Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals

Despite multiple sexual exposure to HIV-1 virus, some individuals remain HIV-1 seronegative (exposed seronegative, ESN). The mechanisms underlying this resistance remain still unclear, although a multifactorial pathogenesis can be hypothesised. Although several genetic factors have been related to HIV-1 resistance, the homozigosity for a mutation in CCR5 gene (the 32 bp deletion, i.e. CCR5-Delta32 allele) is presently considered the most relevant one. In the present study we analysed the genotype at CCR5 locus of 30 Italian ESN individuals (case group) who referred multiple unprotected heterosexual intercourse with HIV-1 seropositive partner(s), for at least two years. One hundred and twenty HIV-1 infected patients and 120 individuals representative of the general population were included as control groups. Twenty percent of ESN individuals had heterozygous CCR5-Delta 32 genotype, compared to 7.5% of HIV-1 seropositive and 10% of individuals from the general population, respectively. None of the analysed individuals had CCR5-Delta 32 homozygous genotype. Sequence analysis of the entire open reading frame of CCR5 was performed in all ESN subjects and no polymorphisms or mutations were identified. Moreover, we determined the distribution of C77G variant in CD45 gene, which has been previously related to HIV-1 infection susceptibility. The frequency of the C77G variant showed no significant difference between ESN subjects and the two control groups. In conclusion, our data show a significantly higher frequency of CCR5-Delta 32 heterozygous genotype (p = 0.04) among the Italian heterosexual ESN individuals compared to HIV-1 seropositive patients, suggesting a partial protective role of CCR5-Delta 32 heterozygosity in this cohort

Older age does not influence CD4 cell recovery in HIV-1 infected patients receiving Highly Active Anti Retroviral Therapy

BACKGROUND: Diagnosis of HIV infection is recently occurring with increasing frequency in middle-aged and in older individuals. As HAART became available, a minimal beneficial effect on immunological outcome in older in respect of younger subjects has been reported. In fact, both the intensity and the rapidity of the immunological response appeared to be reduced in elderly subjects. On the contrary, only few reports have indicated a similar immunological outcome both in older and younger HIV-positive subjects. Interestingly, older age did not seem to significantly affect the long-term virological outcome of HAART treated subjects. METHODS: To characterise epidemiological and clinical features of older HIV+ subjects, a prospective case-control study was performed: 120 subjects ≥ 50 and 476 between 20 and 35 years were initially compared. Subsequently, to better define the impact of HAART on their viro-immunological response, 81 older were compared with 162 younger subjects. RESULTS: At baseline cases presented significantly lower TCD4+ cell number and were more frequently affected by comorbid conditions. Under HAART a statistically significant increase in TCD4+ cell number was observed in cases and controls. At multivariate analysis, there was no statistically significant difference between cases and controls regarding viro-immunological response. CONCLUSIONS: Although older subjects present a more severe HIV infection, they can achieve, under HAART, the same viro-immunological success as the younger individuals

Is "option B+" also being adopted in pregnant women in high-income countries? Temporal trends from a national study in Italy

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Antiretroviral treatment in pregnancy: a six-years perspective on recent trands in prescription patterns, viral load suppression, and pregnancy outcomes.

The aim of the study was to describe the recent trends in antiretroviral treatment in late pregnancy and the sociodemographic changes among pregnant women with HIV over the last 6 years. Data from the National Program on Surveillance on Antiretroviral Treatment in Pregnancy in Italy were grouped per calendar year, and changes in antiretroviral treatment, population characteristics, maternal immunovirologic status and newborn clinical parameters were analyzed. A total of 981 HIV-infected mothers who delivered between 2002 and 2008 were evaluated. The proportion of women receiving at least three antiretroviral drugs at delivery increased significantly from 63.0% in 2002 to 95.5% in 2007-2008, paralleled by a similar upward trend in the proportion of women who achieved complete viral suppression at third trimester (from 37.3 in 2002 to 80.9 in 2007-2008; p < 0.001). The co-formulation of zidovudine plus lamivudine remained the most common nucleoside backbone in pregnancy, even if a significant increase in the use of tenofovir plus emtricitabine was observed in more recent years. Starting from 2003, nevirapine prescription declined, paralleled by a significant rise in the use of protease inhibitors (PI), which were present in more than 60% of regimens administered in 2007-2008. Nelfinavir was progressively replaced by ritonavir-boosted PIs, mainly lopinavir. No significant changes in preterm delivery, Apgar score, birth weight, and birth defects were observed during the study period, and the rate of HIV transmission remained below 2%. These data demonstrate a significant evolution in the treatment of HIV in pregnancy. Constant improvements in the rates of HIV suppression were observed, probably driven by the adoption of stronger and more effective regimens and by the increasing options available for combination treatment

Hematological effects of zidovudine prophylaxis in newborn infants with and without prenatal exposure to zidovudine

Postnatal prophylaxis with oral zidovudine (ZDV) is associated with hematological effects. However, it is still unknown whether selection of non-ZDV-based regimens in pregnancy may reduce hematological toxicity associated with postnatal ZDV prophylaxis. The aim of this study was to define the hematological effects of ZDV prophylaxis in newborns with and without prenatal exposure to ZDV. Sixty-five newborns from mothers infected with HIV who, during pregnancy, received HAART regimens with (n:44) and without (n:21) ZDV were evaluated. Virological and hematological data were compared at birth and at 4 weeks and 6 months of life. Newborns with prenatal ZDV exposure had significantly worse hematological values at birth, with lower levels of hemoglobin (14.3 g/dl vs. 16.2 g/dl, P=0.001), red blood cell count (3.45 × 10(6) cells/mm(3) vs. 4.48 × 10(6) cells/mm(3), P<0.001), and hematocrit (41.0% vs. 46.8%, P<0.001), and higher values of mean corpuscular volume (119 fl vs. 103 fl, P<0.001). The start of ZDV prophylaxis determined significantly greater adverse hematological changes in newborns without prenatal ZDV exposure, and at 4 weeks and 6 months of life the two groups had substantially identical hematological values. The selection of non-ZDV-based regimens in pregnancy does not reduce the final hematological effects of postnatal ZDV at 4 weeks and at 6 months of life. However, two distinct pathways may be observed: newborns exposed prenatally to ZDV have worse hematological values at birth, while newborns without prenatal ZDV exposure have particularly marked postnatal effects. The distinct effects of these two pathways should be considered

Rubella susceptibility profile in pregnant women with HIV

Rubella infection usually has a limited clinical relevance in children and young adults. However, its acquisition during pregnancy may lead to severe fetal or neonatal complications, such as miscarriage, fetal death, or an association of birth defects represented by the congenital rubella syndrome (CRS) [1]. Prevention of CRS through vaccination programs represents a priority in most national and international public health plans, and several countries have implemented vaccination programs aimed at obtaining the World Health Organization (WHO)-recommended target of a CRS incidence below 1 per 100,000 live births per year [2]. There are very limited data on the rubella susceptibility status of human immunodeficiency virus (HIV)-infected pregnant women, and it is still unknown whether this population may be at higher risk of acquiring rubella because of a higher susceptibility prevalence. We used data from a national study to investigate the prevalence of rubella susceptibility in a large series of pregnant women with HIV [3]. Data on susceptibility, assessed through serological testing or personal history, were analyzed with respect to several demographic and HIV-related characteristics. Following exclusion of 93 women with rubella status reported as unknown, 1146 pregnancies with a live birth were analyzed. Overall, between 2001 and 2009, 303 women (26.4%) were reported as susceptible. Among the 843 nonsusceptible women, 163 (19.3%) were reported as previously vaccinated, with a significant increase during the study period in the proportion of vaccinated women, from 3.4% in 2001 to 25.0% in 2009 (χ2 for trend: P  <  .001). During the same period, the proportion of susceptible women decreased significantly, from 26.9% in 2001 (36.2% in 2002) to 18.8% in 2009 (P  =  .002). The general characteristics of susceptible and nonsusceptible women are reported in Table 1. Rubella susceptibility was not associated with any particular HIV-related or demographic characteristic, but appeared to be significantly associated with susceptibility to Toxoplasma infection (odds ratio [OR]: 3.10, 95% confidence interval [CI]: 2.24–4.29, P  <  .001) and with susceptibility to cytomegalovirus (CMV) infection (OR, 6.90; 95% CI, 5.06–9.14; P  <  .001), with a borderline-significance association (P  =  .063) with a negative history of sexually transmitted infections