undernutrition is one of the most common problems among people living with HIV, contributing to premature death and the development of comorbidities within this population. In Sub-Saharan Africa (SSA), the impacts of these often inter-related conditions appear in a series of fragmented and inconclusive studies. Thus, this review examines the pooled effects of undernutrition on mortality and morbidities among adults living with HIV in SSA. Methods A systematic literature search was conducted from PubMed, EMBASE, CINAHL, and Scopus databases. All observational studies reporting the effects of undernutrition on mortality and morbidity among adults living with HIV in SSA were included. Heterogeneity between the included studies was assessed using the Cochrane Q-test and I2 statistics. Publication bias was assessed using Egger’s and Begg’s tests at a 5% significance level. Finally, a random-effects meta-analysis model was employed to estimate the overall adjusted hazard ratio. Results Of 4309 identified studies, 53 articles met the inclusion criteria and were included in this review. Of these, 40 studies were available for the meta-analysis. A meta-analysis of 23 cohort studies indicated that undernutrition significantly (AHR: 2.1, 95% CI: 1.8, 2.4) increased the risk of mortality among adults living with HIV, while severely undernourished adults living with HIV were at higher risk of death (AHR: 2.3, 95% CI: 1.9, 2.8) as compared to mildly undernourished adults living with HIV. Furthermore, the pooled estimates of ten cohort studies revealed that undernutrition significantly increased the risk of developing tuberculosis (AHR: 2.1, 95% CI: 1.6, 2.7) among adults living with HIV. Conclusion This review found that undernutrition has significant effects on mortality and morbidity among adults living with HIV. As the degree of undernutrition became more severe, mortality rate also increased. Therefore, findings from this review may be used to update the nutritional guidelines used for the management of PLHIV by different stakeholders, especially in limited-resource settings. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-020-05706-z.
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              Practical methods for competing risks data: a review.

              Competing risks data arise naturally in medical research, when subjects under study are at risk of more than one mutually exclusive event such as death from different causes. The competing risks framework also includes settings where different possible events are not mutually exclusive but the interest lies on the first occurring event. For example, in HIV studies where seropositive subjects are receiving highly active antiretroviral therapy (HAART), treatment interruption and switching to a new HAART regimen act as competing risks for the first major change in HAART. This article introduces competing risks data and critically reviews the widely used statistical methods for estimation and modelling of the basic (estimable) quantities of interest. We discuss the increasingly popular Fine and Gray model for subdistribution hazard of interest, which can be readily fitted using standard software under the assumption of administrative censoring. We present a simulation study, which explores the robustness of inference for the subdistribution hazard to the assumption of administrative censoring. This shows a range of scenarios within which the strictly incorrect assumption of administrative censoring has a relatively small effect on parameter estimates and confidence interval coverage. The methods are illustrated using data from HIV-1 seropositive patients from the collaborative multicentre study CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe).
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                Author and article information

                Journal
                AIDS Res Hum Retroviruses
                AIDS Res Hum Retroviruses
                aid
                AIDS Research and Human Retroviruses
                Mary Ann Liebert, Inc., publishers (140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA )
                0889-2229
                1931-8405
                June 2022
                06 June 2022
                06 June 2022
                : 38
                : 6
                : 480-490
                Affiliations
                [ 1 ]Centre for Health Solutions—Kenya (CHS), Nairobi, Kenya.
                [ 2 ]Division of Global HIV and TB, Centers for Disease Control and Prevention, Nairobi, Kenya.
                Author notes
                [*]Address correspondence to: Paul Wekesa, Centre for Health Solutions—Kenya (CHS), CVS Plaza, Kasuku Road, Off Lenana Road, P.O. Box 23248-00100, Nairobi, Kenya pwekesa@ 123456chskenya.org
                Author information
                https://orcid.org/0000-0001-9274-7731
                Article
                10.1089/aid.2021.0112
                10.1089/aid.2021.0112
                9225829
                35229643
                524ffc67-3d67-4515-bcd6-be986d4d2e10
                © Angela McLigeyo et al. 2022; Published by Mary Ann Liebert, Inc.

                This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 5, Tables: 5, References: 38, Pages: 11
                Product
                Categories
                Outcomes Research

                adolescents,antiretroviral therapy,hiv positive,kenya,pediatric,treatment outcomes

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