Cervical Human Papillomavirus genotypes in HIV-infected women: a cross-sectional analysis of the VALHIDATE study.

INTRODUCTION: Primary-prevention by prophylactic vaccination against HPV-related cancers and HPV-based screening programs are based on HPV-type distribution in immunocompetent individuals. HIV-infected women are at high risk of invasive HPV-disease sustained by a broader range of HPV-types and have higher multi-type infection rates than immunocompetent hosts. METHODS: This is a cross-sectional analysis of High Risk HPV (HR HPV) type distribution in 805 HIV+ women (HIW) compared with a control group of 1402 immunocompetent HIV- women (SPW) enrolled in the VALHIDATE study in order to define HPV type-specific distribution according to cytology. RESULTS: HIW had a 3.8, 3.6, and 2.7 times higher risk of atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL) than SPW respectively. HPV-DNA prevalence was 28.4% in HIW and 11.81% in SPW (p<0.0001). The prevalence of infection increased from normal cytology to HSIL both in HIW (from 21.45% to 90.91%) and SPW (from 9.54% to 75%). The OR for women with normal cytology of having a positive HPV-DNA test result of was 2.6 times higher in HIW than in SPW. The cumulative prevalence of HPV-16/18 in HSIL is much lower in HIW (36.4±28.4) than SPW (62.5±33.5). CONCLUSIONS: A higher prevalence of infection and broader HPV type distribution were observed in HIV+ women compared to the general population. More than 60% of HSIL lesions of HIW patients are caused by single or multi-type infections from non-HPV16/18 HPVs. The potential 9v-HPV vaccine coverage could be even higher than that expected for the general population given the wide panel of HPV-types observed in the HSIL of HIV+ women.

Evaluation of the abbott LCx HIV-1 RNA quantitative, a new assay for quantitative determination of human immunodeficiency virus type 1 RNA.

A new quantitative reverse transcription (RT)-PCR assay for human immunodeficiency virus type 1 (HIV-1) RNA (Abbott LCx HIV RNA Quantitative assay) has been compared with the Organon NucliSens assay on 521 retrospective samples obtained from HIV-1-positive patients monitored during highly active antiretroviral therapy, 79 of whom were assayed also by the Chiron Quantiplex 3.0 system and on characterized panels. The LCx system showed a moderate correlation (r = 0.795) and gave higher results than the NucliSens system on 245 of 327 concordant positive samples, with similar sensitivity. Correlation with Quantiplex system results was higher (r = 0.943). LCx reproducibility was very good; the procedure was simple, well controlled, and rapid (up to 48 results in 7 h). The HIV RNA quantitative assay on the LCx system is suitable for routine use.

Viral load, viral phenotype modification, zidovudine susceptibility and reverse transcriptase mutations during the first 6 months of zidovudine monotherapy in HIV-1-infected people.

We studied 14 zidovudine-naive, HIV-1-infected patients attending an infectious diseases clinic in Milan during zidovudine therapy for 6 months. We monitored CD4 cell counts, immune complex-dissociated p24 antigen, viral phenotype and viral load in plasma. The virus infecting a subset of patients was examined for zidovudine susceptibility and zidovudine resistance-associated mutations. A significant correlation was established between the increase in the CD4 cell count and the decrease in viral load (Spearman's coefficients < -0.5). Patients who were p24 antigen positive had a higher viral load (P < 0.005 at baseline and after 6 months of therapy). Patients with non-syncytium-inducing (NSI) virus had higher CD4 cell counts over time than those with syncytium-inducing (SI) virus. We also examined the viral load in relation to viral phenotype. The median viral load in patients with NSI virus was higher than in SI controls at baseline, but not after 3 and 6 months of therapy. Sequential isolates of HIV-1 were obtained from nine patients and tested for resistance to zidovudine by monitoring the drug susceptibility and the reverse transcriptase-encoding sequence. Amino acid changes at codons 70 and 215 were present in some but not all isolates with zidovudine-resistant phenotype in vitro. It was possible to perform a correlation between zidovudine susceptibility and zidovudine-associated pol gene mutations only at the 6-month time point (Spearman's coefficient = 0.076). SI phenotype was associated with the development of a decreased zidovudine susceptibility. A correlation between zidovudine-associated pol gene mutations and SI phenotype was detected at the 6-month time point.

Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system.

Epstein-Barr virus (EBV) is constantly associated with AIDS-related primary lymphomas of the central nervous system (CNS). To assess whether EBV DNA in cerebrospinal fluid (CSF) could be used as a tumour marker, CSF samples that had been taken within 180 days before death from 85 patients with HIV infection and neurological disorders at necropsy were examined retrospectively by nested polymerase chain reaction (PCR) for EBV. Histologically evident primary CNS lymphomas were found in 17 patients, and EBV was shown in tissue by in-situ hybridisation in 16 of the 16 cases examined. All 17 patients with primary CNS lymphoma had EBV DNA in CSF. EBV DNA was found in CSF from 1 of 68 HIV-infected patients without histologically detectable lymphoma at necropsy. PCR for EBV DNA in CSF was 100% sensitive and 98.5% specific for AIDS-associated primary CNS lymphoma, and may be useful as a diagnostic tumour marker.

Cytomegalovirus infection of the central nervous system in patients with AIDS: diagnosis by DNA amplification from cerebrospinal fluid.

A nested polymerase chain reaction (PCR) was evaluated for the detection of cytomegalovirus (CMV) DNA in cerebrospinal fluid (CSF). CSF and serum samples from 19 AIDS patients with intracerebral CMV infection diagnosed at autopsy were retrospectively examined. As controls, CSF and serum samples from 15 AIDS patients with only extracerebral CMV involvement at autopsy, from 10 AIDS patients without CMV infection at autopsy, and from 10 anti-human immunodeficiency virus-negative patients without ongoing CMV infection, were studied. CMV DNA was detected from patients with intracerebral CMV infection in 9 of 9, 5 of 6, and 1 of 4 CSF samples collected, respectively, 1-30, 30-90, and 90-300 days before death. Twelve of 13 sera from these patients were CMV PCR-positive. None of the control patients had CMV DNA in CSF. PCR was positive in 6 of 8 sera from AIDS patients with only extracerebral CMV infection and in serum from 1 AIDS patient without CMV involvement at autopsy. CMV PCR on CSF is highly sensitive and specific. It should be considered a rapid and reliable diagnostic method for CMV infection of the central nervous system.

HIV 1 and HIV 2 prevalence of seropositivity in a population of West Africa.

In the month of August 1986, tests for anti-HIV 1 and anti-HIV 2 antibodies were performed in people coming to the hospital of Tanguietà (North Benin) (401 subjects) and in people working in the same hospital (23 subjects). The study revealed an anti-HIV 1 antibody prevalence of 0.4% (2/424) and an anti-HIV 2 prevalence of 0.2% (1/419). Seropositivity for both antibodies (anti-HIV 1 and anti-HIV 2) was found in one case; the other case was positive only for anti-HIV 1. The changing composition of the population due to frequent migratory displacements lead us to expect some possible alterations of the registered data in the future.

PIP: In August 1986, researchers tested 424 and 419 blood serum samples from patients, hospital workers, and blood donors at a hospital in Tanguieta, Benin for HIV 1 and HIV 2 antibodies respectively. Not so long ago, this region was completely isolated, but improved roads now allow free movement of people into and out of the region. The main economic activities include sheep farming and agriculture. The HIV 1 enzyme immunoassay (EIA) test 1st detected 23 seropositive sample, but only 4 tested positive (.94%) on the repeat EIA test. These 4 individuals included asymptomatic men between 30-50 years old. The distances they lived from the hospital ranged from several kilometer-600 km, 3 of whom lived in Benin and the 4th in Burkina Faso. 1 man visited the capital frequently. Further, the Western Blot and a test checking for the presence of antibodies against core and envelope proteins of HIV 1 confirmed 2 samples positive (.47%). The researchers considered these 2 as true positives, but they considered the other 2 samples which only tested positive, but they considered the other 2 samples which only tested positive under the Western Blot test as negative. The HIV 2 EIA test 1st detected 57 seropositive samples, but only 29 tested positive (6.9%) on the repeat test. The age of these individuals (19 men and 10 women) ranged from 19-54 years. The Lav-Blot test clearly confirmed only 1 positive case (.24%) and 2 negative cases. The remaining samples generated antibody bands against HIV 2 core proteins only. The researchers considered these 26 samples as indeterminate. The same person that tested positive for HIV 2 also tested positive for HIV 1. This 50 year old man belonged to a primitive ethnic group that hunts monkeys. Overall prevalence for both HIV 1 and HIV 2 stood at 1%.

Band delta hepatitis virus infection in a population of West Africa

Em 424 amostras de soros examinadas, a prevalência da infecçäo pelo vírus da hepatite B foi de 89,6% com 15,6% de positividade para o HBsAg. Algumas das amostras pertenciam a uma populaçäo aferente e outras a pessoas trabalhando em hospital rural situado na Africa Ocidental (República Popular de Benin). Vinte e sete por cento dos indivíduos soro-positivos evidenciaram replicaçäo do vírus como demonstrado pela presença do HBcAg. Nos indivíduos HBcAb positivos, os anticorpos anti-delta foram positivos em uma freqüência de 19,7%. A presença de HBsAg em 15% das mulheres gestantes eleva a importância da transmissäo de HBV, da mäe para o filho, nesta regiäo. Os resultados apresentados podem ser comparados com aqueles obtidos em outra áreas da Africa, com condiçöes sócio-econômicas semelhantes

B and delta hepatitis virus infection in a population of west Africa.

Among the 424 serum samples examined, the prevalence of hepatitis virus infection turned out to be 89.6%, with 15.6% of HBsAg positivity. Some of the samples belonged to an afferent population and some other to workers of a West Africa rural hospital (Pop. Rep. of Benin). 27.3% of the positive subjects presented active replication of the virus, shown by the presence of HBcAg. Among the HBcAb positive subjects the anti-delta antibodies showed a positivity frequency of 19.7%. HBsAg presence in 15% of pregnant women suggested the importance of HBV mother-foetal transmission in the district. The examined results can be compared with those obtained in other African areas, with similar socio-economic conditions.

Early diagnosis of HIV infection in infants.

Eighteen infants born to anti-HIV-positive mothers were tested bimonthly for immunoglobulin M (IgM) anti-HIV by Western blot and HIV p24 antigen (Ag) by enzyme-linked immunosorbent assay (ELISA) in order to determine the role of these markers in the early diagnosis of HIV infection. Twelve healthy infants were also studied as a control group. In 11 out of 18 children (61.1%) an IgM response was demonstrable, in 13 out of 18 (72.2%) IgM anti-HIV and/or p24 antigen (Ag) were detected. Two patterns of IgM response were identified: a precocious IgM positivity (group of five children positive at birth) and a later appearance of IgM, always within the third month (six cases). Early p24 antigenemia occurred in one infant. Three out of four children who developed antigenemia after birth were symptomatic within the sixth month. No clinical or immunological abnormalities were found among the three children who were persistently negative for both IgM anti-HIV and p24 Ag. Serial IgM anti-HIV and p24 Ag testing may be helpful in the early identification of HIV-infected patients.

[Antibodies against the 15 amino acid sequence 599-613 of HIV-1 glycoprotein 41 in subjects at risk of HIV infection]. / Anticorpi contro la sequenza aminoacida 599-613 della glicoproteina 41 dell'HIV 1 in soggetti a rischio di infezione per il virus.

A peptide (called A-15) composed of 15 amino acids of the gp41 (from position 599 to position 613 of the sequence encoded by the env gene) of HIV-1 has been used as an antigen to search for antibodies in 347 sera of at-risk for HIV-1 infection subjects. The purpose was of comparing the prevalence of these antibodies with that of HIV-1 total EIA antibodies and HIV-1 immunoblotting antibodies. Assuming immunoblotting test as reference test for detecting a HIV-1 infection, the antibodies against peptide A-15 show the same sensitivity and specificity when compared with other HIV-1 total EIA antibodies tests.

Viral antibodies in serum and cryoprecipitate of patients with essential mixed and secondary cryoglobulinemia. Preliminary results.

Antibodies to measles virus, CMV, HSV1, HSV2 and EBV have been tested in 9 patients with essential mixed cryoglobulinemia (EMC) and 24 patients with cryoglobulinemia associated with lymphoproliferative, autoimmune or hepatic diseases (secondary cryoglobulinemia, SC). The assays were performed in serum, cryoprecipitate and supernatant by using immunoenzymatic methods. The highest prevalence was observed in the supernatant of both EMC and SC patients. Antibodies to measles virus show a serum/cryoprecipitate ratio higher than that of the other viral agents. Statistically significant differences between EMC and SC patients in the positivity of the various viral antibodies were not shown.

[Delta co-infection: prevalence, severity and association with risk factors]. / La coinfezione delta: prevalenza, gravità e associazione con fattori di rischio.

The prevalence of delta coinfection in course of acute B hepatitis has been studied in two periods (September-November 1984: 51 cases; April-June 1985: 50 cases). The prevalence resulted of 37.2% in the first period and of 48% in the second, without a statistically significant increase. Delta coinfection did not show greater severity, as evaluated by the levels of AST, ALT, total bilirubin and prothrombin activity, than hepatitis B not coinfected. The only factor of risk statistically significant for the acquisition of delta coinfection was i.v. drug abuse.

Prevalence of HTLV III/LAV and other viral antibodies in normal and at risk populations.

The prevalence of HTLV III/LAV antibody has been studied in six groups of population: healthy subjects, a virological laboratory staff, prisoners, drug addicts, patients with lymphoadenopathy-associated syndrome (LAS) and patients with AIDS. Prevalences and levels in the same groups of HBsAg and CMV, HSV 1 and HSV 2 antibodies have been studied, too. As expected, the prevalence of HTLV III/LAV antibody increases in the six groups with the increasing of the risk while the prevalences of the other markers of viral infection do not show such a pattern. The levels of positivity of CMV antibody are significantly higher in the prisoners and LAS groups versus healthy subjects suggesting a possible role of this virus in the developing of full-blown AIDS.

[The role of delta agent in particularly severe acute hepatitis B and non-A, non-B hepatitis in HBsAg carriers]. / Il ruolo dell'agente delta in corso di epatite B acuta di particolare gravità e di epatite nAnB in portatori di HBsAg.

Role of delta agent in course of acute hepatitis B of particular severity and of hepatitis nAnB in carriers of HBsAg. Eighty-four cases of acute viral hepatitis have been studied with regard to the positiveness for delta antigen and anti-delta antibody in the Laboratory of clinical-chemical and microbiological analyses of the Hospital "L. Sacco" of Milan. The cases have been grouped in two classes: acute B hepatitis with prothrombin time of less than 40% acute viral hepatitis nAnB in chronic carriers of HBsAg. The prevalence of delta hepatitis was of 47.1% in the first class, while it was of 22% in the second class.

[An influenza outbreak of type A and type B influenza viruses]. / Osservazioni su di un episodio epidemico da virus influenzali di tipo A e di tipo B.

Results of investigations carried out during an outbreak of influenza occurred in January 1981 in a School of Milan are reported and discussed. A total of 9 type A (H1N1) influenza virus strains, antigenically intermediate between A/USSR/90/77 and A/Brazil/11/78 variants, and 2 type B influenza virus strains, antigenically intermediate between B/Hong Kong/8/73 and B/Singapore/222/79 variants, have been isolated. In one case both epidemic strains have been simultaneously detected. From the results of type-specific complement-fixing antibody titration it appears that an influenza virus infection occurred in 64% of the 300 subjects serologically examined. In 43% of the cases type A strain was involved, in 12% type B strain and in 9% both serotypes. Judging from the data of school absenteeism it seems that infections by type A virus were more severe than those by type B virus. Finally, because a group of pupils attending the school had been vaccinated in December 1978, it has been demonstrated that the rate of type A presumptive infections was correlated to the hemagglutination-inhibiting antibody titers attained after vaccination.