DREAM Program

Maputo, Mozambique

DREAM Program

Maputo, Mozambique
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Ciccacci C.,University of Rome Tor Vergata | Ciccacci C.,Irccs Centro Neurolesi Bonino Pulejo Messina | Borgiani P.,University of Rome Tor Vergata | Ceffa S.,DREAM Program | And 8 more authors.
Pharmacogenomics | Year: 2010

Aims: Nevirapine is widely used to treat HIV-1 infection to prevent mother-to-child transmission; unfortunately adverse drug reactions have been reported. Our aim was to identify genes/variants involved in nevirapine-induced hepatotoxicity. Materials & methods: Patients from Mozambique, 78 with nevirapine-induced hepatotoxicity and 78 without adverse events, were genotyped for ABCB1, CYP2B6, CYP3A4 and CYP3A5 gene variants. We conducted a case-control association study and a genotype/phenotype correlation analysis. Results: The ABCB1 c.3435C>T SNP was associated with hepatotoxicity (p = 0.038), with the variant T allele showing a protective effect (odds ratio: 0.42). Moreover, four SNPs in the CYP2B6 and CYP3A5 genes resulted significantly correlated with transaminase values. In particular, for the CYP2B6 c.983T>C SNP, the difference in the alanine aminotransferase mean values were highly significant between TT and TC genotypes (p < 0.001). Conclusion: Our preliminary results confirm the contribution of the ABCB1 c.3435C>T SNP in nevirapine-induced hepatotoxicity risk and, at the same time, suggest the necessity for further studies. © 2010 Future Medicine Ltd.


PubMed | DREAM Program, University of Rome Tor Vergata, University LUMSA, University of California at Los Angeles and Instituto Superiore Of Sanita
Type: Journal Article | Journal: Epidemiologia e prevenzione | Year: 2015

HIV and malnutrition are the two major causes of infant mortality in Sub-Saharan Africa. The study describes the impact of malnutrition on motor milestone development in HIV-exposed children.Randomized community intervention trial (SMAC, Safe Milk for African Children).Growth, motor development, and malnutrition were assessed in a sample of 76 HIV-exposed children, aged 0-24 months, at the Blantyre Dream Centre in Malawi.We assessed growth and selected motor milestone achievement in agreement with WHO/UNICEF criteria. Odds ratios and 95%confidence intervals were calculated according to motor milestones and malnutrition indices. Multivariable logistic regression was performed with 18 months data.High rates of malnutrition were observed. Underweight increased by 6.7/9.2 and 3.2/5.5 the odds of not standing alone and not walking alone at 15 and 18 months. Stunting increased by 9.7 the odds of not standing alone at 11 months and by 6.1 the odds of not walking alone at 18 months. Wasting increased by 5.5/10.3 the odds for not walking with assistance at 12 and 18 months. Low weight for age was associated with delay in walking at 18 months (HR=2.9).Malnutrition in HIV-exposed children decreases the likelihood of adequate development.


PubMed | Malawi Ministry of Health, University of California at Los Angeles, DREAM Program, University of Rome Tor Vergata and 3 more.
Type: Journal Article | Journal: Journal of the International Association of Providers of AIDS Care | Year: 2016

Combination antiretroviral therapy has been shown to reduce HIV transmission and incident infections. In recent years, Malawi has significantly increased the number of individuals on combination antiretroviral drugs through more inclusive treatment policies. Using a retrospective observational cohort design, records with HIV test results were reviewed for pregnant women attending a referral hospital in Malawi over a 5-year period, with viral load measurements recorded. HIV prevalence over time was determined, and results correlated with population viral load. A total of 11 052 women were included in this analysis, with 440 (4.1%) HIV infections identified. HIV prevalence rates in pregnant women in Malawi halved from 6.4% to 3.0% over 5 years. Mean viral loads of adult patients decreased from 120 000 copies/mL to less than 20 000 copies/mL. Results suggest that community viral load has an effect on HIV incidence rates in the population, which in turn correlates with reduced HIV prevalence rates in pregnant women.


PubMed | DREAM Program, Health Center, University of Rome Tor Vergata, LUMSA University and Instituto Superiore Of Sanita
Type: | Journal: Journal of virological methods | Year: 2016

Assessing treatment efficacy and early infant diagnosis (EID) are critical issues in HIV disease management. Point-of-care assays may greatly increase the possibility to access laboratory monitoring also in rural areas. Recently two new laboratory tests have been developed by Cepheid (Sunnyvale, California) the Xpert HIV-1 Viral Load for viral load determination and the Xpert HIV-1 Qualitative for early infant diagnosis. We conducted a study in Blantyre, Malawi, comparing the 2 methods versus the Abbott real time quantitative and qualitative assays, for viral load and EID respectively. We tested 300 plasma samples for viral load determination and 200 samples for infant diagnosis. HIV-1 RNA values of the 274 samples quantified by both assays were highly correlated (Pearson r=0.95, R(2)=0.90). In 90.9% of the cases the two methods were concordant in defining the HIV-1 RNA levels as detectable or undetectable. For EID, the Xpert HIV-1 Qualitative assay yielded the same identical results as the Abbott assay. Both the quantitative and the qualitative Xpert assays are promising tools to monitor treatment efficacy in HIV patients receiving treatment and for early diagnosis in HIV-exposed infants.


Nucita A.,Messina University | Bernava G.M.,CNR Institute of Clinical Physiology | Giglio P.,DREAM Program | Peroni M.,DREAM Program | And 4 more authors.
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2013

The emerging and growing use of electronic medical records (EMRs) nowadays gives the possibility of exploiting the huge amount of collected clinical data for epidemiological research purpose, together with the opportunity to address and verify intervention policies and facility management. In this paper we present a Markov chain based model that makes use of real clinical data to simulate epidemiological scenarios for HIV epidemic at a district level. Ad hoc original software has been used, that can be adopted in every similar scenario. This research project is conducted within the Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) Program to fight HIV/AIDS in sub-Saharan Africa. The results of this paper show in a clear and robust fashion how the proposed Markov chain based model can be helpful to predict epidemiological trends and hence to support decision making to face the diffusion of HIV/AIDS and other sexually transmitted diseases. © Springer-Verlag 2013.


Ciccacci C.,University of Rome Tor Vergata | Di Fusco D.,University of Rome Tor Vergata | Marazzi M.C.,LUMSA University | Zimba I.,DREAM Program | And 5 more authors.
European Journal of Clinical Pharmacology | Year: 2013

Purpose: Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor, widely prescribed for type 1 human immunodeficiency virus infection. A small proportion of individuals treated with NVP experience severe cutaneous adverse events, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Our aim was to verify whether genetic variability in NVP-metabolizing cytochromes or in transporter genes could be involved in susceptibility to SJS/TEN. Methods: Twenty-seven patients with NVP-induced SJS/TEN and 78 controls, all from Mozambique, were genotyped for the ABCB1 and ABCC10 transporter genes and for CYP2B6, CYP3A4 and CYP3A5 cytochrome gene variants. A case-control and a genotype-phenotype analysis were performed. Results: CYP2B6 G516T and T983C single nucleotide polymorphisms (SNPs) were found to be associated with SJS/TEN susceptibility. The 983C allele in particular was found to be highly associated with a higher risk to develop SJS/TEN [odds ratio (OR) 4.2, P = 0.0047]. The GT haplotype (wildtype for both SNPs) showed a protective effect, with an OR = 0.33 (P = 0.0016). Conclusions: This is the first study showing that genetic variability in a metabolizing enzyme can also contribute to NVP-induced SJS/TEN susceptibility. © 2013 Springer-Verlag Berlin Heidelberg.


Palombi L.,University of Rome Tor Vergata | Pirillo M.F.,Instituto Superiore Of Sanita | Andreotti M.,Instituto Superiore Of Sanita | Liotta G.,University of Rome Tor Vergata | And 11 more authors.
Antiviral Therapy | Year: 2012

Background: Limited information is available on antiretroviral concentrations in women/infant pairs receiving prophylaxis for breastfeeding transmission of HIV and on the relationship between drug levels and the virological and haematochemistry parameters. Methods: Patient population included HIV-positive pregnant women receiving antiretroviral prophylaxis from gestational week 25 until 6 months after delivery and their breastfed infants. Blood and breast milk samples were collected at delivery, and at months 1, 3 and 6 postpartum. Drug concentrations were measured by liquid chromatography-mass spectrometry. Results: Overall, 66 women were studied: 29 received zidovudine (ZDV), lamivudine (3TC) and nevirapine (NVP), 28 stavudine (d4T), 3TC and NVP, and 9 ZDV, 3TC and lopinavir/ritonavir (LPV/r). Women who received >9 weeks of pre-partum prophylaxis were significantly more likely to have an undetectable viral load both in plasma and in breast milk at delivery. No emergence of resistance mutations was observed in breast milk. Breast milk/plasma concentration ratios were 0.6 for ZDV, 3TC and NVP, 1.0 for d4T and 0.4 for LPV/r. Only NVP reached significant levels in the infants. No correlation with any adverse events, including infant anaemia, was observed with drug concentrations. Two infants who acquired HIV infection had non-nucleoside reverse transcriptase inhibitor mutations at month 6. Conclusions: Maternal administration of these three regimens up to 6 months postpartum was effective and safe for both mothers and infants. No significant correlation was found between drug concentrations and infant haematological parameters, supporting the hypothesis that other factors may contribute to the development of anaemia in these settings. ©2012 International Medical Press.


Andreotti M.,Instituto Superiore Of Sanita | Pirillo M.,Instituto Superiore Of Sanita | Guidotti G.,DREAM Program | Ceffa S.,DREAM Program | And 11 more authors.
Journal of Clinical Virology | Year: 2010

Background: The use of simplified methods for viral load determination could greatly increase access to treatment monitoring of HIV patients in resource-limited countries. Objective: The aim of the present study was to optimize and evaluate the performance of the Roche COBAS Taqman assay in HIV-RNA quantification from dried blood spots (DBS) and dried plasma spots (DPS). Study design: EDTA blood samples from 108 HIV-infected women were used to prepare 129 DBS and 76 DPS on Whatman 903 card. DBS and DPS were stored at -20 °C. HIV-1 RNA was extracted from DBS/DPS using the MiniMAG system (bioMerieux). Amplification and detection were performed using the Roche COBAS TaqMan assay. Plasma viral load results were used as standard. Results: There was a high correlation between measures of viral load in plasma and in DBS/DPS (r = 0.96 and 0.85 respectively, P < 0.001). Overall, viral load values in DBS and DPS tended to be lower than in plasma with mean (SD) differences of 0.32 log (0.22) for DBS and of 0.35 (0.33) for DPS. Detection rates were 96.4% for DBS and 96.1% for DPS in samples with corresponding plasma values >3.0 log copies/ml. Samples with HIV-RNA below 50 copies/ml were correctly identified in 18/19 DBS and in 7/7 DPS. Conclusions: Both DBS and DPS provided results highly correlated to the plasma values. High detection rate was obtained with both DBS and DPS when HIV-RNA was >3.0 log copies/ml. Our results support the use of DBS/DPS to detect virologic failure in resource-limited settings. © 2009 Elsevier B.V. All rights reserved.


PubMed | DREAM Program, University of Rome Tor Vergata, LUMSA University and Instituto Superiore Of Sanita
Type: Journal Article | Journal: Medical microbiology and immunology | Year: 2016

Antiretroviral therapy has been shown to reduce rates of congenital CMV infection. Little information is available on the possible impact of antiretroviral therapy on postnatal breastfeeding-associated CMV infection acquisition. A cohort of 89 HIV-infected mothers and their children was studied. Women received antiretroviral therapy from week 25 of gestation until 6months postpartum or indefinitely if meeting the criteria for treatment. All women were evaluated for CMV IgG presence and CMV DNA in breast milk. Children were tested for CMV infection by either the presence of IgM or the presence of CMV DNA in plasma at 1, 6 and 12months and by the presence of IgG at 24months. All mothers had high titers of CMV DNA in breast milk (5.7 log at Month 1 and 5.1 log at Month 6). Cumulative CMV infection rates were 60.3% at Month 6, 69% at Month 12 and 96.4% at Month 24. There was a significant negative correlation between the duration of antiretroviral treatment during pregnancy and levels of CMV DNA in breast milk at Month 1 (P=0.033). There was a trend for a correlation between high titers of CMV DNA in breast milk at 6months and CMV infection at 6months (P=0.069). In this cohort, more than 95% of the children had acquired CMV infection by 2years of age. Besides breastfeeding, which played a major role, also horizontal transmission between 1 and 2years was certainly relevant in determining CMV infection acquisition.


PubMed | DREAM Program, University of Rome Tor Vergata, LUMSA University and Instituto Superiore Of Sanita
Type: Journal Article | Journal: The Journal of antimicrobial chemotherapy | Year: 2015

The objective of this study was to determine the prevalence of drug resistance mutations among HIV-positive women in Malawi 18 months after discontinuing nevirapine-based ART for the prevention of mother-to-child transmission.HIV-infected antiretroviral-naive (except for single-dose nevirapine) pregnant Malawian women receiving a nevirapine-based triple antiretroviral regimen from Week 25 of gestation until 6 months of breastfeeding were included in this analysis. Drug resistance was assessed in HIV-DNA 24 months post-partum and at baseline (before the initiation of treatment). In patients with resistance, the presence of mutations was also evaluated in the corresponding plasma samples.Seven out of 42 (16.7%) women studied had archived drug resistance at Month 24 [six cases had NNRTI-associated mutations and two cases the M184I mutation]. In four cases, resistance mutations were already present at baseline (all NNRTI mutations). In three cases, there was an emergence of new resistance (also present in the plasma in one case). Of the 35 women without resistance mutations at Month 24, only one subject had resistance mutations at baseline. Baseline resistance was significantly more common among women with mutations at 24 months compared with those harbouring a WT virus (4/7 versus 1/35, P < 0.001).Among women who had discontinued drugs 6 months post-partum, only 3/42 (7.1%) had accumulated new resistance mutations in HIV-DNA 2 years after delivery. These findings are reassuring in terms of the safety of the Option B strategy for the prevention of HIV mother-to-child transmission.

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