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Mutumba M.,University of Michigan | Mutumba M.,Joint Clinical Research Center | Harper G.W.,University of Michigan
Journal of the International AIDS Society | Year: 2015

Introduction: The patterning of the HIV epidemic within young key populations (YKPs) highlights disproportionate burden by mental disorders in these populations. The mental wellbeing of YKPs is closely associated with biological predispositions and psychosocial factors related to YKPs' sexual and gender identities and socio-economic status. The purpose of this paper is to highlight sources of risk and resilience, as well as identify treatment and supports for mental health disorders (MHDs) among YKPs. Discussion: This paper utilizes Bronfenbrenner's Bioecological Systems Theory and the Social Stress Model to explore the risk and protective factors for MHDs across YKPs' ecological systems, and identify current gaps in treatment and support for MHDs among these youth. We emphasize the fluidity and intersections across these categorizations which reinforce the vulnerability of these populations, the lack of concrete data to inform mental health interventions among YKPs, and the need to ground YKP interventions and programmes with human rights principles stipulated in the convention on the rights of a child. Conclusions: We put forth recommendations for future research and strategies to address the mental wellbeing of YKPs, including the need for integrated interventions that address the multiplicity of risk factors inherent in the multiple group membership, rather than single-focus interventions whilst addressing the unique needs or challenges of YKPs. © 2015 Mutumba M and Harper GW ; licensee International AIDS Society.

Palar K.,University of California at Los Angeles | Palar K.,RAND Corporation | Wagner G.,RAND Corporation | Ghosh-Dastidar B.,RAND Corporation | Mugyenyi P.,Joint Clinical Research Center
AIDS | Year: 2012

Objective: Although the physical health benefits of HIV antiretroviral therapy (ART) are well documented, the socioeconomic benefits are still being established. Few studies have examined the effects of ART on food insecurity, although studies suggest there may be a benefit via improved health and ability to work. Design: Twelve-month prospective cohort study of 602 treatment-naive patients initiating clinical care in Uganda. Methods: Longitudinal multivariate logistic regression was used to investigate the effect of ART on food insecurity compared to HIV care without ART. A staged regression approach was used to explore pathways through which ART may affect food insecurity. Results: Food insecurity decreased significantly for both the ART and non-ART groups over time, with the ART group experiencing greater reductions by the end of the study. ART remained a significant predictor of reduction in food insecurity over time after controlling for baseline differences in the regression model (odds ratio 0.642; P < 0.01). Improvements in work and mental health status were identified as potential pathways through which ART may improve food security. Conclusion: Taken together with the well known benefits of food security on ART adherence, treatment retention and clinical outcomes in resource-poor settings, our results suggest that a positive feedback loop of improved functioning and productivity could result from the interaction between food security and ART. Policymakers could leverage this positive cycle by strengthening mental health support and promoting sustainable food security interventions as part of HIV treatment programs. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Hamers R.L.,University of Amsterdam | Schuurman R.,University Utrecht | Sigaloff K.C.E.,University of Amsterdam | Wallis C.L.,University of Witwatersrand | And 11 more authors.
The Lancet Infectious Diseases | Year: 2012

Background: The effect of pretreatment HIV-1 drug resistance on the response to first-line combination antiretroviral therapy (ART) in sub-Saharan Africa has not been assessed. We studied pretreatment drug resistance and virological, immunological, and drug-resistance treatment outcomes in a large prospective cohort. Methods: HIV-1 infected patients in the PharmAccess African Studies to Evaluate Resistance Monitoring (PASER-M) cohort started non-nucleoside reverse transcriptase inhibitor-based ART at 13 clinical sites in six countries, from 2007 to 2009. We used the International Antiviral Society-USA drug resistance mutation list and the Stanford algorithm to classify participants into three pretreatment drug resistance categories: no pretreatment drug resistance, pretreatment drug resistance with fully active ART prescribed, or pretreatment drug resistance with reduced susceptibility to at least one prescribed drug. We assessed risk factors of virological failure (≥400 copies per mL) and acquired drug resistance after 12 months of ART by use of multilevel logistic regression with multiple imputations for missing data. CD4 cell count increase was estimated with linear mixed models. Findings: Pretreatment drug resistance results were available for 2579 (94%) of 2733 participants; 2404 (93%) had no pretreatment drug resistance, 123 (5%) had pretreatment drug resistance to at least one prescribed drug, and 52 (2%) had pretreatment drug resistance and received fully active ART. Compared with participants without pretreatment drug resistance, the odds ratio (OR) for virological failure (OR 2·13, 95% CI 1·44-3·14; p<0·0001) and acquired drug-resistance (2·30, 1·55-3·40; p<0·0001) was increased in participants with pretreatment drug resistance to at least one prescribed drug, but not in those with pretreatment drug resistance and fully active ART. CD4 count increased less in participants with pretreatment drug resistance than in those without (35 cells per μL difference after 12 months; 95% CI 13-58; p=0·002). Interpretation: At least three fully active antiretroviral drugs are needed to ensure an optimum response to first-line regimens and to prevent acquisition of drug resistance. Improved access to alternative combinations of antiretroviral drugs in sub-Saharan Africa is warranted. Funding: The Netherlands Ministry of Foreign Affairs. © 2012 Elsevier Ltd.

Kenny J.,Medical Research Council | Kenny J.,University College London | Musiime V.,Joint Clinical Research Center | Judd A.,Medical Research Council | Gibb D.,Medical Research Council
Current Opinion in HIV and AIDS | Year: 2012

PURPOSE OF REVIEW: Antiretroviral therapy (ART) has greatly improved the survival of HIV-infected children. However, ART is associated with immediate and long-term adverse events. Pharmacovigilance systems, although imperfect, have been developed in many high-income countries (HICs), but coverage in low-and middle-income countries (LMICs) is poor and uneven. This review covers the recent advances in the understanding of adverse events following perinatal ART exposure, including surveillance from birth cohorts; we also describe the adverse events of antiretroviral drugs among HIV-infected children, focussing particularly on those relevant to LMICs, where more than 90% of HIV-infected children live. RECENT FINDINGS: ART is largely safe in both HIV-infected and HIV-exposed uninfected children, in whom no significant increase in birth defects has been noted. Among HIV-infected children, toxicity to some drugs may be less frequent than in adults, possibly related to immature immune systems in younger children. As per WHO guidelines, many countries are moving from stavudine-based to zidovudine-based or abacavir-based fixed-dose combination (with nevirapine/lamivudine) paediatric mini-pills. However, reassuring data are emerging about short-term stavudine use in LMICs, as this remains an important first-line regimen for young children, as well as an alternative to zidovudine for anaemic children. Zidovudine appears to be well tolerated in young children living in nonmalarious areas, and, among African children, concerns about abacavir hypersensitivity have not been substantiated. SUMMARY: Optimization of first-line ART regimens needs to take account of the toxicities in HIV-infected children, in particular as they will take ART much longer than adults and during the period of growth and development. The benefits of ART in pregnancy are clear, but long-term follow-up of ART-exposed infants in LMICs through integrated surveillance systems would be invaluable. Copyright © Lippincott Williams & Wilkins.

Orikiiriza J.,Makerere University | Bakeera-Kitaka S.,Makerere University | Musiime V.,Joint Clinical Research Center | Mworozi E.A.,Makerere University | And 2 more authors.
AIDS | Year: 2010

Objective: To determine clinical pattern, prevalence, and factors associated with pediatric immune reconstitution inflammatory syndrome (IRIS) in Uganda. DESIGN: A prospective, multicenter cross-sectional study. Methods: We enrolled HIV-infected children receiving antiretroviral therapy (ART) between 0.5 and 6 months duration from December 2006 to October 2007 at three pediatric clinics in Uganda. Children were evaluated for IRIS at a one-time study visit by a standardized pediatric case definition. Results: The IRIS prevalence was 38% [95% confidence interval (CI) 31-46] among 162 children (57% female) with a median age of 6 years (interquartile range 2.5-11 years). Of the IRIS events, 77% were unmasking of a new opportunistic infection and 23% were probable paradoxical IRIS events toward prior opportunistic infections. The majority of IRIS events (55%) occurred in the first month of ART. The clinical events were diverse, with tuberculosis-IRIS (29%) being the most frequent presentation. Independent risk factors for IRIS were pre-ART CD4 cell percentage below 15% (odds ratio = 3.1, 95% CI 1.2-8.4, P = 0.027), current CD8 cell absolute count below 1000 cells/μl (odds ratio = 4.3, 95% CI 1.8-10.4, P = 0.001), male sex (odds ratio = 2.6, 95% CI 1.06-8.4, P = 0.01), and a cough of more than 1 week duration at the current clinic visit (odds ratio = 4.3, 95% CI 1.7-10.7, P = 0.002). A more than 25 CD4 T-cells increase at current study visit from the pre-ART baseline was associated with IRIS by univariate (P = 0.005) but not multivariate analysis. Conclusion: IRIS events commonly occur early after ART initiation in children with advanced immunosuppression, as commonly seen in resource-limited areas. Both healthcare providers and caregivers of the children need awareness of IRIS to minimize ART nonadherence. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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