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To evaluate the role of lung ultrasound (LUS) in recognizing lung abnormalities in pregnant women affected by COVID-19 pneumonia.An observational study analyzing LUS patterns in 60 consecutively enrolled pregnant women affected by COVID-19 infection was performed. LUS was performed by using a standardized protocol by Soldati et al. The scoring system of LUS findings ranged from 0 to 3 in increasing alteration severity. The highest score obtained from each landmark was reported and the sum of the 12 zones examined was calculated.Patients were divided into two groups: 26 (43.3%) patients with respiratory symptoms and 32 (53.3%) patients without respiratory symptoms; 2 patients were asymptomatic (3.3%). Among the patients with respiratory symptoms 3 (12.5%) had dyspnea that required a mild Oxygen therapy. A significant correlation was found between respiratory symptoms and LUS score (p0.001) and between gestational weeks and respiratory symptoms (p = 0.023). Regression analysis showed that age and respiratory symptoms were risk factors for highest LUS score (p0.005).LUS can affect the clinical decision course and can help in stratifying patients according to its findings. The lack of ionizing radiation and its repeatability makes it a reliable diagnostic tool in the management of pregnant women.

Objectives: In Italy, the case fatality rate (CFR) of coronavirus disease 2019 (COVID-19) during the first wave of the pandemic showed significant geographic heterogeneity. The aim of this study was to explore the possible association between the CFR and measures of disease burden in the Italian regions using an ecological approach. Methods: Cumulated regional data for the period February 24 to May 11, 2020 were analysed to assess the association of the CFR with the cumulative incidence of COVID-19 and the ratio between the maximum number of COVID-19 patients in intensive care units (ICU) and ICU beds available before the pandemic (ICU load), adjusting for median age of the patients at disease onset, number of nasopharyngeal swabs performed per confirmed case, and prevalence of chronic diseases . Results: During the study period, the COVID-19 CFR in the Italian regions ranged between 5.0% and 18.4%. On multivariable regression analysis, the CFR was found to be significantly associated with the cumulative incidence (relative rate (RR) 1.02 per 100 cases/1 million increase), median patient age (RR 1.07 per 1 year increase), and ICU load (RR 1.72, 2.18, and 2.57, for >40–70% vs ≤40%, 70–140% vs ≤40%, and ≥140 vs ≤40%, respectively). Conclusions: A high burden of COVID-19 may contribute to increased disease fatality, possibly as a result of the increasing demand for care of critically ill patients beyond health system capability.

T helper (Th) cell subsets play distinct and important roles during pregnancy. This work was focused on investigating the Th and cytokine profile in pregnant women recovered from COVID-19. To this aim, the frequency of Th1, Th2, Th17 subsets and the level of associated cytokines were analysed in pregnant women recovered from COVID-19 and in matched non-pregnant women. Principal component analysis highlighted a significant impact of pregnancy on Th profile with an increase of ex-Th17 subset and a parallel decrease of Th1 population. These modulations may participate in both preserving the pregnancy and reducing the risk of severe infection.

Highlights • Acute respiratory distress syndrome due to SARS-CoV-2 and Influenza A co-infection. • Challenging in co-infection cases identification. • Improvement of preventive measures and patients’ clinical outcome., A case of acute respiratory distress syndrome due to SARS-CoV-2 and Influenza A co-infection and a mini-review of the literature is reported. Even in COVID-19 epidemics, the early identification of concurrent respiratory pathogens is important to improve etiological diagnosis, preventive measures and patients’ clinical management and outcome.

Background Few data about predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS) are available. Methods Retrospective study including all patients admitted with COVID-19 in an Italian reference hospital for infectious diseases between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between duration of VS and probability of clinical outcomes was evaluated through inverse probability weighted Cox model. Results 536 subjects were included. Median duration of VS from symptoms onset was 18 days (IQR 12-26). The estimated 30-day probability of VC was 70.2% (95%CI:65-75). At multivariable analysis, patients with comorbidities (aIRR = 0.88, p = 0.004), lymphopenia at hospital admission (aIRR = 0.75, p = 0.032) and with moderate/severe respiratory disease (aIRR = 0.42, p 1000 ng/mL at admission (aOR = 1.76, p = 0.035) independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery (aHR = 2.17, p

Background: Few studies have evaluated in pregnant women with HIV the prevalence of smoking and its associations with maternal and neonatal outcomes. Objectives: to assess the prevalence of smoking among women with HIV in early pregnancy and the association between smoking and pregnancy outcomes in this particular population. Methods: We used data from a multicenter observational study to define the prevalence of smoking in women with HIV in early pregnancy, and the role of smoking status and intensity as risk factors for adverse maternal and neonatal outcomes. Main outcome measures were fetal growth restriction [FGR], preterm delivery [PD] and low birthweight [LB], evaluated in univariate and multivariate analyses. Results: The overall (2001-2018) prevalence of reported smoking (at least one cigarette/day) was 25.6% (792/3097), with a significant decrease in recent years (19.0% in 2013-2018). Women who smoked were less commonly African, had lower body mass index, older age, a longer history of HIV infection and higher CD4 counts. In univariate analyses, smokers were significantly more likely to have PD, LB, FGR and detectable HIV viral load at third trimester. Multivariable analyses confirmed for smokers a significantly higher risk of LB (adjusted odds ratio [AOR]: 1.69, 95%CI 1.22-2.34) and FGR (AOR 1.88, 95%CI 1.27-2.80), while the associations with detectable HIV and PD were not maintained. Conclusions: The common prevalence of smoking among pregnant women with HIV and its association with adverse outcomes indicates that smoking cessation programs in this population may have a significant impact on neonatal and maternal health.

BackgroundCongenital cytomegalovirus (cCMV) infection is the most frequent non-genetic cause of sensorineural hearing-loss (SNHL) (i.e., hearing loss due to a cochlear and/or auditory nerve damage). It is widely accepted that SNHL at birth, when associated to cCMV symptomatic infection involving the central nervous system, benefits from antiviral therapy started in the neonatal period. Conversely, there is no consensus for antiviral treatment in congenitally infected infants diagnosed with isolated SNHL (i.e., SNHL in an otherwise asymptomatic infant) at birth.Our aim was to assess the frequency and the auditory outcome of isolated SNHL at birth due to auditory neuropathy (AN) (i.e., SNHL in a patient with normal cochlear function and auditory nerve dysfunction) in infants with cCMV infection.MethodsWe retrospectively reviewed the clinical history of 60 infants, born at term, with cCMV asymptomatic infection, without additional risk factors for SNHL, and exhibiting bilateral “pass” otoacustic emissions (OAE). None of them underwent antiviral therapy.Hearing thresholds were assessed by means of Auditory Brainstem Responses (ABR). AN affected children were followed up until possible normalization of the hearing thresholds or definitive diagnosis of AN. Each infant diagnosed with monolateral or bilateral AN was classified according to the worst ear threshold.ResultsIn our population, the first ABR was performed at a mean age of 5.00 ± 2.79 (SD) months and AN was diagnosed in 16/60 (26.67%) infants; in 4 infants the AN was defined as mild (4/4 monolateral), moderate in 11 (5/11 bilateral), and severe in 1 (bilateral). The mean age at first ABR was 3.69 ± 2.80 (SD) months in the 16 babies with AN and 5.48 ± 2.66 (SD) months in the 44 infants with normal hearing (p = 0.007). All AN cases spontaneously recovered a normal auditory threshold over time. The mean length of the audiological follow-up was 32.44 ± 17.58 (SD) months (range 5–60 months).ConclusionA delayed maturation of the auditory pathways should be considered when a mild/moderate isolated AN at birth is detected in cCMV infected infants. Prospective studies conducted on larger populations, and with a longer audiological follow-up, are needed to confirm our findings.

Listeriosis is an uncommon foodborne infection that may cause moderate maternal illness, but can be extremely serious for the fetus and the newborn. Several guidelines have been elaborated in order to help clinicians on the care of pregnant women with known or suspected exposure to Listeria monocytogenes. The aim of this review is to collect, assess and summarize them, in order to provide a comprehensive overlook and to highlight the grey areas in the guidance that could result in failure to detect some infected but asymptomatic women. Areas covered: A literature review was performed to provide an update on listeriosis infections, with a greater focus on diagnosis and management of pregnancy-related cases. Expert commentary: Since pregnancy-associated listeriosis causes potentially fatal consequences, it is important that healthcare providers recognize earlier symptoms, diagnosis methods and treatment of the infection. Listeriosis could be asymptomatic and/or a pregnant woman could not be aware of being exposed to Listeria, therefore a serological test is suggested to detect the presence of anti-listeriolysin O antibodies in blood. Finally, a final flowchart is proposed that could improve the early diagnosis of the infection in pregnant women.

The impact of baseline HIV-1 reverse transcriptase (RT) polymorphisms on response to first-line modern HAART containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) was evaluated. The impact of each RT polymorphism on virological success (VS) was evaluated in 604 HIV-1 subtype B-infected patients starting TDF+FTC-containing HAART. TDF and FTC antiviral activity was also tested in PBMCs infected by mutagenised HIV. Structural analysis based on docking simulations was performed. A98S was the only mutation significantly correlated with an increased proportion of patients achieving VS at 24 weeks (94.0% vs. 84.3%; P=0.03). Multivariate regression and Cox model analyses confirmed this result. At concentrations close to the minimal concentration achieved in patient plasma, TDF and FTC exhibited higher potency in the presence of A98S-mutated virus compared with wild-type (IC90,TDF, 8.6±1.1 vs. 19.3±3.5nM; and IC90,FTC, 12.4±7.7 vs. 16.8±9.8nM, respectively). The efficacy of FTC, abrogated by M184V, was partially restored by A98S (IC90,FTC, 5169±5931nM for A98S+M184V vs. 18477±12478nM for M184V alone). Docking analysis showed the higher potency of TDF and FTC in the presence of A98S-mutated virus was mainly due to higher binding affinity between drugs and mutated RT compared with wild-type. In the presence of FTC, A98S also partially restored the RT binding affinity impaired by M184V alone. A98S polymorphism improves virological response to TDF+FTC-containing HAART. This may help clinicians in the choice of the optimal NRTI backbone aimed at achieving maximal virological inhibition.

The Zika virus (ZIKV) genome, its negative-strand viral proteins, and virus-like particles were detected in placenta-derived mesenchymal cells (MSCs), indicating that ZIKV persists after virus clearance from maternal blood and can be rescued by in vitro cultivation. We report for the first time the presence of replication-competent ZIKV in MSCs from an asymptomatic woman who acquired infection during pregnancy., Replication-competent ZIKV was rescued from placenta-derived mesenchymal cells (MSCs), isolated from a woman who acquired the infection during pregnancy, cleared viremia and delivered a newborn with no signs of infection. Our findings suggest a possible role of placental MSCs as ZIKV reservoir in vertical transmission.

Congenital malaria (CM) is uncommon in both malaria-endemic and non-endemic countries. It may be caused by any Plasmodium spp., although Plasmodium falciparum and Plasmodium vivax are the more frequent etiologic agents. We report a case of delayed diagnosis of CM by P. vivax in a newborn of an Eritrean primigravida. The mother developed pregnancy-related immunodepression and varicella-zoster viral infection 9 days before natural delivery; therefore, the child was admitted in the neonatal intensive care unit (NICU) to administer specific varicella-zoster immunoglobulin prophylaxis and for clinical monitoring. During the NICU stay, the newborn presented a febrile syndrome with vomiting, anemia, and thrombocytopenia. A P. vivax severe malaria diagnosis was made by detecting trophozoites in the thick and thin blood smears. The infant was successfully treated with intravenous artesunate and clindamycin. Our experience suggests that malaria diagnostic tests need to be included in routine blood analyses in newborns with febrile syndrome from mothers with an epidemiologic link to malaria-endemic areas.

As asymptomatic infections represent 80% of ZIKV-infected individuals, sexual transmission is a rising concern. Recent studies highlighted a preferential association of ZIKV with the cellular fraction (CF) of different specimen types. Our aim was to evaluate the presence of ZIKV-RNA in different body fluids, focusing on semen specimens to assess the ZIKV-RNA content in either the unfractionated sample, its CF or seminal plasma (SP). In addition, to establish if the presence of ZIKV genome was associated with active virus replication, we measured the levels of negative-strand ZIKV-RNA. ZIKV total-RNA was detected in blood, urine and unfractionated semen, and neg-RNA in semen CF and SP samples longitudinally collected from two ZIKV-positive men followed at the National Institute for Infectious Diseases "L. Spallanzani", Italy. In both patients, ZIKV total-RNA was detected in CF with ct values always lower than in the corresponding unfractionated samples, and was observed even in the CF from negative unfractionated semen samples. In Patient 2, neg-RNA was also detected in CF, suggesting ongoing viral replication. Our results demonstrate higher clinical sensitivity of CF as compared to whole semen testing, emphasizing the need to extend ZIKV-RNA testing to CF, to rule out virus presence and the possible risk of sexual transmission.

Congenital malaria (CM) is uncommon in both malaria-endemic and non-endemic countries. It may be caused by any Plasmodium spp., although Plasmodium falciparum and Plasmodium vivax are the more frequent etiologic agents. We report a case of delayed diagnosis of CM by P. vivax in a newborn of an Eritrean primigravida. The mother developed pregnancy-related immunodepression and varicella-zoster viral infection 9 days before natural delivery; therefore, the child was admitted in the neonatal intensive care unit (NICU) to administer specific varicella-zoster immunoglobulin prophylaxis and for clinical monitoring. During the NICU stay, the newborn presented a febrile syndrome with vomiting, anemia, and thrombocytopenia. A P. vivax severe malaria diagnosis was made by detecting trophozoites in the thick and thin blood smears. The infant was successfully treated with intravenous artesunate and clindamycin. Our experience suggests that malaria diagnostic tests need to be included in routine blood analyses in newborns with febrile syndrome from mothers with an epidemiologic link to malaria-endemic areas.

Background HIV genetic diversity implicates major challenges for the control of viral infection by the immune system and for the identification of an effective immunotherapeutic strategy. With the present case report we underline as HIV evolution could be effectively halted by early antiretroviral treatment (eART). Few cases supported this evidence due to the difficulty of performing amplification and sequencing analysis in long-term viral suppressed patients. Here, we reported the case of limited HIV-1 viral evolution over time in a successful early treated child. Case presentation A perinatally HIV-1 infected infant was treated within 7 weeks of age with zidovudine, lamivudine, nevirapine and lopinavir/ritonavir. At antiretroviral treatment (ART) initiation HIV-1 viral load (VL) and CD4 percentage were >500,000 copies/ml and 35%, respectively. Plasma genotypic resistance test showed a wild-type virus. The child reached VL undetectability after 33 weeks of combination antiretroviral therapy (cART) since he maintained a stable VL 90%). Any major evolutionary divergence was detected. Conclusions eART limits the viral evolution avoiding the emergence of new viral variants. This result may have important implications in host immune control and may sustain the challenge search of new personalized immunotherapeutic approaches to achieve a prolonged viral remission. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-2092-z) contains supplementary material, which is available to authorized users.

Background: There is limited information on pregnancy loss in women with HIV, and it is still debate whether HIV-related markers may play a role. Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease. Methods: Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (

A man in his early 30s reported in January 2016 a history of fever, asthenia and erythematous rash during a stay in Haiti. On his return to Italy, ZIKV RNA was detected in his urine and saliva 91 days after symptom onset, and in his semen on day 188, six months after symptom onset. Our findings support the possibility of sexual transmission of ZIKV and highlight the importance of continuing to investigate non-vector-borne ZIKV infection.

Although HIV-associated neurocognitive disorders should be treated with highly active antiretroviral treatment (HAART) regimens with good central nervous system (CNS) penetration, the definition of neuroactive HAART remains controversial. We compared 2 ranking systems to measure HAART neuroeffectiveness.Patients with (n = 93) or at risk for (n = 92) HIV-associated neurocognitive disorders underwent neuropsychological (NP) test batteries before HAART initiation and at follow-up. Changes in normatively adjusted summary NP test z scores were calculated for each subject. Two neuropenetration scores were calculated: the central nervous system penetration reference score (number of drugs in the combination among zidovudine, abacavir, stavudine, lamivudine, efavirenz, nevirapine, indinavir, and lopinavir-ritonavir) and the CNS penetration-effectiveness (CPE) score: a summary score of 1 (high: penetration: [corrected] zidovudine, abacavir, delavirdine, [corrected] nevirapine, amprenavir-ritonavir, fosamprenavir-ritonavir, [corrected] indinavir-ritonavir, and lopinavir-ritonavir), 0.5 (intermediate penetration: [corrected] stavudine, lamivudine, emtricitabine, efavirenz, amprenavir, fosamprenavir, [corrected] atazanavir-ritonavir, atazanavir, [corrected] and indinavir), and 0 (low penetration: remaining ARVs) [corrected] for each drug in the combination. Main outcome measures were changes in global NPZ scores and in summary z scores on 5 domains.At regression analyses, higher CPE scores correlated with greater improvements in NPZ-4 (P = 0.0283), NPZ-8 (P = 0.0071), concentration and speed of mental processing (P = 0.0046), and mental flexibility (P = 0.0262) summary z scores. The correlation was stronger among NP-impaired patients. By contrast, higher estimates of neuroeffectiveness with the alternative system showed no correlation. No association was seen between CD4 and plasma viral load changes with both scores.The CPE score represents a step forward toward the identification of a clinically useful approach to estimating HAART ability to improve cognition.

Among 469 women with a diagnosis of HIV in pregnancy, 74 (15.8%) presented with less than 200 CD4 cells per cubic millimeter. The only variable significantly associated with this occurrence was African origin (odds ratio: 2.22, 95% confidence intervals: 1.32 to 3.75, P = 0.003). Four women with low CD4 (5.6%), compared with none with higher CD4 counts, had severe AIDS-defining conditions (P < 0.001) during pregnancy or soon after delivery, and one transmitted HIV to the newborn. Early preterm delivery (

Currently, there is no evidence whether ganciclovir, or its oral prodrug valganciclovir, penetrates into the cerebrospinal fluid of human infants treated for congenital cytomegalovirus infection. Here, we report a case study providing evidence that ganciclovir, administered as valganciclovir, reaches the infant’s cerebrospinal fluid when used at the currently recommended dose for congenital cytomegalovirus infection.

A cluster of HIV-1 infection has been identified in Libya in 1999, involving 402 children admitted to "El-Fath" Children's Hospital in Benghazi (BCH) during 1998 and 19 of their mothers. Nosocomial transmission has been indicated as responsible for the spread of infection. Out of this group, 104 children and 19 adult women have been followed at the National Institute for Infectious Diseases L. Spallanzani in Rome during 1 year. At BCH, all children had received intravenous infusions but not blood or blood products. A single child receiving a blood transfusion in 1997 and the 17 infected mothers were never hospitalized in Benghazi. In addition, two nurses were diagnosed as HIV-1 infected. In 40 subjects out of this group HIV-1 gag, env, and pol fragments were amplified and sequenced. The phylogenetic analyses showed that a monophyletic recombinant HIV-1 form CRF02-AG was infecting all of the HIV-1-seropositive patients admitted at BCH with no close similarities to the other CRF02-AG reported to GenBank. A different strain was found in the child infected by blood transfusion. The data thus suggest a highly contagious nosocomial spread of HIV-1 infection and possibly transmission of the virus from child to mother during breastfeeding in connection with primary HIV-1 infection.

BACKGROUND Haematopoietic progenitor cells (HPC) of HIV-1-infected patients are severely compromised in their replication and clonogenic capacities, and show an enhanced propensity to apoptosis, despite the lack of productive or latent HIV-1 infection. OBJECTIVE To investigate telomerase enzyme levels in CD34+ HPC isolated from HIV-1-infected patients, because the absence of telomerase activity has been found to be correlated with a diminished replication potential. METHODS Telomerase levels were measured by a PCR-based telomeric repeat amplification protocol. CD34+ HPC isolated from the peripheral blood of 11 HIV-1-infected patients were compared with CD34+ HPC isolated from peripheral blood (nine subjects) or bone marrow (six subjects) from 15 healthy donors. Telomerase levels were also studied in normal HPC after exposure to either gp120 or transforming growth factor (TGF)-beta1. RESULTS CD34+ HPC isolated from either peripheral blood or bone marrow from healthy donors expressed a high level of telomerase activity. On the contrary, CD34+ HPC isolated from HIV-1-seropositive patients did not express any detectable telomerase activity in nine patients, and a clearly reduced enzymatic activity in two patients. Furthermore, telomerase activity in normal CD34+ HPC exposed to recombinant gp120 was significantly reduced, and to a higher extent than in CD34+ HPC exposed to recombinant TGF-beta1. CONCLUSIONS This is the first study to demonstrate severely impaired telomerase activity in uninfected CD34+ HPC isolated from HIV-1-infected patients. The mechanism underlying this impairment probably involves the interaction of HIV-1 envelope glycoprotein gp120 with the cell membrane. These results may add to our understanding of the pathogenesis of the lesion of the HPC compartment.

Objective: To evaluate the role of the selective forces exerted by the host on the HIV-1 structures involved in viral entry. Design and methods: The V3 region of the env gene was analysed in cell-free HIV-1 RNA from 17 infected subjects: 11 long-term non-progressors (LTNP) and six symptomless, typical progressor patients. To evaluate the potential biological significance of one of the rare variants detected in the LTNP, it was reproduced by recombinant PCR into a HIV-1 molecular clone. Results: The intrapatient divergence of the V3-loop sequences averaged 8.62% in LTNP and 5.29% in progressors, although LTNP displayed lower divergence from the clade B consensus than progressors (16.65 and 19.76%, respectively). The analysis of non-synonymous and synonymous substitutions indicated that selective pressure was exerted in this region in both LTNP and progressors. Individual peculiarities (unique and rare V3-loop variants) emerged, however, in most sequences from LTNP, and variants bearing mutations in a domain crucial for the V3-loop structure were more prevalent in LTNP (P = 0.0012). The pNL4-3-derived mutant reproducing a V3-loop variant detected in a LTNP was efficiently expressed upon transfection, but the mutant virus was nearly completely unable to infect CD4+ cell lines, activated primary peripheral blood lymphocytes, or monocyte-derived macrophages, suggesting that a defect impaired the entry phase of the replication cycle. Conclusions: The results indicate that host factors impose selective constraints on the evolution of the HIV-1 structures involved in viral entry. In LTNP, these factors are likely to force the virus into attenuated variants.

The objective of the study was to evaluate the access to Papanicolau (Pap) tests of HIV-infected women in Italy. A cross-sectional survey on a cohort of HIV-infected women seen at 27 HIV clinics was performed. At each clinic a female physician involved in the care of HIV-infected women was asked questions on clinic and patients' characteristics and on access to Pap tests. The outcome of the study was to find the percentage of women who had not had a Pap test before coming to the HIV clinic and the percentage having had a Pap test in 2001. In the survey, 7,600 HIV-infected women were represented. Women who came to the clinic without having ever had a Pap test were 62+/-22%, while women who had had a Pap test in 2001 were 43+/-36%. Women who reported never having had a Pap test before coming to the HIV clinic were more often from the south than the north of Italy (17.9+/-49% from the north, 18+/-53% from the center and 9.3+/-83.9% from the south; p0.001). This a difference disappeared when comparing the women who had had a Pap test in 2001 (28+/-39.6% from the north, 31.6+/-44.2% from the center and 25.6+/-45.7% from the south; p=0.88). Despite the published guidelines in Italy, only 38% of women had ever had a Pap test before coming to the HIV clinic and only 43% had had a Pap test in 2001. Strategies aimed to improve these proportions should be rapidly implemented at all levels of care organization.

TO THE EDITORS: We read with great interest the article by Semprini et al 1 concluding that semen washing with intrauterine insemination (SW-IUI) appears to be a safe and effective method for achieving pregnancy in human immunodeficiency virus (HIV)-discordant couples in which the man is HIV infected. However, the authors did not discuss some of the problems that render SW-IUI not practicable for most couples in developed countries, and the current debate on different options. SW-IUI is cumbersome and costly, per-cycle live birth rate is 13%, and for a significant number of couples, the wish of parenthood remained unaccomplished due to the technical and financial hurdles associated with the method. Approximately 30% of couples evaluated in Milan, Italy, and St Gallen, Switzerland, did not start the insemination process after initial counseling and another 30% subsequently withdrew after a number of failed cycles. Moreover, almost half of the couples who did not conceive with artificial insemination attempted spontaneous conception through unprotected intercourse, exposing the woman to HIV transmission, and at least 1 infection occurred. 1,2

There is limited information on pregnancy outcomes in women with HIV who are of a more advanced maternal age.Data from a national observational study in Italy were used to evaluate the risk of nonelective cesarean section, preterm delivery, low birthweight, major birth defects, and small gestational age-adjusted birthweight according to maternal age (35 and ≥35 years, respectively).Among 1,375 pregnancies with live births, 82.4% of deliveries were elective cesarean sections, 15.8% were nonelective cesarean sections, and 1.8% were vaginal deliveries. Rates of nonelective cesarean section were similar among mothers ≥35 and35 years (odds ratio [OR], 1.22; 95% CI, 0.90-1.65;P = .19). Preterm delivery and low birthweight were significantly more common among women ≥35 years in univariate but not in multivariate analyses. Newborns from women ≥35 and35 years showed no differences inZ scores of birthweight, with a similar occurrence of birthweight10th percentile (12.1% vs 12.0%; OR, 1.02; 95% CI, 0.71-1.46;P = .93). The overall rate of birth defects was 3.4% (95% CI, 2.4-4.4), with no differences by maternal age (≥35 years, 3.5%;35 years, 3.3%; OR, 1.05; 95% CI, 0.56-1.98;P = .88).In this study of pregnant women with HIV, older women were at higher risk of some adverse pregnancy outcomes, such as preterm delivery and low birthweight. The association, however, did not persist in multivariable analyses, suggesting a role of some predisposing factors associated with older age.

Background HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naïve to antiretrovirals. Methods Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected. Results Drug-resistance analysis was performed on 97 naïve infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes. Conclusion Our study reports an 11.9% prevalence rate of primary drug resistance in naïve HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up.

To evaluate the incidence of Toxoplasma gondii infection, the detection of specific IgG, IgM, IgA and IgG avidity was performed on 1424 pregnant women referred to the “L. Spallanzani” Hospital in Rome (Italy). Of the 1424 women screened, 20 (1.40%) were likely to have been recently infected (presence of IgM/IgA, and/or low IgG avidity), 29 (2.04%) had positive IgM coupled with high IgG avidity, 7 (0.49%) had an unspecific result for IgM alone, 1339 (94.0%), were negative for both IgG and IgM, 29 (2.04%) showed evidence of past infection (IgG positive, IgM negative, high IgG avidity). In Conclusion our results underscore the importance of efficient antenatal screening and appropriate treatment for Toxoplasma infection in Italy.

Pregnancy has been associated with a low risk of HIV disease progression. Most pregnancies with HIV currently involve women who have not experienced AIDS-defining events, and are clinically classified as Centers for Disease Control and Prevention (CDC) groups A or B. We evaluated the main maternal outcomes among pregnant women with more advanced HIV disease, defined by CDC-C disease stage. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. A total of 566 HIV-infected mothers, 515 in stage A or B (CDC-AB group) and 51 in stage C (CDC-C group) were evaluated. The two groups had similar baseline characteristics. No differences were found in the main maternal and neonatal outcomes. Most of the women achieved viral suppression at end of pregnancy (>1000 copies per milliliter: CDC-C: 17.2%; CDC-AB: 13.7%). One year after delivery, HIV replication (HIV-RNA >1000 copies per milliliter) was present in 11.5% of CDC-AB women and 30.0% CDC-C women. Despite lower initial CD4 counts (300 versus 481 cells per microliter), CDC-C women maintained stable CD4 levels during pregnancy, and 1 year after delivery, a significant increase in CD4 count from preconception values was observed in both groups (CDC-C: +72 cells per microliter, p=0.031; CDC-AB: +43 cells per microliter, p

BACKGROUND: There is limited information on the relation between glucose levels in pregnancy and adverse perinatal outcomes in HIV-infected pregnant women. OBJECTIVE: To evaluate the potential impact of fasting glucose levels on pregnancy outcomes in a large sample of pregnant women with HIV from a national study, adjusting for potential confounders. METHODS: Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. The main outcomes evaluated in univariate and multivariable analyses were birthweight for gestational age>90th percentile (large for gestational age [LGA]), nonelective cesarean delivery, and preterm delivery. Glucose measurements were considered both as continuous and as categorical variables, following the HAPO study definition. RESULTS: Overall, 1,032 cases were eligible for the analysis. In multivariable analyses, a birthweight>90th percentile was associated with increasing fasting plasma glucose levels (adjusted odds ratio [AOR] per unitary (mg/dL) increase, 1.04; 95% CI, 1.01-1.06; P=.005), a higher body mass index, and parity of 1 or higher. A lower risk of LGA was associated with smoking and African ethnicity. A higher fasting plasma glucose category was significantly associated with LGA occurrence, and AORs for the glucose categories of 90-94 mg/ dL and 95-99 mg/dL were 3.34 (95% CI, 1.09-10.22) and 6.26 (95% CI, 1.82-21.58), respectively. Fasting plasma glucose showed no association with nonelective cesarean section [OR per unitary increase, 1.00; 95% CI, 0.98-1.02] or preterm delivery [OR per unitary increase, 1.00; 95% CI, 0.99-1.02]. CONCLUSIONS: In pregnant women with HIV, glucose values below the threshold usually defining hyperglycemia are associated with an increased risk of delivering LGA infants. Other conditions may independently contribute to adverse perinatal outcomes in women with HIV and should be considered to identify pregnancies at risk.

It has long been recognized that drug metabolism and drug toxicity may vary greatly between individuals, affecting both efficacy and toxicity. Pharmacogenetics could benefit HIV therapeutics because of the high prevalence of drug-related adverse events and the long term nature and complexity of combination therapy. In recent years a number of associations between human genetic variants and predisposition to drug toxicity and risk of virologic failure have been described. This review summarizes the existing literature on pharmacogenetic determinants of antiretroviral drug exposure, toxicity, and activity. Studies across the world have consistently demonstrated that HLA-B*5701 predicts the likelihood of hypersensitivity reactions to abacavir. As a consequence, pharmacogenetic screening for HLA-B*5701 has entered routine clinical practice and is recommended in most guidelines before starting an abacavir containing regimen. Moreover, prospective clinical trials and cohort studies have identified a number of associations between human genetic variants, drug metabolism and toxicity. These include nevirapine hypersensitivity and hepatotoxicity, efavirenz plasma levels and central nervous system side effects, indinavir- and atazanavir-associated hyperbilirubinemia, antiretroviral drug-associated peripheral neuropathy, lipodystrophy and hyperlipidaemia, NRTI-related pancreatitis, and tenofovir-associated renal proximal tubulopathy. Thus, pharmacogenetics is expected to play an important role in HIV treatment in the near future. The aim of the present paper is to provide HIV clinicians with a comprehensive review of recent achievements and future prospects for HIV pharmacogenetics.

Early recognition of virologic failure in patients with extensive drug resistance receiving salvage-HAART is essential to avoid exposure to subinhibitory regimens. We studied plasma viral load (PVL) decline and rates of drug-resistance mutation (DRM) accumulation in such patients. A prospective, 48 week study of 38 heavily pretreated patients receiving genotypic resistance testing (GRT)-guided HAART was conducted. The rate of PVL decline was studied by weekly PVL determinations. To assess DRM accumulation, serial GRTs were performed in all nonresponders (never reaching PVL50 or two PVLs50 copies/ml after suppression). Over 48 weeks, 10 patients (26%) were nonresponders. Receiving less then two fully active drugs and having an elevated number of PI and NRTI mutations at baseline were strongly associated with virologic failure. There was no evidence of a difference in the change from baseline PVL to week 1 and 2 between responders and nonresponders. By contrast, PVL reductions from week 2 to week 3 and thereafter were significantly greater for responders (p0.01). Among nonresponders, the incidence rates per patient-month (95% CI) of emergent DRM were 0.67 (0.13-1.20), 0.40 (0.00-0.74), and 0.37 (0.00-0.75) at weeks 4, 8, and 24, respectively. Having limited baseline resistance, receiving at least two fully active drugs, and showing constant PVL reductions from week 2 to week 3 and thereafter were predictive of virologic response. In contrast, early changes in PVL levels were not. Virologic failure was associated with detection of emergent DRMs. Virologic rebound in patients on salvage-HAART should be addressed aggressively.

A case report of dual sexual transmission, with secondary transmission from naïve to naïve patient, of HIV harbouring K103N and L100I mutations, conferring full non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, plus 2 nucleoside analogous reverse transcriptase inhibitor (NRTI) mutations is described. The secondary transmission of the resistant virus was confirmed by phylogenetic analysis. Data also suggest that mutations related to NRTI and NNRTI resistance may persist for a long time in naive patients, over 2 years in the present case report.

Emtricitabine FTC is a cytosine analogue, recently introduced in clinical practice for the treatment of HIV patients. In order to evaluate the safety and efficacy of antiretroviral regimen containing emtricitabine in the clinical practice, we performed an observational study on all patients starting a regimens containing emtricitabine in a clinical unit. Data were collected from clinical charts and inserted into a computerized database. We evaluated the following outcome measures: probability of interruption of FTC-regimen due to side effects; time to virologic suppression in patients with detectable viral load at baseline; time to loss of virologic efficacy in patients with virologic suppression at baseline, immunologic variations. In the period January 2005- March 2006, overall 150 patients started a FTC-regimen; 16.7% of them were naïve to antiretroviral treatment. The median period of observation was 80 days (IQR 26-190) and 26.7% of patients had a longitudinal observation longer than 24 weeks. At last observation, 82% of patients were still continuing baseline regimen and 13.3% interrupted FTC. Efficacy analysis in viremic patients showed that 6 months-probability of virologic success during treatment with FTC was 74.7%. Our preliminary observation show that FTC-regimens seems effective and tolerable in real practice.

The emergence of HIV-resistant strains generally occurs during treatment failure. A high rate of viral replication, low patient adherence to therapy, poor drug absorption or increased drug metabolism may be related to treatment failure and favour the onset of resistance. Recently, despite the absence of detectable HIV viral load in plasma, the importance of the persistence of HIV replication in other reservoirs has been underlined. Paired semen and plasma specimens stored from HIV male patients were tested using the LiPA assay, detecting genotype mutations related to Nucleoside Reverse Transciptase Inhibitors (NRTI) resistance. Overall, 32 paired semen and plasma samples were analyzed. The presence of HIVsequences was determined in 13 paired specimens (40.6%). Sixteen semen and 10 plasma specimens failed to amplify. At least one mutation was identified in the plasma of 77.8% of treated and 50.0% of naive patients. Similarly, mutations were identified in the semen of 66.7% of treated and 50.0% of untreated patients. Different mutation patterns between the two compartments were found in 46.2% of patients. The use of rapid assessment of HIV resistance in plasma and semen may be useful in some situations, such as HIV infection transmitted by sexual contact. Our data reinforce the evidence that, regarding HIV replication, the male genital tract must be considered as a separate compartment from the plasma.

Single witness: HIV-1 drug resistance assays have been shown to be of value for guiding antiretroviral therapy (ART) decisions. Different tissues or body fluids in which HIV-1 can reside may contain viruses with distinct characteristics. HIV-1 variants with genotypic resistance markers are present in the male genital tract and evolve over time on incompletely suppressive ART. The magnitude of decline in the semen HIV-RNA level in with therapy is usually similar to the effect of treatment on the blood viral burden. Not all men on ART have complete suppression of HIV-1 replication in genital tract; thus, they may shed resistant HIV-1 strains. Failure of treatment to suppress HIV-RNA levels in the blood is common, resulting in the selection of resistant HIV-1 variants. Sexual transmission of resistant variants may have a negative impact on treatment outcome in newly infected individuals and on the spread of the diseases within a population. The use of rapid assessment of HIV resistance in plasma and semen may be useful in some situations, e.g. HIV transmitted infection by sexual contact from a viraemic patient. The recognition of resistant HIV isolates in the blood and semen of patients receiving ART leads to the question of the potential role of resistance testing. In many but not all infectious diseases, the choice of therapy is guided by sensitivity testing. Recent data suggest that testing the drug sensitivity of viral isolates from the blood can benefit patient management and response to therapy, albeit at considerable cost. However, since drug resistance may evolve independently in blood and semen, the public health benefits of such testing are unproven.

Defects in the apoptotic pathway represent a critical element in the progression of neoplastic disease and may also concur to determine treatment efficacy at the cellular level. Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling. In this study we analyzed, by immunohistochemistry, the expression of Fas protein in a group of 68 NSCLC (non-small cell lung cancer) specimens. Statistical analyses did not show any significant relationship between Fas immunohistochemical expression and clinical parameters of lung cancer patients, except for nodal status. Our data do not support the use of Fas as a molecular prognostic role in NSCLC. On the other hand, considering the role of the Fas-pathway in chemotherapy-induced apoptosis, further studies are required to analyze the potential value of Fas expression in predicting the response of NSCLC patients to chemotherapy.

We report the case of a young man, with a previous history of parenteral drug abuse, who developed a Weber's syndrome. Brain computed tomographic scan and nuclear magnetic resonance imaging showed a single ring enhancing lesion in the right mesencephalic site. After the demonstration of seropositivity for human immunodeficiency vims, a presumptive diagnosis of cerebral toxoplasmosis in an AIDS patient was made and a specific treatment was started. A partial neuroradiological and clinical improvement were obtained. Opportunistic cerebral lesions, as first manifestation of AIDS, should be always considered in subjects at risk for AIDS who present a brainstem syndrome.