[show abstract][hide abstract] ABSTRACT: 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<0.001). Only one AIDS event occurred in a woman with a previous diagnosis of AIDS. In CDC-C women, pregnancy is not associated with an increased rate of adverse maternal or neonatal outcomes, and a good immunovirologic response can be expected. During postpartum care, women with more advanced HIV infection should receive particular care to prevent loss of virologic suppression.
AIDS patient care and STDs 09/2011; 25(11):639-45. · 2.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: Simian-human immunodeficiency virus (SHIV) 89.6P is considered to be one of the most pathogenic chimeric viruses in rhesus macaques. However, when crossing from one to another species of monkeys the pathogenicity of this virus may be affected. By using SHIV-89.6P(cy243), a virus obtained by passaging SHIV-89.6P in cynomolgus macaques, we investigated the dynamics of viral replication and the impact of the inoculum size (from 10 up to 50 monkey infectious dose) on the progression of the infection in 22 cynomolgus macaques. SHIV-89.6P(cy243 )caused massive depletion of CD4+ T-cells within 4 weeks of the inoculum, followed by an irreversible immune deficiency in a high proportion of the infected monkeys. This study demonstrates that SHIV-89.6P(cy243) is pathogenic in cynomolgus macaques and that the dynamics of the viral replication and the rate of clinical progression depend on the size of the inoculum. Our findings provide unique and relevant data, particularly with regard to the value of the in vivo titration used to select the most appropriate infectious dose to study the "virus-host" interplay.
Archives of Virology 02/2008; 153(3):463-72. · 2.03 Impact Factor
[show abstract][hide abstract] ABSTRACT: The efficacy of a multicomponent vaccination with modified vaccinia Ankara constructs (rMVA) expressing structural and regulatory genes of simian immunodeficiency virus (SIV(mac251/32H/J5)) was investigated in cynomolgus monkeys, following challenge with a pathogenic SIV. Vaccination with rMVA-J5 performed at week 0, 12, and 24 induced a moderate proliferative response to whole SIV, a detectable humoral response to all but Nef SIV antigens, and failed to induce neutralizing antibodies. Two months after the last boost, the monkeys were challenged intravenously with 50 MID50 of SIV(mac251). All control monkeys, previously inoculated with non-recombinant MVA, were infected by week two and seroconverted by weeks four to eight. In contrast a sharp increase of both humoral and proliferative responses at two weeks post-challenge was observed in vaccinated monkeys compared to control monkeys. Although all vaccinated monkeys were infected, vaccination with rMVA-J5 appeared to partially control viral replication during the acute and late phase of infection as judged by cell- and plasma-associated viral load.
Journal of Medical Primatology 09/2001; 30(4):197-206. · 1.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Tat protein of human immunodeficiency virus (HIV) is produced very early after infection, plays a key role in the virus life cycle and in acquired immunodeficiency syndrome (AIDS) pathogenesis, is immunogenic and well conserved among all virus clades. Notably, a Tat-specific immune response correlates with non-progression to AIDS. Here, we show that a vaccine based on the Tat protein of HIV blocks primary infection with the simian/human immunodeficiency virus (SHIV)89.6P and prevents the CD4 T cell decline and disease onset in cynomolgus monkeys. No signs of virus replication were found in five out of seven vaccinated macaques for almost 1 year of follow-up. Since the inoculated virus (derived from rhesus or from cynomolgus macaques) is shown to be highly pathogenic in cynomolgus macaques, the results indicate efficacy of Tat vaccination in protection against highly pathogenic virus challenge. Finally, the studies of the Tat-specific immunological responses indicate a correlation of protection with a cytotoxic T cell response. Thus, a Tat-based vaccine is a promising candidate for preventive and therapeutic vaccination in humans.
Journal of Medical Primatology 09/2000; 29(3-4):193-208. · 1.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Vaccine strategies aimed at blocking virus entry have so far failed to induce protection against heterologous viruses. Thus, the control of viral infection and the block of disease onset may represent a more achievable goal of human immunodeficiency virus (HIV) vaccine strategies. Here we show that vaccination of cynomolgus monkeys with a biologically active HIV-1 Tat protein is safe, elicits a broad (humoral and cellular) specific immune response and reduces infection with the highly pathogenic simian-human immunodeficiency virus (SHIV)-89.6P to undetectable levels, preventing the CD4+ T-cell decrease. These results may provide new opportunities for the development of a vaccine against AIDS.
Nature Medicine 07/1999; 5(6):643-50. · 22.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Studies of nonhuman primate personality have suggested that physiological correlates of relevant behavioral dimensions exist. The present study examined personality using techniques similar to those employed in human personality research. Adult male rhesus monkeys were each rated on 25 adjectives while living in their natal groups. Approximately 1.5 years later, 18 animals were inoculated with the simian immunodeficiency virus (SIV) and exposed to socially stable or socially unstable conditions. Behavior, viral load (SIV RNA), plasma cortisol concentrations, and the IgG response to SIV and to rhesus cytomegalovirus were measured at regular intervals. Multiple regression analyses revealed that the four personality dimensions (Sociability, Confidence, Equability, Excitability) were correlated with various measures. Following inoculation with SIV, animals higher in Sociability showed a more rapid decline in plasma cortisol concentrations, elevations in the anti-RhCMV IgG response, and a decline in SIV RNA. The results indicate that personality factors in rhesus monkeys do have physiological correlates that have significance for disease processes and that in the context of a social manipulation, Sociability, reflecting the tendency to engage in affiliative interactions, is an important factor in explaining outcome measures at early time points.
Brain Behavior and Immunity 07/1999; 13(2):138-54. · 5.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: The infection of cynomolgus monkeys with an attenuated simian immunodeficiency virus (SIV) (C8) carrying a deletion in the nef gene results in a persistent infection associated with an extremely low viral burden in peripheral blood mononuclear cells. The aim of this study was to determine (1) the breadth of the protection after repeated challenges of monkeys with SIV homologous strains of different pathogenicity, (2) the genotypic stability of the live virus vaccine, (3) whether the protection might depend on cellular resistance to superinfection, and (4) whether immunogenic stimuli such as recall antigens could reactivate the replication of the C8 virus. To address these goals, the monkeys were challenged at 40 weeks after C8 infection with 50 MID50 of cloned SIVmac251, BK28 grown on macaque cells. They were protected as indicated by several criteria, including virus isolation, anamnestic serological responses, and viral diagnostic PCR. At 92 weeks after the first challenge, unfractionated peripheral blood mononuclear cells from protected monkeys were susceptible to the in vitro infection with SIVmac32H, spl. At 143 weeks after C8 infection, the four protected monkeys were rechallenged with 50 MID50 of the pathogenic SIVmac32H, spl grown on macaque cells. Once again, they were protected. The C8 virus remained genotypically stable, and depletion of CD4(+) cells was not observed during approximately 3 years of follow-up. In contrast, it was found that the infection with SIVmac32H, spl induced CD4(+) cell depletion in three of three control monkeys. Of importance, stimulation with tetanus toxoid, although capable of inducing specific humoral and T cell proliferative responses, failed to induce a detectable reactivation of C8 virus.
[show abstract][hide abstract] ABSTRACT: A longitudinal characterization of immune cell subpopulations (lymphocytes, CD4+ and CD8+ cells), of routine haematological parameters and of immunoglobulin serum levels was carried out in newborn Macaca fascicularis starting from 1 week up to 1 year of life. In neonates, the percentage of CD4+ lymphocytes is almost double, while the percentage of CD8+ cells is lower than that found in adult monkeys (> 5-years old). An inverted trend in the percentage of the two T-lymphocyte subpopulations was observed during the weeks following birth, with a progressive increase of circulating CD8+, paralleled by a decrease of CD4+ cell number. Consequently, the CD4/CD8 ratio slowly decreases, even if, at 12 months of life, it is still higher than that found in adult animals. Several differences were also noted between young and adult monkeys with regard to the total number of circulating CD4+ and CD8+ cells. Haematological parameters did not show consistent differences with respect to adult values. The plasma IgG level is high at birth, then decreases until 6 months of life, while the IgM and IgA values are very low during the first weeks of life but increase in the following period. Our data showed that variations of immunological (CD4+, CD8+ cells) patterns and of some haematological parameters in M. fascicularis are dependent on age. These variations should be therefore considered whenever young animals are used in experimental protocols.
Veterinary Immunology and Immunopathology 10/1997; 59(1-2):141-50. · 1.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: Antibody titers to rhesus cytomegalovirus (RhCMV) were prospectively analyzed over a period of 68 weeks in a longitudinal serosurvey of 17 RhCMV-seropositive rhesus macaques (Macaca mulatta) experimentally coinfected with simian immunodeficiency virus (SIV). These were compared with anti-RhCMV titers in 18 animals that were also naturally infected with RhCMV but not infected with SIV. Fluctuations in anti-RhCMV antibody titers were observed within 5 weeks of SIV inoculation, and two distinct patterns of RhCMV antibody response were observed in SIV-infected animals. Animals showing a progressive decline in anti-RhCMV immunoglobulin G (IgG) exhibited the most rapid disease progression, coincident with low anti-SIV and anti-tetanus toxoid IgG responses, high levels of p27 antigen in the plasma, and short survival. Animals exhibiting a more stable CMV-specific response after SIV inoculation had the least rapid disease course. Anti-RhCMV antibody titers in SIV-uninfected animals remained relatively stable during the period of study. Evidence that preinoculation immunologic measures predicted postinoculation outcome was equivocal.
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 06/1997; 15(1):5-15.
[show abstract][hide abstract] ABSTRACT: The effect of in utero TBTO exposure on blood composition in neonates, pups during weaning, and dams in the same period were investigated in mice. The dams were gavaged at dose levels 0, 5, 10, and 20 mg TBTO/kg body weight on gestational days 6-15. At birth, litters were culled to eight pups, and blood analysis was performed on excess pups. On d 7, 14, and 21 the entire litters were sacrificed and blood (WBC, RBC, HGB, HCT, MCV, MCH, MCHC, and differential leukocyte count) of dams and pups was analyzed. Blood analysis of neonates revealed enhanced WBC count and altered red-cell parameters. Increase in WBC persisted until postnatal day (pnd) 21, while red-cell parameters regained normal values on pnd 7. No significant differences were found in thymus and spleen weights in the treated groups. Dams presented no alteration in blood composition or of spleen or thymus weights. The results of this investigation revealed that in utero exposure to TBTO induces a nonspecific alteration of hematological parameters in mice, but further studies are necessary to understand whether our results are either dependent on maternal status or a direct effect of TBTO on embryonic tissue.
Journal of Toxicology and Environmental Health 12/1995; 46(3):369-77. · 1.81 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pregnant Swiss mice were treated with 0, 5, 10, 20, and 30 mg/kg body weight of bis(tri-n-butyltin) oxide (TBTO) on d 6-15 of gestation. At birth litters were normalized to eight pups, and postnatal evaluation of pup growth rate and behavioral observations of dams were carried out. Litters were sacrificed on postnatal days (pnd) 7, 14, and 21, to perform hematological analysis, in connection with another study. Dam weight gain was impaired in all the treated groups (except at the lowest dose level) in the late phase of gestation. A high incidence of anticipated or delayed parturitions, without any correlation with fetal mass, was observed in the treated groups. All the treated dams showed a significant increase in resorptions, and a decrease in body weight gain between gestational day (gd) 6 and pnd 1. At birth, only the 20 and 30 mg/kg dose groups showed reduced litter size and reduced pup weight. Body weight gain reduction of pups persisted in wk 1 of life only in the 10 and 20 mg/kg dose groups. In addition, the maternal weight trend was affected during the lactation period in the higher dose groups. Postnatal death rate and growth rate of treated pups were affected by an altered maternal behavior; pups, apparently viable and with normal weight, were found often scattered throughout the cage with signs of wounds, and the percentage of dams that had not built a nest increased in the 10, 20, and 30 mg/kg dose groups. Total absence of parental care was noted in many litters, and many infanticidal events were reported. Our results seem to confirm low TBTO embryofetotoxicity, and strongly support the assumption that TBTO's toxicity to the mother is much stronger than its embryo-fetotoxic potential. Most of the reproductive parameters examined in this study were unaffected in the low-dose group, while some indices, such as gestation length and maternal weight gain between gd 6 and pnd 1, were markedly altered also at the 5 mg/kg dose level and appear to be sensitive parameters in assessing maternal toxicity.
Journal of Toxicology and Environmental Health 12/1995; 46(3):355-67. · 1.81 Impact Factor
[show abstract][hide abstract] ABSTRACT: A preliminary study was conducted on adult male crab-eating monkeys (Macaca fascicularis) orally exposed to bis(tri-n-butyltin)oxide (TBTO) at doses of 0 and 160 micrograms/kg/day, 6 days/wk, for 22 wk. No treatment-related signs of toxicity or changes in body weight gain were detected during the course of the study. The haematological analyses performed every 2 wk indicated a decrease in total leucocyte count in the treated animals with significant values in wk 8, 10 and 22 of treatment. No differences from controls were noted in clinical chemistry and total tin concentration in blood. These preliminary data on the toxicity of TBTO in the primate model are intended to be an initial contribution towards a better evaluation of the potential toxicological hazard of TBTO to humans.
Food and Chemical Toxicology 09/1992; 30(8):715-8. · 3.01 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pregnant mice were treated on days 6-15 of gestation with 5, 20 and 40 mg/kg/d bis(tri-n-butyltin)oxide (TBTO), and sacrificed on gestational day 17. At the highest dose TBTO caused a significant reduction of maternal body weight gain and also proved to be highly embryotoxic. Necropsy showed a dose-related decrease in spleen weight while a dose-dependent increase in placental weight was observed.
[show abstract][hide abstract] ABSTRACT: In cynomolgus monkeys, we compared two human-derived SIVmac251 whole virus vaccines, a long vs short immunization schedule, and two different challenge viruses. Both vaccines induced protection after challenge with human-derived SIVmac251/32H. There was no difference between the two schedules of immunization. Seven monkeys, five of which were protected following the first challenge, were reboosted and rechallenged with monkey-derived SIVmac251, but no protection was observed. The titers of anti-human cell or -SIV neutralizing antibodies were not related to protection.
Journal of Medical Primatology 22(2-3):110-8. · 1.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Five pregnant (two to three and one-half months) Macaca fascicularis seroconverted following immunization with sucrose-gradient purified and formalin-inactivated whole simian immunodeficiency virus (SIVmac251). No untoward effects on fetal maturation were observed during the immunization of the mothers. Antibodies to SIVmac251 (also those with in vitro neutralizing activity) were passively transferred to the offspring but disappeared within two to six months after birth. Antibodies to env glycoprotein (gp130) lasted longer than those against viral gag proteins (p26,p60).
Journal of Medical Primatology 21(2-3):91-8. · 1.11 Impact Factor