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Few studies have compared clinical outcomes in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) infants in the current scenario of universal and lifelong maternal antiretroviral therapy (ART). HIV-uninfected and HIV-infected Malawian women receiving ART and their breastfed infants were followed for 12 months postpartum, analyzing the rates of infectious and noninfectious events and assessing infant growth at 6 weeks, 6 months, and 12 months. The cohorts included 227 mothers (70 HIV-negative, 157 HIV-positive) and 235 infants (72 HUU, 163 HEU). No maternal or infant deaths occurred during follow-up. HIV-negative women were less likely to complete follow-up (48.6% versus 91.1%). Mothers with and without HIV had similar rates of both infectious and noninfectious events per person-month. Infants who were HEU, compared with HUU, had higher rates of events of any type, lower respiratory tract infections (LRTI), and noninfectious events. HEU had lower body mass index (BMI) at 6 weeks but did not differ from HUU in all anthropometric measures at 6 and 12 months; in growth between 6 weeks and 12 months; and in occurrence of stunting, underweight, and wasting at 6 weeks, 6 months, and 12 months. During the first year of life, infants who were HEU, compared with HUU, showed a transiently lower BMI and an increased risk of LRTI.

Background The evaluation of immunological status with respect to vaccine-preventable infectious diseases allows to identify populations with suboptimal protection. HIV-exposed infants, even if not infected with HIV, have higher morbidity and mortality in comparison to their unexposed counterparts, and even if the underlying mechanisms have not been clearly elucidated, dysfunctional immune responses might be involved. The aim of this study was to evaluate post-vaccination immune responses in two groups of infants (HIV-exposed and HIV-unexposed) living in the area of Blantyre, Malawi, measuring IgG levels against Haemophilus Influenzae type B (HiB), Hepatitis B (HBV), and Streptococcus pneumoniae (PCP). Methods Sixty-two infants, 49 HIV-exposed, uninfected (HEU), born to women living with HIV, and 13 HIV-unexposed, uninfected (HUU), born to HIV-negative mothers, were included in the study. The infants were visited monthly, from birth to 12 months, and blood samples were collected at 6 months. Anti-HiB, -HBV and -PCP vaccines are administered in Malawi at 6, 10, and 14 weeks of life. The antibody responses to the vaccines were determined by ELISA tests. Results The geometric mean concentrations (GMCs) of anti-HiB, anti-HBs and anti-PCP antibodies were not different between the two groups. The proportion of infants with protective levels (> 0.15 mg/l) versus HiB was lower (although not significantly) in HEU in comparison to HUU infants (81.6% vs 100%, p = 0.095). There was no significant difference between the two groups in the proportion of infants with protective antibody levels against HBV or PCP, although this proportion was lower than expected in both groups, varying from 81.6–84%. Overall, only 61.3% of the infants showed protective levels against all three vaccine antigens. Conclusions The humoral response after vaccination was similar in HEU and HUU infants. A disturbingly high proportion of infants without protective antibody levels against HBV and PCP in both groups of infants and against HiB in HEU infants was observed.

The Short Functional Geriatric Evaluation (SFGE) is a multidimensional and short questionnaire to assess biopsychosocial frailty in older adults. This paper aims to clarify the latent factors of SFGE. Data were collected from January 2016 to December 2020 from 8800 community-dwelling older adults participating in the “Long Live the Elderly!” program. Social operators administered the questionnaire through phone calls. Exploratory factor analysis (EFA) was carried out to identify the quality of the structure of the SFGE. Principal component analysis was also performed. According to the SFGE score, 37.7% of our sample comprised robust, 24.0% prefrail, 29.3% frail, and 9.0% very frail individuals. Using the EFA, we identified three main factors: psychophysical frailty, the need for social and economic support, and the lack of social relationships. The Kaiser–Meyer–Olkin measure of sampling adequacy was 0.792, and Bartlett’s test of sphericity had a statistically significant result (p-value < 0.001). The three constructs that emerged explain the multidimensionality of biopsychosocial frailty. The SFGE score, 40% of which is social questions, underlines the crucial relevance of the social domain in determining the risk of adverse health outcomes in community-dwelling older adults.

The worldwide aging and the increase of chronic disease impacted the Health System by generating an increased risk of admission to Long-Term Care (LTC) facilities for older adults. The study aimed to evaluate the admission rate to LTC facilities for community-dwelling older adults and investigate factors associated with these admissions. A secondary data analysis stemming from an observational longitudinal cohort study (from 2014 to 2017) was performed. The sample was made up by 1246 older adults (664 females and 582 males, mean age 76.3, SD ± 7.1). The LTC facilities access rate was 12.5 per 1000 observations/ year. Multivariable Linear Regression identified frailty, cardiovascular disease, and incapacity to take medicine and manage money as predictors of the LTC facilities’ access rate. The Multiple Correspondence Analysis identified three clusters: those living at home with comorbidities; those living in LTC facilities who are pre-frail or frail; those very frail but not linked to residential LTC. The results indicate that access to LTC facilities is not determined by severe disability, severe comorbidity, and higher frailty levels. Instead, it is related to moderate disability associated with a lack of social support. Therefore, the care policies need to enhance social interventions to integrate medical, nursing, and rehabilitative care.

Background The COVID-19 epidemic in Italy has severely affected people aged more than 80, especially socially isolated. Aim of this paper is to assess whether a social and health program reduced mortality associated to the epidemic. Methods An observational retrospective cohort analysis of deaths recorded among >80 years in three Italian cities has been carried out to compare death rate of the general population and “Long Live the Elderly!” (LLE) program. Parametric and non-parametric tests have been performed to assess differences of means between the two populations. A multivariable analysis to assess the impact of covariates on weekly mortality has been carried out by setting up a linear mixed model. Results The total number of services delivered to the LLE population (including phone calls and home visits) was 34,528, 1 every 20 day per person on average, one every 15 days during March and April. From January to April 2019, the same population received one service every 41 days on average, without differences between January-February and March-April. The January-April 2020 cumulative crude death rate was 34.8‰ (9,718 deaths out of 279,249 individuals; CI95%: 34.1–35.5) and 28.9‰ (166 deaths out of 5,727 individuals; CI95%:24.7–33.7) for the general population and the LLE sample respectively. The general population weekly death rate increased after the 11th calendar week that was not the case among the LLE program participants (p Conclusions LLE program is likely to limit mortality associated with COVID-19. Further studies are needed to establish whether it is due to the impact of social care that allows a better clients’ adherence to the recommendations of physical distancing or to an improved surveillance of older adults that prevents negative outcomes associated with COVID-19.

Introduction:some studies reported that 25.5% of African population presents hypercholesterolemia; however, epidemiology of hypercholesterolemia in Africa is poorly described. Mozambique is experiencing a constant growth of non-communicable diseases, but scarce data are available about hypercholesterolemia. Our study aims at describing the prevalence of hypercholesterolemia in patients with diabetes and hypertension in Mozambique and investigate possible risk factors. Methods:we conducted a cross-sectional study involving all the patients diagnosed with hypertension and/or diabetes from June 2018 to November 2020 in the Zimpeto DREAM Centre (Maputo, Mozambique). For each patient, anthropometric, clinical and laboratory data were collected. Hypercholesterolemia was defined as total blood cholesterol >200 mg/dL. Univariable and multivariable analysis were perfumed. Results:a total of 885 patients were included, 76.2% (n=674) female. Hypertension alone was diagnosed in 670 (75.7%) patients, diabetes in 109 (12.3%) patients and 106 (11.9%) both diseases. Hypercholesterolemia was present in 410 (46.3%) patients and it was more prevalent in patients diagnosed with both diabetes and hypertension (52.8%), as compared to the patients diagnosed with hypertension (46.9%) or diabetes alone (36.7%). In the multivariable analysis, the only factors independently associated with hypercholesterolemia were female sex (aOR 1.77, 95% CI 1.26-2.48, p=0.001) and a body mass index >25kg/m2(aOR 1.50, 95% CI 1.11-2.04, p=0.008). Conclusion:our results highlight the need for a specific focus on female and obese/overweight patients, especially if diagnosed with both hypertension and diabetes, to promptly detect metabolic disorders and establish temporary preventive measures for cardiovascular events.

The aim of this paper is to describe the protocol of a study assessing the impact of a Community-based pro-Active Monitoring Program, by measuring the effect in counteracting the adverse outcomes related to frailty. Methods a prospective pragmatic trial will be carried out to describe the impact of an intervention on people aged>80, adjusted for relevant parameters: demographic variables, comorbidities, disability and bio-psycho-social frailty. They have been assessed with the Functional Geriatric Evaluation questionnaire that is a validated tool. Mortality, Acute Hospital Admission rates, Emergency Room Visit rates and Institutionalization rates are the main outcomes to be evaluated annually, over three years. Two groups of patients, made up by 578 cases (undergoing the intervention under study) and 607 controls have been enrolled and interviewed. Results at baseline the two groups are quite similar for age, living arrangement, comorbidity, disability and cognitive status. They differ in education, economic resources and physical status (that are better in the control group) and in social resources (that is better in the case group). The latter was expected since the intervention is focused on increasing social capital at individual and community level and aimed at improving survival among the cases as well as reducing the recourse to hospital and residential Long Term Care. Conclusion The proposed study addresses a crucial issue: assessing the impact of a bottom up care service consisting of social and health interventions aimed at reducing social isolation and improving access to health care services.

Background: Lowering mortality and hospitalization of older adults is one of the main goals of public health to improve both health systems' sustainability and older adults' quality of life. The aim of this study is to identify the determinants associated with mortality and the use of hospital services in the population older than 64 years of age. Methods: A randomized sample from the population of the Lazio region (Italy) above the age of 64 was enrolled in 2014 by the administration of a questionnaire to assess frailty; the rates of use of hospital services and mortality in the year following the enrolment have been retrieved by the regional database. Univariable and multivariable analyses addressed the association of health status, social and economic variables with health outcomes. Results: One thousand two hundred and eighty persons were recruited; 52 deaths were reported at 1 year of follow-up (robust 1.8%, frail 10.1% and very frail 19.1%, P < 0.001). The mean rate of use of hospital services was 692.2 per 1000 observation/year (robust 589.5, frail 1191.1 and very frail 848.4, P < 0.001). In the multivariate analysis, the higher rate of use of hospital services was independently associated with functional status, social support, psychological/psychiatric discomfort, availability of home care services and physical health. Conclusions: Frailty, as a multidimensional issue, is also a strong predictor of survival in the short term. The use of the hospital services by older adults is associated mainly with functional status, social resources, psycho-physical status and health service organization factors.

Introduction. Frailty represents a major risk factor for death and Use of Hospital Services (UHS) among older adults. A simple tool to detect frailty might permit stratification of the community-dwelling older population according to the risk of negative outcomes. The present study aims at determining the sensitivity and specificity in predicting mortality and UHS of the Short Functional Geriatric Evaluation (SFGE), a short questionnaire to screen for frailty in community-dwelling older citizens. Methods. The study is a secondary analysis of all the data collected through an observational longitudinal cohort study carried out in Lazio region (Italy). The SFGE is compared with the Functional Geriatric Evaluation (FGE) questionnaire to define sensitivity and specificity for mortality and for UHS during the first year following its administration. Results. The SFGE classifies 36.3% of the respondents as frail and shows a sensitivity of 90.4% and a specificity of 78.3% compared to the FGE (area under the ROC: 0.928; CL95%: 0.910 - 0.947; p-value < 0.001). Those respondents identified by the SFGE as frail also include some of those classified by the FGE as pre-frail, who also show a high rate of UHS. The results show that the SFGE score predicts the UHS more accurately than it does the mortality rate. Conclusion. The SFGE identifies as frail a larger portion of the enrolled population than the FGE. Those people so identified show a high rate of UHS. Because of its easy and quick administration, it can be considered a useful primary screening tool but it must be followed up with a more extensive assessment of those identified as frail. The small time needed to fill in the tool and the possibility of administering it by telephone makes the SFGE a useful tool to screen for frailty and to plan the provision of care services at both individual and population level.

In this study, we analysed in a cohort of pregnant women followed for two years the proportion of women remaining at the same clinic, those who transferred to other clinics, and those lost to follow-up. The possible determinants of the loss to follow-up were also assessed in a setting of postpartum discontinuation based on CD4+ count. A total of 311 pregnant women received antiretroviral therapy from week 25 of gestational age until six months postpartum (end of breastfeeding period), or indefinitely if meeting the criteria for treatment (baseline CD4+ 3). Twenty-four months after delivery, six women had died, 247 were in active follow-up, 21 had transferred to another antiretroviral therapy clinic and 37 were lost to follow-up (rate of loss to follow-up 13%, 95% CI 9.1–16.9%). The presence of a baseline CD4+ count above 350 cells/mm3 was associated with a ten-fold higher risk of loss to follow-up after six months of delivery (hazard ratio: 9.8, 95% CI 2.2–42.7, for baseline CD4 >350 cells/mm3 versus baseline CD4+ count below 350 cells/mm3, p = 0.002). This finding suggests that discontinuation of drugs when the risk of transmission has ceased can have a negative impact on the retention in care of these women.

This study focuses on the impact of a program aimed at reducing heat-related mortality among older adults residing in central Rome by counteracting social isolation. The mortality of citizens over the age of 75 living in three Urban Areas (UAs) located in central Rome is compared with that of the residents of four adjacent UAs during the summer of 2015. The data, broken down by UA, were provided by the Statistical Office of the Municipality of Rome, which gathers them on a routine basis. During the summer of 2015, 167 deaths were recorded in those UAs in which the Long Live the Elderly (LLE) program was active and 169 in those in which it was not, implying cumulative mortality rates of 25‰ (SD ± 1.4; Cl 95%: 23–29) and 29‰ (SD ± 6.7; Cl 95%: 17–43), respectively. Relative to the summer of 2014, the increase of deaths during the summer of 2015 was greater in UAs in which the LLE program had not been implemented (+97.3% vs. +48.8%). In conclusion, the paper shows the impact of a community-based active monitoring program, focused on strengthening individual relationship networks and the social capital of the community, on mortality in those over 75 during heat waves.

Introduction: Social isolation increases in the over-74 population and it is a risk factor for death and Long Term Care (LTC) use. In order to prevent the negative consequences of social isolation on this population community interventions focused on strengthening the social network should be intensified. The aim of this paper is to describe the impact on health care use of a Community-based pro-Active Monitoring Program (CAMP) providing phone monitoring to all the clients and home visits according to the individual’s needs. Methodology: In order to provide an evaluation of the program outcomes, the rates of clients’ hospitalization and admissions to Long Term Care facilities during 2011 have been assessed. The observed rates have been compared with expected ones calculated on available information for similar population. A cost-analysis has been also carried out to analyze the program sustainability. Results: The studied sample is made up by 1408 over-74 citizens followed up during 2011 in Rome (Italy) by CAMP. The cumulative observation time was 1362 p/y; 61 individuals died during 2011 (death rate 4.3%). The hospital admission rate observed among CAMP’s clients was 254‰ (357/1408; CL95% ± 91‰), lower than the 282‰ reported for the over-74 population of Rome. This translates into 39 averted hospitalization. The LTC admission rate is also reduced among CAMP’s clients (9/1,408, 6.6‰ CL95% ± 0.8‰ vs. 9.7‰ reported for a comparable sample); it translates into 4 averted LTC admissions. The averted cost ranged between 47,153 �and 220,117 �according to the range of services used by the clients, which translates into a percentage of estimated cost reduction on yearly basis ranged between 3% and 12.5% of the whole cost of services used by the studied population. Discussion: The paper suggests the capacity of CAMP to reduce both the over-74 hospitalization rate and use of LTC. Cost analysis also indicates a cost reduction as a consequence of the CAMP implementation. Further studies including a control group and a detailed cost-benefit analysis are needed to check the program sustainability on larger population.

We used high-resolution phylogenetic methods in the context of mother-to-child transmission to obtain information on the timing of the infection and on the transmission network. A total of 33 pol sequences (from maternal peripheral blood, from breast milk, and from plasma of children) belonging to five cases of HIV infant transmission were studied. Using time-scaled phylogeny we were able to estimate that in two cases the transmission occurred after the recommended duration of breastfeeding, supporting a longer, not reported, duration of breastfeeding as a significant factor associated with HIV infant acquisition in this cohort. Among the postnatal infections we were also able to demonstrate that the cell-free virus in breast milk was the most likely population associated with the event of transmission. Our study showed that a coalescent-based model within a Bayesian statistical framework can provide important information that can contribute to optimizing preventive strategies.

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 6 months 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 12 months and by the presence of IgG at 24 months. 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 6 months and CMV infection at 6 months (P = 0.069). In this cohort, more than 95 % of the children had acquired CMV infection by 2 years of age. Besides breastfeeding, which played a major role, also horizontal transmission between 1 and 2 years was certainly relevant in determining CMV infection acquisition.

The objective of this study was to determine the virological response and the possible emergence of drug resistance at 1 and 2 years postpartum in HIV-positive pregnant women enrolled under the Option B approach and meeting the criteria for treatment. In the study, women with baseline CD4(+)350/mm(3) received a combination of stavudine, lamivudine, and nevirapine during pregnancy (from week 25 of gestation) and continued it indefinitely after delivery. HIV-RNA was measured at 12 and 24 months postpartum. Drug resistance mutations were assessed in those with HIV-RNA50 copies/ml. Baseline resistance mutations were assessed in the entire cohort. A total of 107 women were studied. At baseline, resistance mutations were seen in 6.6% of the women. At 12 months, 26.7% of the women had50 copies/ml and among them 12.9% had virological failure (HIV-RNA1,000 copies/ml). At 24 months, detectable HIV-RNA was seen in 28.3% of the women and virological failure in 10.1% of the women. Resistance mutations (mainly non-nucleoside reverse transcriptase inhibitors mutations) were seen in 40% of the women with detectable HIV-RNA. Baseline mutations did not correlate with virological failure or the emergence of resistance at later time points. Virological failure 2 years postpartum and emergence of resistance were rare in this cohort of HIV-infected women. These findings are reassuring in the light of the new strategies for the prevention of mother-to-child HIV transmission, recommending life-long antiretroviral therapy administration.

The prevalence of frailty is expected to increase worldwide in parallel with demographic ageing. Despite this, little is known about the prevalence in different populations particularly community-based samples. This cross-sectional study evaluates the prevalence of frailty in a community-dwelling older adult population and describes a methodology to plan community-based interventions.A random sample of 1331 older adults, resident in the Lazio-Region of Italy, were screened by trained public health nurses (PHNs) by administering a validated questionnaire (the Functional Geriatric Evaluation questionnaire). Prevalence of frailty was calculated using the Final Synthetic Score derived from the questionnaire's Final Score. Variables associated with frailty were selected through univariate and multivariate statistical analysis.Prevalence of frail (FS≥10,≤50) and very frail (FS10) individuals was 13.9% and 7.6% respectively. Variables associated with frailty were age (older than 85 years), disability, living alone or the presence of a paid carer, lower education and neurological disorders like stroke, dementia, Parkinson disease and other neuropsychiatric diseases; Anaemia or cancer were also associated with a higher prevalence of frailty.The study provide a comprehensive picture of the prevalence of frailty and factors associated to this condition in community-dwelling older adults. On the basis of the study results, a plan of community-based services could address the needs of care of the elderly population. A trained team of PHNs may be the most appropriate personnel to carry out multidimensional frailty assessment in this setting.

INTRODUCTION: scaling up of antiretroviral therapy (ART) to HIV+ pregnant women is crucial for the elimination of HIV infection in children. The aim of this study was to evaluate the feasibility and effectiveness of triple ART for Prevention of Mother-to Child Transmission (PMTCT) in Cameroon. Methods: HIV-positive pregnant women attending the DREAM Centre of Dschang, Cameroon for prenatal care were enrolled in a prospective cohort study, and received ART until the end of breastfeeding or indefinitely if their CD4 count was

Background. The use of antiretrovirals to reduce the incidence of human immunodeficiency virus (HIV) infection has been evaluated in mathematical models as potential strategies for curtailing the epidemic. Cohort data from the Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) Program was used to generate a realistic model for the HIV epidemic in sub-Saharan Africa. Methods. Two combined stochastic models were developed: patient and epidemic models. Models were combined using virus load as a parameter of infectivity. DREAM data that assessed patient care in Mozambique and Malawi were used to generate measures of infectivity, survival, and adherence. The Markov chain prediction model was used for the analysis of disease progression in treated and untreated patients. A partnership model was used to assess the probability that an infected individual would transmit HIV. Results. Data from 26 565 patients followed up from January 2002 through July 2009 were analyzed with the model; 63% of patients were female, the median age was 35 years, and the median observation time was 25 months. In the model, a 5-fold reduction in infectivity (from 1.6% to 0.3%) occurred within 3 years when triple ART was used. The annual incidence of HIV infection declined from 7% to 2% in 2 years, and the prevalence was halved, from 12% to 6%, in 11 years. Mortality in HIV-infected individuals declined by 50% in 5 years. A cost analysis demonstrated economic efficiency after 4 years. Conclusions. Our model, based on patient data, supports the hypothesis that treatment of all infected individuals translates into a drastic reduction in incident HIV infections. A targeted implementation strategy with massive population coverage is feasible in sub-Saharan Africa.

Infant malnutrition in sub-Saharan Africa is a public health priority and a challenge in high HIV prevalence areas. The Drug Resources Enhancement Against AIDS and Malnutrition program, with multiple medical centers in Sub-Saharan Africa, developed an innovative intervention for the surveillance and control of malnutrition. In a pilot initiative, 36 HIV-exposed children were evaluated at baseline upon presentation for malnutrition and at six months post- treatment. Parameters included HIV-free survival, nutritional status and change in diet. Food diary data was entered and processed using the Nutrisurvey (WHO) software. At 6 months post-intervention, a significant improvement in anthropometric parameters was noted. Slowing of linear growth was observed in patients with malaria with a mean gain in centimetres of 4.4 ± 1.7 as compared to 5.6 ± 1.7 in children with no malaria, p < 0.048 (CL 95%: −2.32, −0.01). Dietary diversity scores increased from 5.3 ± 1.9 to 6.5 ± 1.3, p < 0.01 at 6 months. A significant increase (+25%, p < 0.02) in the number of children eating fish meals was noted. Our pilot data describes positive outcomes from a rehabilitative nutritional approach based on use of local foods, peer education, anthropometric and clinical monitoring in areas of high food insecurity. The relationship between malaria and linear growth retardation requires further investigation.

Since February 2002, the Drug Resources Enhancement against AIDS and Malnutrition Program has provided highly active antiretroviral therapy (HAART) and immunologic and virologic monitoring free of charge. We conducted a cohort study of persons infected with human immunodeficiency virus in Mozambique. Only persons treated with HAART with available CD4 cell counts at baseline and ≥ 1 CD4 cell count after HAART were included. Survival analysis was applied to evaluate the prognostic value of CD4 cell counts measured at three months. Possible confounders were considered. A total of 753 persons who started HAART included; 59% were females. Median age was 34 years (range = 16–67 years), and the median CD4 cell count at baseline was 172 cells/mm3 (interquartile range = 87–261 cells/mm3, range = 0–1,322 cells/mm3). Overall, 105 persons (14%) died. Of these persons 54 (51%) developed AIDS before they died; 25 (3%) died during the first three months. After three months of therapy, the individual median CD4 cell count change from the baseline value was +101 cells/mm3 (interquartile range = +27 to +187 cells/mm3, range = –723 to +310 cells/mm3). A median CD4 increment of 100 cells/mm3 in three months was associated with a mortality reduction of 50% compared with an increase of < 50 cells (relative hazard of death adjusted for baseline CD4 cell count = 0.54, 95% confidence interval = 0.30–0.95). A good initial response to HAART was associated with a significant reduction of mortality. This finding supports the effectiveness of HAART in resource-poor settings.

Background: Reduction of HIV-1 breast-feeding transmission remains a challenge for prevention of pediatric infections in Sub-Saharan Africa. Provision of formula decreases transmission but often increases child mortality in this setting. Methods: A prospective observational cohort study of HIV-1 exposed infants of mothers receiving pre and postnatal medical care at Drug Resource Enhancement Against AIDS and Malnutrition centers in Mozambique was conducted. Live-born infants of HIV-1-infected women receiving medical care were enrolled, HIV-1 testing was performed at 1, 6, and 12 months of age using branched DNA. Mothers were counseled to breast-feed exclusively for 6 months and were provided HAART antenatally mid postnatally for the first 6 months. Women with CD4 cell counts less than 350/cmm at baseline continued HAART indefinitely. Results: Of 341 infants followed from birth, 313 mother-infant pairs (92%) completed 6 months and 283 (83%) completed 12 months of follow-up. HIV-1 diagnosis was ascertained in 287 infants (84%) including 4 who died. There were 9 cases of HIV-1 transmission: 4 of 341 (1.2%) at 1 month, 2 of 313 (0.6%) at 6 months, and 2 of 276 (0.7%) at 12 months (cumulative rate: 2.8%). Two mothers (0.6%) and 11 infants (3.2%) died. Maternal and infant mortality rates were 587 of 100,000 and 33 of 1000, while country rates are 1000 of 100,000 and 101 of 1000. HIV risk reduction was 93% and HIV-free survival at 12 months was 94%. Conclusions: Late postnatal transmission of HIV-1 is significantly decreased by maternal use of HAART with high infant survival rates up to 12 months of age.

We evaluated growth indices in two cohorts of Malawian infants exposed to tenofovir, lamivudine and efavirenz in utero and during 12 months of breastfeeding, and to stavudine/zidovudine, lamivudine and nevirapine in utero and during 6 months of breastfeeding. Growth indices were similar in the two cohorts at one and 6 months but were significantly better in the first group at 12 months, suggesting no negative effect of tenofovir and a significant benefit of extended breastfeeding.

Objectives No data are available on bone metabolism in infants exposed to tenofovir during breastfeeding. We investigated bone metabolism markers in the first year of life in infants from mothers who received tenofovir, lamivudine and efavirenz during pregnancy and 12 months of breastfeeding in a national Option B+ programme in Malawi. Methods Serum samples collected at 6 and 12 months in tenofovir-exposed infants and in a small sample of tenofovir-unexposed infants from the same clinical centre were analysed in batches for levels of bone-specific alkaline phosphatase (BAP; marker of bone formation) and of C-terminal telopeptide of type I collagen (CTX; marker of bone resorption). Results Overall, 136 tenofovir-exposed infants were evaluated. No infant had at either timepoint CTX values above the upper normal limit, while most of them had at 6 and 12 months levels of BAP above the upper normal limit for the age range. Levels of bone markers showed no differences by gender and no association with growth parameters. Tenofovir-unexposed and -exposed children had similar mean levels of bone markers at 6 months (CTX: 0.62 versus 0.55 ng/mL, P = 0.122; BAP: 384 versus 362 U/L, P = 0.631). Conclusions No significant association between treatment with tenofovir and CTX or BAP levels was found. The high levels of BAP, coupled to the normal levels observed for CTX, might reflect primarily skeletal growth. Potential negative effects of prolonged exposure to tenofovir through breastfeeding cannot however be excluded and longitudinal studies that evaluate bone mineralization status in children enrolled in Option B+ programmes are warranted.

Objective: Purpose of this study was to assess the prevalence and risk factors associated with development of hepatotoxicity and anemia following initiation of antiretroviral treatment (ART) containing stavudine (d4T) or zidovudine (AZT) in the first year of treatment in the African setting. Method: We evaluated aspartate aminotransferase and haemoglobin levels at baseline and at 1, 2, 3, 6, 9 and 12 months following ART initiation among 10,537 HIV-1 infected, ART-naive, non-pregnant adults in Mozambique and Malawi. The Cox proportional hazards model was used to assess risk factors for hepatotoxicity and anaemia in the first year following ART initiation. Results: The prevalence of ART-associated hepatotoxicity grades 1-2 declined in the first 3 months of ART from 13.5% to 10.8%, and grades 3-4 from 2.0% to 0.2% from month 1 to month 6. The prevalence of hepatotoxicity grades 1-2 peaked at month 6 due to the use of d4T (overall 14.2%; d4T-arm: 16.2%, AZT-arm: 5.8%). Anemia grades 1-2 and 3-4 declined from month 1 (13.3%, 3.2% respectively) to month 12 (3.0%, 0.5%, respectively). Risk factors for hepatotoxicity grades 1-2 included d4T use, an elevated VL pre-ART and female sex, and for anemia grade 1-2 and 3-4 AZT use, female sex and malaria. A high pre-ART VL was associated with the onset of severe anaemia. Not being malnourished was protective against mild hepatotoxicity and anemia. The ART-related mortality observed in the cohort was low (0.017%). Conclusion: In African settings the risk of untreated HIV outweighs the risk of anemia and hepatotoxicity mediated by ART. The prevalence of ART mediated hepatotoxicity declines in the first 3 to 6 months of treatment, and that of anemia declines in the first 12 months of ART. Patients with a poor health status at the start of ART are at highest risk of developing ART-associated hepatotoxicity and anemia.

Frailty is considered a determinant of elderly decline. However the potential negative consequences of frailty on individual health can be prevented by public health prevention program. The aim of this study is to describe the characteristics of frailty in an elderly sample in order to plan an effective community prevention program. A randomized sample of over-64 Lazio region residents, living at home, has been contacted through their General Practitioner. …

The Drug Resource Enhancement against AIDS and Malnutrition Program (DREAM) gathered professionals in the field of Elimination of HIV-Mother-To-Child Transmission (EMTCT) in Maputo in 2013 to discuss obstacles and solutions for the elimination of HIV vertical transmission in sub-Saharan Africa. During this workshop, the benefits of administrating combined antiretroviral therapy (cART) to HIV positive women from pregnancy throughout breastfeeding were reviewed. cART is capable of reducing vertical transmission to less than 5% at 24 months of age, as well as maternal mortality and infant mortality in both HIV infected and exposed populations to levels similar to those of uninfected individuals. The challenge for programs targeting eMTCT in developing countries is retention in care and treatment adherence. Both are intrinsically related to the model of care. The drop-out from eMTCT programs before cART initiation ranges from 33%–88% while retention rates at 18–24 months are less than 50%. Comprehensive strategies including peer-to-peer education, social support and laboratory monitoring can reduce refusals to less than 5% and attain retention rates approaching 90%. Several components of the model of care for reduction of HIV-1 MTCT are feasible and implementable in scale-up strategies. A review of this model of care for HIV eMTCT is provided.

BackgroundAssessment of appropriateness is a criteria of increasing relevance for delivering health care services. In Italy elderly hospital admissions for Chronic Obstructive Pulmonary (COPD) disease is one of the chosen indicators to measure the appropriate use of services. This study describes the characteristics of hospital admissions at a regional level for COPD – DRG 88 and to evaluates their relationship with other indicators linked to the provision of hospital or community care services. MethodsData on hospital admissions for COPD in the years 2006 and 2011 were collected from hospital discharge records. Correlations among acute in-patients admission rates by Italy’s Regions and provision of Long Term Care (LTC) services have been analyzed through univariate and multivariate linear regression models.ResultsThe national rate of hospitalization for COPD decreased from 2006 to 2011 (-35%). The COPD in-patient admission rate showed a weak inverse relation with the provision of LTC that was statistically significant only for 65-74 age-group in 2006. The reduction was greater than 60% for those under the age of 75 and around 14% for those over 74 years.The inclusion in the interpretative model the rate of beds per capita in and the rate of General Practitioners improves the percentage of variability between the regions in the rate of hospitalization for the DRG 88 explained by the model itself.ConclusionThe reduction in hospitalizations for COPD in the over-fifty age group is particularly noticeable; it seems mainly related to factors other than to the operation of those services outside the hospital.

To avoid overdiagnosis, accuracy in the identification of true malaria cases is of critical importance. Samples (either whole blood, dried blood spots or plasma/serum) collected at the time of clinically diagnosed malaria episodes in a cohort of Malawian HIV-infected mothers and their children were retrospectively tested with the enzyme-linked immunosorbent assay (ELISA) for HRP-2 (histidine-rich protein 2) detection. There were 55 and 56 clinically diagnosed cases of malaria in mothers and children, respectively, with samples available for testing. Rates of laboratory-confirmed episodes were 20% (11 of 55) in mothers and 16.1% (9 of 56) in children. Hemoglobin was lower in children with confirmed malaria compared to those with clinical malaria diagnosis. The results of our study support the widespread use of rapid diagnostic tests.

Steven–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe adverse drug reactions, characterized by extensive epidermal detachment and erosions of mucous membrane. SJS/TEN is one of the most serious adverse reactions to Nevirapine (NVP) treatment, commonly used in developing countries as first-line treatment of human immunodeficiency virus infection. In the last years TRAF3IP2 gene variants had been described as associated with susceptibility to several diseases such as psoriasis and psoriatic arthritis. We hypothesized that this gene, involved in immune response and in NF-κB activation, could also be implicated in the SJS/TEN susceptibility. We performed a full resequencing of TRAF3IP2 gene in a population of patients treated with NVP. Twenty-seven patients with NVP-induced SJS/TEN and 78 controls, all from Mozambique, were enrolled. We identified eight exonic and three intronic already described variants. The case/control association analysis highlighted an association between the rs76228616 SNP in exon 2 and the SJS/TEN susceptibility. In particular, the variant allele (C) resulted significantly associated with a higher risk to develop SJS/TEN (p = 0.012 and OR = 3.65 (95% CI 1.33–10.01)). A multivariate analysis by logistic regression confirmed its significant contribution (p = 0.027, OR = 4.39 (95% CI 1.19–16.23)). In conclusion, our study suggests that a variant in TRAF3IP2 gene could be involved in susceptibility to SJS/TEN.

The study included 309 HIV-infected pregnant women receiving a lamivudine-containing antiretroviral regimen from week 25 of gestational age until 6 months postpartum, during breastfeeding. Twenty-seven of them (8.7%) were hepatitis B virus surface antigen (HBsAg) positive; at baseline, hepatitis B virus (HBV) DNA levels >3 log(10) IU/mL (with a median level of 6.2 log(10) IU/mL) were found in 10 women, who at one, three and six months postpartum had median levels of 5.2 log(10) IU/mL, 4.5 log(10) IU/mL and 2.8 log(10) IU/mL, respectively. Twenty-four of the 30 breast milk samples evaluated had undetectable HBV DNA and the other six had values between 15 and 155 IU/mL. Median lamivudine concentrations were 1070 ng/mL in serum and 684 ng/mL in breast milk. Among the 24 HBV-exposed children with available samples, 16 always tested negative, four had a transient infection, one had an undetermined status and three (12.5%) first tested positive at Month 12 or Month 24. Among the children born to the HBV-uninfected mothers of the same cohort, the rate of HBsAg positivity at 12-24 months was 2% (4/196). Our finding of the absence of significative levels of HBV DNA in the breast milk of co-infected mothers supports the present recommendations for breastfeeding in HBV-infected women. Horizontal transmission can be hypothesized for the infections detected in children at 12-24 months. Children born to HBV-positive mothers remained at higher risk of postnatal HBV acquisition compared to those born to HBV-negative women.

HIV-infected children have less access to combination antiretroviral therapy as compared with adults in resource-limited settings. Growth faltering, loss to follow-up (LTFU) and high mortality are frequently seen.A retrospective cohort study was performed with parameters extracted from the Drug Resource Enhancement against AIDS and Malnutrition database for HIV-infected, antiretroviral naïve children under 15 years presenting for care at 17 Drug Resource Enhancement against AIDS and Malnutrition centers in Mozambique, Malawi and Guinea between January 2005 to December 2008. Predictors of time-to-death, time-to-LTFU and persistence of malnutrition by Cox's regression and Kaplan-Meier were determined.2215 children presented to care with 1343 (61%) being ≤ 5 years. At baseline, stunting and malnutrition occurred in 40% and 25%, respectively; 75% of 2149 children had CD4 cell percentages less than 20; median HIV RNA, log10 cp/mL, was 4.97 in 1927 patients. Over time 238 children died (10.7%; 2.7% person-years [PY]) 63 were LTFU (2.8%; 0.7% PY). By multivariate analysis, mortality was associated with virus load (hazards ratio: 1.19; confidence interval: 1.01-1.402, P = 0.038) and reduced weight-for-age Z scores (hazards ratio: 0.590; confidence interval: 0.53-0.66, P0.001). LTFU was associated with low weight-for-height Z scores (hazards ratio: 0.71; confidence interval: 0.51-0.97, P = 0.031). At 12 months after combination antiretroviral therapy, anthropometric parameters significantly improved in 1226 children (P0.001); virus load declined to400 copies/mL in over 60%.Despite advanced HIV disease, children initiating combination antiretroviral therapy had mortality rates of 2.7% p/PY with overall attrition rates of 11.7% p/100 PY, with significant reversal of negative anthropometric markers, and improvement of immunological and virological parameters in children with 12 months of follow-up.

BackgroundOptimized preventive strategies are needed to reach the objective of eliminating pediatric AIDS. This study aimed to define the determinants of residual HIV transmission in the context of maternal antiretroviral therapy (ART) administration to pregnant women, to assess infant safety of this strategy, and to evaluate its impact on maternal disease.Methodology/principal findingsA total of 311 HIV-infected pregnant women were enrolled in Malawi in an observational study and received a nevirapine-based regimen from week 25 of gestation until 6 months after delivery (end of breastfeeding period) if their CD4+ count was > 350/mm(3) at baseline (n = 147), or indefinitely if they met the criteria for treatment (n. 164). Mother/child pairs were followed until 2 years after delivery. The Kaplan-Meier method was used to estimate HIV transmission, maternal disease progression, and survival at 24 months. The rate of HIV infant infection was 3.2% [95% confidence intervals (CI) 1.0-5.4]. Six of the 8 transmissions occurred among mothers with baseline CD4+ count > 350/mm(3). HIV-free survival of children was 85.8% (95% CI 81.4-90.1). Children born to mothers with baseline CD4+ count < 350/mm(3) were at increased risk of death (hazard ratio 2.6, 95% CI 1.1-6.1). Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm(3) was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation.ConclusionsHIV transmission in this cohort was rare however, it occurred in a significative proportion among women with high CD4+ counts. Strategies to improve treatment adherence should be implemented to further reduce HIV transmission. Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage. Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered.

HIV RNA monitoring is not available in most antiretroviral treatment (ART) programs in sub-Saharan Africa; switch to second-line therapy is mostly guided by clinical/immunological criteria. This may lead to unnecessary disease progression and drug resistance accumulation. We investigated the prognostic value of virological and immunological status 6 months after ART initiation with respect to death, loss to follow-up, and treatment switch.We considered treatment-naive HIV-1-infected patients, starting ART with available 6-month visit and subsequent follow-up, enrolled in a prospective cohort comprising 5 ART sites in 3 sub-Saharan countries. Outcome measures included the time from 6-month visit to death for all causes, loss to follow-up, and switch to second line.Of 2539 patients, 62% were females, their median pre-ART CD4 count was 215 cells per microliter, median HIV RNA 4.6 Log10 copies per milliliter, 30% were on WHO stage 3/4. At 6 months, 85% had HIV RNA1000 copies per milliliter. During 3112 person-years follow-up after the 6-month visit, 91 patients died. Death was predicted by 6-month HIV RNA ≥10,000 copies per milliliter, adherence, and 6-month CD4200 cells per microliter. The 2-year estimated probability of surviving ranged from 0.69 (with 6-month HIV RNA ≥10,000 and CD4200) to 0.95 (with HIV RNA1000 and CD4 ≥200). Loss to follow-up (1.95 per 100 person-years follow-up) was predicted by the 6-month HIV RNA10,000 copies per milliliter and adherence but not by CD4. Switch to second line (6.94 per 100 person-years follow-up) was predicted by 6-month HIV RNA and CD4.In patients starting ART in sub-Saharan Africa, 6-month HIV RNA independently predicts subsequent survival, retention to care, and switch to second-line therapy. This measure warrants further evaluation as specific time point monitoring option.