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IntroductionHIV‐positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose‐associated disorders among HIV‐positive patients have been reported to range between 2 and 14%, and in an ageing HIV‐positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short‐term (six‐month) risk of DM in HIV‐positive populations and to compare the existing models developed in the general population.MethodsAll patients recruited to the Data Collection on Adverse events of Anti‐HIV Drugs (D:A:D) study with follow‐up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV‐related factors were assessed using Poisson‐regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal‐external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined.ResultsOf 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person‐years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV‐related factors, recent CD4 counts of<200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over‐predicted DM events compared to D:A:D for lower glucose and lower triglycerides, and for BMI levels below 25 kg/m2.ConclusionsThe D:A:D equation performed well in predicting the short‐term onset of DM in the validation dataset and for specific subgroups provided better estimates of DM risk than the Framingham.

ABSTRACT OBJECTIVE To analyze Government strategies for reducing prices of antiretroviral medicines for HIV in Brazil. METHODS Analysis of Ministry of Health purchases of antiretroviral medicines, from 2005 to 2013. Expenditures and costs of the treatment per year were analyzed and compared to international prices of atazanavir. Price reductions were estimated based on the terms of a voluntary license of patent rights and technology transfer in the Partnership for Productive Development Agreement for atazanavir. RESULTS Atazanavir, a patented medicine, represented a significant share of the expenditures on antiretrovirals purchased from the private sector. Prices in Brazil were higher than international references, and no evidence was found of a relationship between purchase volume and price paid by the Ministry of Health. Concerning the latest strategy to reduce prices, involving local production of the 200 mg capsule, the price reduction was greater than the estimated reduction. As for the 300 mg capsule, the amounts paid in the first two years after the Partnership for Productive Development Agreement were close to the estimated values. Prices in nominal values for both dosage forms remained virtually constant between 2011 (the signature of the Partnership for Productive Development Agreement), 2012 and 2013 (after the establishment of the Partnership). CONCLUSIONS Price reduction of medicines is complex in limited-competition environments. The use of a Partnership for Productive Development Agreement as a strategy to increase the capacity of local production and to reduce prices raises issues regarding its effectiveness in reducing prices and to overcome patent barriers. Investments in research and development that can stimulate technological accumulation should be considered by the Government to strengthen its bargaining power to negotiate medicines prices under a monopoly situation. ; RESUMO OBJETIVO Analisar as estratégias governamentais para redução de preço de medicamentos antirretrovirais para aids no Brasil. MÉTODOS Realizada análise das compras de medicamentos antirretrovirais pelo Ministério da Saúde, de 2005 a 2013. Foram analisados o gasto e o custo do tratamento por ano e comparados com os preços internacionais para o atazanavir. Foram estimadas as reduções com base no contrato da Parceria para Desenvolvimento Produtivo para obtenção de licença voluntária de patente e transferência de tecnologia do atazanavir. RESULTADOS O atazanavir teve peso expressivo nos gastos com antirretrovirais adquiridos no setor privado. Os preços praticados no Brasil foram mais altos que aqueles de referência internacional e não houve evidências da relação entre volume de compra e preço pago pelo Ministério da Saúde, por ser medicamento patenteado. Em relação à estratégia mais recente para reduzir preços, envolvendo produção local da cápsula de 200 mg, as reduções foram menores do que as estimadas. Quanto à cápsula de 300 mg, os valores pagos nos dois primeiros anos após a Parceria para Desenvolvimento Produtivo foram próximos aos estimados. Os preços em valores nominais mantiveram-se praticamente constantes entre 2011 (assinatura da Parceria para Desenvolvimento Produtivo), 2012 e 2013 (após estabelecida a Parceria). CONCLUSÕES A redução do preço de medicamentos é complexa em ambiente de concorrência limitada. O uso da Parceria para Desenvolvimento Produtivo como método para aumentar a capacidade de produção local e reduzir preços levanta questões em relação à redução efetiva dos preços e ao enfrentamento da barreira patentária. Investimentos em pesquisa e desenvolvimento que possam estimular a acumulação tecnológica devem ser considerados pelo governo para fortalecer seu poder de barganha ao negociar preços de medicamentos em situação de monopólio.

BACKGROUND: The growing burden of the HIV and non-communicable disease (NCD) syndemic in Sub- Saharan Africa has necessitated introduction of integrated models of care in order to leverage existing HIV care infrastructure for NCDs. However, there is paucity of literature on treatment outcomes for multimorbid patients attending integrated care. We describe 12-month treatment outcomes among multimorbid patients attending integrated antiretroviral treatment (ART) and NCD clubs in Cape Town, South Africa. METHODS: As part of an integrated clubs (IC) model pilot implemented in 2016 by the local government at two primary health care clinics in Cape Town, we identified all multimorbid patients who were enrolled for IC for at least 12 months by August 2017. Mean adherence percentages (using proxy of medication collection and attendance of club visits) and optimal disease control (defined as the proportion of participants achieving optimal blood pressure, glycosylated haemoglobin control and HIV viral load suppression where appropriate) were calculated at 12 months before, at the point of IC enrolment and 12 months after IC enrolment. Predictors of NCD control 12 months post IC enrolment were investigated using multivariable logistic regression. RESULTS: As of 31 August 2017, 247 HIV-infected patients in total had been enrolled into IC for at least 12 months. Of these, 221 (89.5%) had hypertension, 4 (1.6%) had diabetes mellitus and 22 (8.9%) had both diseases. Adherence was maintained before and after IC enrolment with mean adherence percentages of 92.2% and 94.2% respectively. HIV viral suppression rates were 98.6%, 99.5% and 99.4% at the three time points respectively. Retention in care was high with 6.9% lost to follow up at 12 months post IC enrolment. Across the 3 time-points, optimal blood pressure control was achieved in 43.1%, 58.9% and 49.4% of participants while optimal glycaemic control was achieved in 47.4%, 87.5% and 53.3% of participants with diabetes respectively. Multivariable logistic analyses showed no independent variables significantly associated with NCD control. CONCLUSION: Multimorbid adults living with HIV achieved high levels of HIV control in integrated HIV and NCD clubs. However, intensified interventions are needed to maintain NCD control in the long term.

BACKGROUND: Highly active anti-retroviral therapy (HAART) prolongs the life span of people living with HIV (PLWHIV) and intensely reduces HIV-related morbidity and mortality. Globally, HIV-associated non-communicable diseases are becoming major public concerns, and chronic comorbidities have appeared as a substantial reason for morbidity and mortality in HIV patients with prolonged use of HAART. PURPOSE: A cross-sectional study design was used to assess the magnitude of diabetes mellitus and risk factors among adult HIV patients exposed to HAART at Jimma Zone Public Hospitals from May to July 30, 2018. PATIENTS AND METHODS: A convenient sampling technique was used to include a total of 271 adult HIV patients on HAART visiting the selected health facilities at the time of data collection. Socio-demographic and clinical data were collected by interviewer-administered questionnaire and by reviewing patients' record data. Bivariate and multivariate logistic regressions were used to identify variables that are independent predictors for diabetes mellitus. RESULTS: The prevalence of diabetes and pre-diabetes among PLWHIV exposed to HAART was 11.4% and 16.6%, respectively. The prevalence of diabetic dyslipidemia in PLWHIV exposed on HAART was 8.9% (n=24). Government workers (AOR: 0.17, 95% C.I=0.03–0.85, P=0.031), long duration in HAART use (AOR: 11.06, 95% C.I:1.03–18.67, P=0.047), hyper-triglyceridemia (AOR: 2.62,95% C.I:0.82, 8.39, P=0.005), LDL-C <130 mg/dl (AOR: 4.04, 95% C.I=1.33–12.30, P=0.014), and obesity (AOR: 9.62, 95% C.I: 1.01–91.52, P=0.049) were independent risk factors for diabetes mellitus in PLWHIV exposed to HAART. CONCLUSION: Exposure to HAART increased the prevalence of diabetes mellitus in PLWHIV although it enhances quality of life, improves immune functions and prevents the onset of opportunistic infections. Therefore, regular screening for blood glucose level for PLWHIV on HAART is advisable.

Passing through the blood-brain barrier (BBB) to treat neurological conditions is one of the main hurdles in modern medicine. Many drugs with promising in vitro profiles become ineffective in vivo due to BBB restrictive permeability. In particular, this includes drugs such as antiviral porphyrins, with the ability to fight brain-resident viruses causing diseases such as HIV-associated neurocognitive disorders (HAND). In the last two decades, BBB shuttles, particularly peptide-based ones, have shown promise in carrying various payloads across the BBB. Thus, peptide-drug conjugates (PDCs) formed by covalent attachment of a BBB peptide shuttle and an antiviral drug may become key therapeutic tools in treating neurological disorders of viral origin. In this study, we have used various approaches (guanidinium, phosphonium, and carbodiimide-based couplings) for on-resin synthesis of new peptide-porphyrin conjugates (PPCs) with BBB-crossing and potential antiviral activity. After careful fine-tuning of the synthetic chemistry, DIC/oxyma has emerged as a preferred method, by which 14 different PPCs have been made and satisfactorily characterized. The PPCs are prepared by coupling a porphyrin carboxyl group to an amino group (either N-terminal or a Lys side chain) of the peptide shuttle and show effective in vitro BBB translocation ability, low cytotoxicity toward mouse brain endothelial cells, and low hemolytic activity. Three of the PPCs, MP-P5, P4-MP, and P4-L-MP, effectively inhibiting HIV infectivity in vitro, stand out as most promising. Their efficacy against other brain-targeting viruses (Dengue, Zika, and SARS-CoV-2) is currently under evaluation, with preliminary results confirming that PPCs are a promising strategy to treat viral brain infections. ; Work supported by the La Caixa Health Foundation (project HR17_00409, ID 100010434, agreement LCF/PR/HR17/52150011), by the European Union (H2020-FETOPEN-2018-2019-2020-01 grant no 828774), and by the Spanish Ministry of Science and Innovation (AEI/FEDER grant CTQ2017-84371-P). NMR experiments were performed in the "Manuel Rico" NMR laboratory, LMR, CSIC, a node of the Spanish Large-Scale National Facility ICTS R-LRB. Additional funding from Fundação para a Ciência e Tecnologia (FCT-MCTES) is also acknowledged for DA Mendonça (PD/BD/136752/2018) and for C. Cruz-Oliveira and I. Cadima-Couto (PTDC/BIA-VIR/29495/2017).

IntroductionHIV‐1‐associated CD4+ T‐cell depletion is a consequence of uninfected cell death. Nef is one of the viral factors that trigger apoptosis on bystander cells, though the plasma Nef levels do not correlate with Th lymphocytes counts. The aim of our study was to evaluate whether anti‐Nef antibodies were involved in paediatric AIDS development and whether they can prevent the CD4+ T‐cell depletion in vertically infected children.MethodsTwo hundred and seventy three HIV‐1 vertically infected children seen at Garrahan Paediatric Hospital were randomly included in the study, adding 13 selected cases: seven LTNP (long‐term non‐progressors) and six RP (rapid progressors) children (ntotal=286). Specific anti‐HIV‐1‐Nef antibodies were titrated by indirect ELISA and compared between groups. The plasma blocking effect on Nef‐dependent cytotoxicity was evaluated in Jurkat cells using recombinant Nef as apoptotic stimulus and patient plasmas as blockers, measuring the apoptotic levels using Annexin‐V stain and flow cytometry.ResultsOnly 63.4% of the patients had specific anti‐Nef antibodies, and the levels of anti‐Nef antibodies found in the selected LTNPs plasmas were always significantly higher (p=1.55×10−4) than those in RPs or general HIV‐1+ paediatric populations. The LTNPs' plasma had a strong inhibitory effect on Nef‐dependent cytotoxicity even at high dilutions, while RP plasmas had little or no effect on Nef‐induced apoptosis.Discussion and conclusionsHigh anti‐Nef antibody levels are associated and predict slow or non‐progression to AIDS in vertically HIV‐1‐infected children. They could be an efficient tool in preventing Nef‐associated bystander effect, preserving CD4+ T‐cells and the immune function in the context of paediatric HIV‐1 infection.

Reconhecendo a relevância do incremento na oferta de testagem anti-HIV, problematiza-se a concepção de oferta à luz dos conceitos de acesso e demanda. O mero foco na oferta da testagem mostra-se insuficiente frente à complexidade e dinamicidade do processo, desde a identificação da sua necessidade até a realização do teste e seus possíveis desdobramentos, incluindo o tratamento. Ademais, o modelo de campanha para incentivo à testagem não se coaduna com proposições que valorizem o protagonismo social dos cidadãos nem atendam às especificidades da disseminação da epidemia de AIDS. Postula-se a importância de desenvolver estudos que focalizem mais detidamente a demanda por testagem anti-HIV.

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Economics from the NOVA – School of Business and Economics ; In many Sub-Saharan African countries, governments and international aid agencies have made progress towards a universal antiretroviral treatment coverage. However, a great proportion of HIV infected individuals is not aware of its HIV status and do not take advantage of the benefits from knowing their status. This project aims to analyze the impact of a country antiretroviral treatment coverage on the individuals` decision to get tested for HIV, and thus on their demand for knowing their HIV status. I find a positive relation between individual decision to get tested and antiretroviral treatment, suggesting that individuals are more likely to perform the HIV test where antiretroviral treatment is widely available.