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Geneva, Switzerland, WHO, 2009.  p.As part of efforts to obtain evidence to inform the public health approach to HIV treatment and prevention, the Population Council collaborated with the HIV / AIDS Department of the World Health Organization to develop tools, "HIV Testing, Treatment and Prevention: Generic Tools for Operational Research" for operational research on topics that have relevance to programs. The tools include this main document that is intended to serve as a basis for formulating research questions and designing an operational research project to address them. The document includes four sections: HIV testing and counseling; HIV stigma and discrimination; Adherence to antiretrovirals; and HIV prevention in the context of scaled-up access to HIV treatment.
Geneva, Switzerland, WHO, 2009 Nov. 25 p.Based on the latest scientific evidence, the World Health Organization (WHO) has released new recommendations on HIV treatment and prevention and infant feeding in the context of HIV. WHO now recommends earlier initiation of antiretroviral therapy for adults and adolescents, the delivery of more patient-friendly antiretroviral drugs (ARVs), and prolonged use of ARVs to reduce the risk of mother-to-child transmission of HIV. For the first time, WHO recommends that HIV-positive mothers or their infants take ARVs while breastfeeding to prevent HIV transmission.
Indian Journal of Pediatrics. 2009 Oct; 76(10):1017-21.OBJECTIVE: To assess the metabolic drug toxicities of first-line, World Health Organization (WHO)-recommended generic highly active antiretroviral therapy (HAART) regimens, to estimate the prevalence of body fat redistribution and to identify associated risk factors. METHODS: Cross-sectional observational study. During 3 month period, 52 HIV infected children (25 on HAART; 27 not on HAART) were assessed. Their sociodemographic, clinical, and immunological data was recorded. Children were examined or the signs of fat redistribution (peripheral lipoatrophy and central lipohypertrophy). Liver function tests, fasting blood sugar, lipid profile, serum amylase, serum lactate, blood pH and bicarbonate levels were done in all patients. RESULTS: Twenty-two patients were on stavudine and three on zidovudine based HAART. None of the patients ever received any protease inhibitor. There were no cases of clinical or immunological failure. Children on HAART had significantly lower weight for age and body mass index but the mean height for age was similar between study groups. Only two cases of peripheral lipoatrophy were observed. Hypercholesterolemia was observed in four children on HAART but none without therapy. Hypertriglyceridemia was observed in three children on HAART and seven without therapy. Four cases of asymptomatic mild hyperlactatemia were observed. No case of any hyperglycemia or liver impairment was observed. CONCLUSION: Metabolic abnormalities and lipodystrophy are emerging complications of HAART in Indian children and needs very close follow up. Future studies with larger sample size and longitudinal model are recommended.
Comparison of previous and present World Health Organization clinical staging criteria in HIV-infected Malawian children.
AIDS. 2009 Sep 10; 23(14):1913-6.In many settings, HIV infected children are looked after with limited access to CD4 cell count or viral load. The decision to initiate antiretroviral therapy (ART) is made clinically, based on the WHO paediatric staging criteria, which were revised in 2006. Results of using new and old criteria were compared. Of 694 children, 626 (90.2%) fulfilled criteria to start ART when applying the new WHO staging guidelines, whereas 330 (47.6%) children were eligible for ART when using the old WHO criteria. This signifies a marked rise in the number of paediatric patients qualifying for ART on clinical grounds.
Arlington, Virginia, John Snow [JSI], AIDS Support and Technical Assistance Resources [AIDSTAR-One], 2009 Mar. 23 p. (USAID Contract No. GHH-I-00-07-00059-00; AIDSTAR-One Technical Brief)This brief describes WHO recommendations and provides links to useful resources for HIV / AIDS program implementers.
A practical guide to integrating reproductive health and HIV / AIDS into grant proposals to the Global Fund.
[Washington, D.C.], Population Action International, 2009 Sep. 61 p.Starting in recent proposal rounds, The Global Fund for AIDS, Tuberculosis and Malaria (GFATM) has stated more explicitly that countries can include reproductive health as part of their proposals on AIDS, tuberculosis and malaria, as long as a justification is provided on the impact of reproductive health (RH) on reducing one of the three diseases. This document is for countries and organizations, including CCMs, government and nongovernmental organizations and civil society organizations, to help in integrating reproductive health, including family planning (RH) and HIV / AIDS in proposals submitted to the Global Fund. The document takes a country approach to integration since the Global Fund seeks to support proposals that build on and strengthen national programs. (Excerpt)
Journal of Acquired Immune Deficiency Syndromes. 2009 Sep 1; 52(1):106-13.BACKGROUND: Current World Health Organization (WHO) guidelines for treatment of HIV in resource-limited settings call for 2 antiretroviral regimens. The effectiveness and cost-effectiveness of increasing the number of antiretroviral regimens is unknown. METHODS: Using a simulation model, we compared the survival and costs of current WHO regimens with two 3-regimen strategies: an initial regimen of 3 nucleoside reverse transcriptase inhibitors followed by the WHO regimens and the WHO regimens followed by a regimen with a second-generation boosted protease inhibitor (2bPI). We evaluated monitoring with CD4 counts only and with both CD4 counts and viral load. We used cost and effectiveness data from Cape Town and tested all assumptions in sensitivity analyses. RESULTS: Over the lifetime of the cohort, 25.6% of individuals failed both WHO regimens by virologic criteria. However, when patients were monitored using CD4 counts alone, only 6.5% were prescribed additional highly active antiretroviral therapy due to missed and delayed detection of failure. The life expectancy gain for individuals who took a 2bPI was 6.7-8.9 months, depending on the monitoring strategy. When CD4 alone was available, adding a regimen with a 2bPI was associated with an incremental cost-effectiveness ratio of $2581 per year of life gained, and when viral load was available, the ratio was $6519 per year of life gained. Strategies with triple-nucleoside reverse transcriptase inhibitor regimens in initial therapy were dominated. Results were sensitive to the price of 2bPIs. CONCLUSIONS: About 1 in 4 individuals who start highly active antiretroviral therapy in sub-Saharan Africa will fail currently recommended regimens. At current prices, adding a regimen with a 2bPI is cost effective for South Africa and other middle-income countries by WHO standards.
Expert Opinion On Pharmacotherapy. 2009 Aug; 10(11):1783-91.BACKGROUND: Treating HIV-infected children remains a challenge due to a lack of treatment options, appropriate drug formulations and, in countries with limited resources, insufficient access to diagnostic tests and treatment. OBJECTIVE: To summarize current data concerning new opportunities to improve the treatment of HIV-infected children. METHODS: This review includes data from the most recently published peer-reviewed publications, guidelines or presentations at international meetings concerning new ways to treat HIV-infected children. RESULTS/CONCLUSIONS: New WHO guidelines recommend starting combination antiretroviral treatment in all infants aged < 1 year. Although this is common practice in some high-income countries, implementation of these recommendations in countries with limited resources is still a challenge. There is still an important gap between the availability of licensed drugs in children compared with adults. There remains a need for further pharmacokinetic studies, and for more pediatric formulations of antiretroviral drugs with improved palatability.
Total lymphocyte count and World Health Organization pediatric clinical stage as markers to assess need to initiate antiretroviral therapy among human immunodeficiency virus-infected children in Moshi, Northern Tanzania.
Pediatric Infectious Disease Journal. 2009 Jun; 28(6):493-7.BACKGROUND: The World Health Organization (WHO) has recommended the use of clinical staging alone and with total lymphocyte count to identify HIV infected children in need of antiretroviral therapy (ART) in resource-limited settings, when CD4 cell count is not available.METHODS: We prospectively enrolled children obtaining care for HIV infection at the Kilimanjaro Christian Medical Centre Pediatric Infectious Diseases Clinic in Moshi, Tanzania between March 2004 and May 2006 for this cohort study.RESULTS: One hundred ninety two (89.7%) of 214 children met WHO ART initiation criteria based on clinical staging or CD4 cell count. Several low-cost measures identified individuals who met WHO ART initiation criteria to the following degree: WHO stages 3 or 4 had 87.5% (95% CI, 82.8-92.1) sensitivity and, by definition, 100% (CI, 100-100) specificity; WHO recommended advance disease TLC cutoffs: sensitivity = 23.9% (95% CI, 17.3-30.5) specificity = 78.2% (95% CI, 67.3-89.1). Low TLC was a common finding, (50 of 214; 23%); however, it did not improve the sensitivity or specificity of clinical staging in identifying the severely immunosuppressed stage 2 children. Growth failure or use of total lymphocyte counts in isolation were not reliable indicators of severe immunosuppression or need to initiate ART.CONCLUSION: The use of total lymphocyte count does not improve the ability to identify children in need of ART compared with clinical staging alone. Low absolute lymphocyte count did not correlate with severe immunosuppression based on CD4 cell count in this cohort.
Antiretroviral resistance patterns and HIV-1 subtype in mother-infant pairs after the administration of combination short-course zidovudine plus single-dose nevirapine for the prevention of mother-to-child transmission of HIV.
Clinical Infectious Diseases. 2009 Jul 15; 49(2):299-305.BACKGROUND: World Health Organization guidelines for prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) recommend administration of zidovudine and single-dose nevirapine (NVP) for HIV-1-infected women who are not receiving treatment for their own health or if complex regimens are not available. This study assessed antiretroviral resistance patterns among HIV-infected women and infants receiving single-dose NVP in Thailand, where the predominant circulating HIV-1 strains are CRF01_AE recombinants and where the minority are subtype B. METHODS: Venous blood samples were obtained from (1) HIV-infected women who received zidovudine from 34 weeks' gestation and single-dose NVP plus oral zidovudine during labor and (2) HIV-infected infants who received single-dose NVP after birth plus zidovudine for 4 weeks after delivery. HIV-1 drug resistance testing was performed using the TruGene assay (Bayer HealthCare). RESULTS: Most mothers and infants were infected with CRF01_AE. NVP resistance was detected in 34 (18%) of 190 women and 2 (20%) of 10 infants. There was a significantly higher proportion of NVP mutations in women with delivery viral loads of >50,000 copies/mL (adjusted odds ratio, 8.5; 95% confidence interval, 2.2-32.8, [Formula: see text] for linear trend) and in those with subtype B rather than CRF01_AE infections (38% vs. 16%; adjusted odds ratio, 3.6; 95% confidence interval, 1.1-11.8; P = .038). CONCLUSIONS: The lower frequency of NVP mutations among mothers infected with subtype CRF01_AE, compared with mothers infected with subtype B, suggests that individuals infected with subtype CRF01_AE may be less susceptible to the induction of NVP resistance than are individuals infected with subtype B.
Validation of 2006 WHO prediction scores for true HIV infection in children less than 18 months with a positive serological HIV test.
PloS One. 2009; 4(4):e5312.INTRODUCTION: All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system. METHODS AND RESULTS: From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%. CONCLUSION: As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition.
Current Opinion In HIV and AIDS. 2009 May; 4(3):222-31.PURPOSE OF REVIEW: We review the current literature supporting adoption of higher CD4 thresholds for initiation of antiretroviral treatment and survey progress in adoption of early treatment policies in resource-limited settings. We highlight some of the challenges and opportunities implementation of early treatment will bring. RECENT FINDINGS: The initial success of combination antiretroviral treatment resulted in the recommendation to treat early all individuals with HIV. However, the gradual realization that antiretroviral treatment was associated with toxicity led to a more tempered approach. Recent cohort studies and some clinical trials have shown that delaying treatment is associated with increased morbidity and mortality. SUMMARY: Early treatment is routinely practiced in developed countries. Now, early treatment is being adopted as a strategy in many resource-limited settings. The implications of this policy shift are not known, but we predict early treatment will have important consequences for the health system, the individual, and the community. Whereas these consequences will bring significant challenges, the increased numbers of HIV-infected individuals on treatment will result in many new opportunities - antiretroviral treatment will become less expensive, systems to deliver chronic care will be strengthened, and the policy shift will focus greater attention on pregnant women and children. Finally, some authors postulate that early treatment may impact HIV transmission.
Low levels of antiretroviral-resistant HIV infection in a routine clinic in Cameroon that uses the World Health Organization (WHO) public health approach to monitor antiretroviral treatment and adequacy with the WHO recommendation for second-line treatment.
Clinical Infectious Diseases. 2009 May 1; 48(9):1318-22.A cross-sectional study, performed at a routine human immunodeficiency virus (HIV)/AIDS clinic in Cameroon that uses the World Health Organization public health approach, showed low rates of virological failure and drug resistance at 12 and 24 months after initiation of antiretroviral therapy. Importantly, the cross-sectional study also showed that the World Health Organization recommendation for second-line treatment would be effective in almost all patients with HIV drug resistance mutations.