Persistent hepatitis C virus RNA replication in haemophiliacs: role of co-infection with human immunodeficiency virus

In order to evaluate the evolution of transfusional hepatitis C in haemophiliacs, we performed a retrospective study of ALT levels and HCV viraemia with a RNA PCR assay in 57 patients. We found that the vast majority of HCV-infected patients remained viraemic (43/57 = 75%) and higher ALT levels correlated with HCV viraemia. Although indicators of the transfusional viral load (age, severity of haemophilia) and HBV co-infection did not correlate with HCV RNA replication, HIV seropositivity was strongly associated with persistence of HCV viraemia (23/25 = 92% in HIV-positive versus 20/32 = 62% in HIV-negative patients), without any correlation with CD4 counts. Genotyping of HCV in the 43 viraemic patients shows more frequent genotype 1 in the HIV-seropositive group (14/23) than in the seronegative group (6/20). Our data emphasize that besides the role of the immunodeficiency status, the genotypes of HCV might be involved in the differences observed in terms of HCV RNA replication between the HIV-seropositive and seronegative haemophiliacs.     

The treatment of chronic hepatitis C with interferon in patients infected with the human immunodeficiency virus. The Spanish Group for the Study of Viral Hepatitis in HIV+ Patients

BACKGROUND: Alfa-interferon (aIFN) is widely recommended for the treatment of chronic hepatitis C (CHC). Hepatitis C virus (HCV) infection is very common in injecting drug users (IDUs), which in Spain represent the large number of HIV-infected persons. Interaction between human immunodeficiency virus (HIV) and HCV in coinfected patients might accelerate the clinical course of HCV-associated liver disease. The efficacy and safety of aIFN therapy in HIV-infected patients with CHC is not well known. PATIENTS AND METHODS: In a multicenter, prospective, open, non randomized and partially controlled study, we compared the efficacy and safety of aIFN therapy in 119 patients with CHC, of whom 90 were HIV-positive and 29 HIV-negative. Interferon was started at 5 mega U tiw for 3 months, followed in responders by 3 megaU tiw for additional 9 months. RESULTS: One hundred seven patients completed the study. A normalization of the aminotransferase values at the end of treatment (complete response, CR) was observed in 26/80 (32.5%) HIV-positive and 10/27 (37.0%) HIV-negative individuals (p = 0.666). Relapses at 12 months of stopping aIFN were seen in 30.8% of HIV-positive subjects and 12.5% of HIV-negatives (p = 0.403). Side effects were uncommon and did not have severity; only one patient required to stop the medication. However, 3 HIV-positive subjects treated with aIFN (3.5% of them) showed an irreversible fall of CD4+ T-cells below half the baseline values. CONCLUSION: HIV-infected patients with CHC seems to respond to aIFN with a similar rate than HIV-negatives. Moreover, the drug is similarly well tolerated in both groups of patients, although a fall of CD4+ T-cells is an unusual side effect of particular relevance observed in HIV-infected patients.     

Determination of 7alpha-hydroxycholesterol in dog plasma by high-performance liquid chromatography with fluorescence detection

One of the groups at highest risk of anal cancer is homosexual and bisexual men. Like cervical cancer, anal cancer is associated with human papillomavirus (HPV) infection. Anal HPV infection was characterized in a study of 346 human immunodeficiency virus (HIV)-positive and 262 HIV-negative homosexual and bisexual men. Anal HPV DNA was detected in 93% of HIV-positive and 61% of HIV-negative men by polymerase chain reaction. The spectrum of HPV types was similar in HIV-positive and HIV-negative men, with HPV-16 the most common type. Infection with multiple HPV types was found in 73% of HIV-positive and 23% of HIV-negative men. Among HIV-positive men who were positive by hybrid capture for group B HPV types (16/18/31/33/35/39/45/51/52/56/58) or group A types (6/11/42/43/44), lower CD4 cell levels were associated with higher levels of group B DNA (P = .004) but not group A DNA. These data suggest increased replication of the more oncogenic HPV types with more advanced immunosuppression.     

Human T cell lymphotropic virus type I does not increase human immunodeficiency virus viral load in vivo

Human T lymphotropic virus type I (HTLV-I) can increase human immunodeficiency virus (HIV) replication in vitro, and several studies suggest that HTLV-I accelerates the progression of HIV infection. To determine whether HTLV-I enhances HIV replication in vivo, a case-control study was done of serum HIV viral load, using polymerase chain reaction, in 23 subjects with HTLV-I/HIV coinfection and 92 control subjects with HIV single infection. The geometric mean serum RNA level was 11,482 copies/mL in the coinfected group and 13,804 in the single-infection group (P = .57), a result that did not change after adjustment for zidovudine use and CD4 cell count. Among subjects with advanced HIV infection, there was a trend toward higher viral load among singly infected subjects. HTLV-I did not appear to increase HIV plasma RNA levels in subjects with coinfection. These results do not provide a biologic basis for the hypothesis that HTLV-I accelerates the course of HIV infection.     

Quantitation of hepatitis G and C viruses in the liver: evidence that hepatitis G virus is not hepatotropic

Hepatitis G virus (HGV) is prevalent in patients with chronic liver disease and has been previously detected in liver specimens. However, it is unknown whether the virus is replicating in the liver or is simply a contaminant from serum. We sought to determine whether HGV was hepatotropic and to determine whether coinfection with HGV and hepatitis C virus (HCV) influenced the level of either virus. Virus was quantitated using branched DNA (bDNA) assay for both HGV and HCV in the liver explants and pretransplant serum samples from 30 transplant recipients: Group I, HGV/HCV coinfection (n = 10); group II, HCV infection alone, (n = 8); group III, HGV alone (n = 12). In patients with coinfection HCV (RNA) titers in liver were consistently higher than those for HGV RNA (median 1.13 x 10(8) and 360,000 Eq/g respectively, P < .01). The ratio of liver/serum viral RNA was significantly higher for HCV than for HGV (median 129 and 0.3 respectively, P < .01). Levels of HCV RNA were similar in patients with HCV infection alone versus those with HGV/HCV coinfection (median; liver = 1.15 x 10(7) vs. 1.13 x 10(8) Eq/g, serum = 500,000 vs. 200,000 Eq/mL) and levels of HGV RNA in liver and serum were similar in patients with HGV infection alone compared to those with HGV/HCV coinfection (median; liver = 1.2 x 10(6) vs. 4.0 x 10(5) Eq/g, serum = 4.5 x 106 vs. 2.6 x 10(6) Eq/mL). Levels of either virus appeared unaffected by the presence of an additional virus. The high ratio of HCV RNA levels in liver compared to serum is consistent with its known hepatotropism, but this pattern was not observed for HGV. The median liver/serum ratio of HGV RNA was less than unity, a finding consistent with serum contamination of liver tissue. Thus we conclude that the liver is not the main site of HGV replication.     

Endogenous interleukin-2 serum levels in children infected with human immunodeficiency virus

Levels of interleukin-2 (IL-2) in serum obtained from human immunodeficiency virus (HIV)-infected children at health maintenance visits were measured to characterize endogenous IL-2 responses and to examine the association between these responses and progression of immunosuppression. IL-2 was detectable (level >8.7 pg/mL) in the serum of 28 of 45 HIV-infected children; 42% (19 of 45) had serum IL-2 levels of >39 pg/mL. Children without evidence of immunosuppression (Centers for Disease Control and Prevention Pediatric HIV Classification Immunologic Category 1, n = 15) and children with severe immunosuppression (immunologic category 3, n = 20) had statistically significant lower serum IL-2 levels (mean +/- [SD], 134.4 +/- 227.3 pg/mL and 18.2 +/- 30.3 pg/mL, respectively) than those with moderate immunosuppression (mean +/- [SD], 450.5 +/- 311.8 pg/ml; immunologic category 2, n = 10) (P < .05, Wilcoxon rank sum test). In those children in whom immunosuppression was evident, decreasing serum IL-2 levels correlated with depletion of CD4+ lymphocytes (r = 0.74), whereas there was an inverse correlation between serum IL-2 levels and CD4+ lymphocyte counts (r = -0.47) in children with no or moderate immunosuppression.     

Effect of immunosuppression on composition of quasispecies population of hepatitis C virus in patients with chronic hepatitis C coinfected with human immunodeficiency virus

BACKGROUND/AIMS: To study the effects of the immunosuppression caused by the reduction of CD4 activity on the composition of hepatitis C virus (HCV) populations, we analyzed the number of HCV quasispecies clones and the nucleotide diversity of the hypervariable region 1 (HVR1) of HCV in 37 patients with hemophilia with persistent HCV infection, with or without human immunodeficiency virus (HIV). METHODS: The numbers of HCV quasispecies clones were measured by fluorescence single-strand conformation polymorphism analysis. Direct sequencing was used to analyze the degree of diversity of HVR1. We compared these values according to coinfection with HIV, and CD4 counts of patients. RESULTS: There were no differences in either the number of HCV clones or the diversity between patients with and without HIV coinfection. In HIV coinfected patients the diversity decreased in association with the decrease in CD4 count while the number of HCV clones did not. The diversity of HVR1 was 3.64 +/- 5.03% in patients with a CD4 count < 50/microliters and 14.92 +/- 6.03% in patients with a CD4 count > or = 50/microliters; it was significantly lower in the former (p = 0.0002). CONCLUSIONS: A severe reduction in the CD4 count, which is considered to cause a decline in the activity of helper T-lymphocytes, induced changes in the composition of HCV populations; one or a few quasispecies clones are predominant in the HCV population in the serum of individual patients.     

Frequency of symptomatic and asymptomatic herpes simplex virus type 2 reactivations among human immunodeficiency virus-infected men

Herpes simplex virus (HSV) infection is common in persons coinfected with human immunodeficiency virus (HIV). In a prospective study, daily viral cultures of the mouth, genitals, and rectum were collected from 68 HIV-positive and 13 HIV-negative men who have sex with men. Subjects completed a median of 57 days of follow-up. Anogenital HSV-2 cultures were positive on 405 (9.7%) of 4167 days for HIV-positive men and on 24 (3.1%) of 766 days for HIV-negative men. Most reactivations were perirectal and subclinical. Risk factors for increased HSV-2 shedding among HIV-positive men were low CD4 cell count (odds ratio, 2.5; 95% confidence interval, 1.2-5.4) and antibodies to both HSV-1 and HSV-2 versus HSV-2 only (odds ratio, 1.9; 95% confidence interval, 1.0-3.7). Three isolates obtained from 3 separate subjects were resistant to acyclovir. Thus, subclinical HSV-2 reactivation is an important opportunistic infection in persons with HIV infection. Further studies are necessaryto determine the impact of subclinical HSV-2 reactivation on the natural history of HIV infection.     

Adenovirus infections in human immunodeficiency virus-positive patients: clinical features and molecular epidemiology

Prospective surveillance of 63 human immunodeficiency virus (HIV)-positive patients and 9 HIV-negative partners over 5-27 months yielded 51 adenoviruses from 18 HIV-positive patients. These were serotyped and compared by restriction enzyme analysis (REA) together with 24 isolates from 19 other HIV-positive patients. The actuarial risk of infection at 1 year in HIV-positive patients was 28% (17% with entry CD4 cell count of > 200/mm3 and 38% with CD4 cell count of < or = 200/mm3, P = .03). The most frequent site of infection was gastrointestinal (17/18 patients) with mainly subgenus D adenoviruses, while urinary infection was caused by subgenus B or D. Prolonged fecal excretion (2-27 months) was associated with CD4 cell counts < 150/mm3. Identical strains were seen in 2 HIV-positive partners and 2 unrelated patients. Gastrointestinal infection was temporally associated with diarrhea in only 7 (41%) of 17 cases. The remainder (59%) were asymptomatic or minimally symptomatic, and diarrhea was often caused by other opportunistic pathogens.     

Hepatitis C virus genotype in anti-HCV-positive hemodialysed patients

We investigated the influence of hepatitis C virus (HCV) genotypes on the clinical course of HCV infection in a haemodialysis population. In June 1991, a 4 year prospective follow-up programme was implemented in 184 consecutive haemodialysis patients. Alanine aminotransferase (ALT) and gamma glutamine transferase (GGT) were performed every 2 months. When HCV antibody (Ab) (by second-generation ELISA) was positive, it was confirmed by RIBA 2 and HCV RNA amplification by PCR. The pattern of nucleotide sequence variability in the 5' non-coding region was categorized according to Simmonds' genotype classification. Risk factors including blood transfusions were evaluated. The levels of hepatic enzymes in HCV Ab-positive patients were retrospectively studied over a mean period of 11.8 years. ALT and GGT levels were assigned a score for every year of infection (0 = normal, 1 = fluctuating 2 = high levels). Fifty-two patients were HCV Ab reactive (30.4%), eight were RIBA undetermined and 44 were RIBA positive; 40 of these were HCV RNA positive (91%). Twelve patients were HCV RNA negative, suggesting that they had recovered from the infection. Four genotypes were identified: 1b [26 patients (65%)], 1a (one patient), 2 [12 patients (30%)] and 3 (one patient). The genotype distribution was not different from that found in patients with chronic hepatitis C and normal renal function of the same geographical area. Genotype 1b accounted for 75% of the cases before 1985 and an equal prevalence of the two major genotypes was observed after 1985. Patients infected with HCV subtype 1 had normal mean ALT levels, but higher levels in the follow-up period (28 +/- 15.6 IU/l) and higher ALT and GGT personal scores in the retrospective study. Genotype 1 patients had higher mean ALT levels after 6 months. HCV RNA-negative patients had lower ALT levels after 24 months. RIBA pattern could differentiate the patients. Patients with genotype 1 received a higher number of transfusions, while only 50% of HCV RNA-negative patients had been transfused. Our data suggest a worse course of HCV infection in haemodialysis patients infected with HCV subtype 1, but the severity of HCV infection can only be assessed by histology. Transaminases are only loosely correlated with severity.     

Kidney morphological changes in relation to long-term renal function and metabolic control in adolescents with IDDM

OBJECTIVE: To investigate the impact of HIV infection on the prevalence, incidence and short-term prognosis of squamous intraepithelial lesions (SIL), in a prospective study with 1-year follow-up. METHODS: Between 1993 and 1995, 271 HIV-positive and 171 HIV-negative women at high risk of HIV infection were recruited, 365 (82.6%) of whom completed the 1-year follow-up. The women underwent a Papanicolaou smear test at inclusion and at 6 and 12 months. Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. RESULTS: The SIL prevalence ranged from 7.5% for HIV-negative to 31.3% for HIV-positive women with CD4 cell counts < 500 x 10(6)/l (P < 0.001). Other factors associated independently and significantly with SIL prevalence were HPV-16, 18, 33 and related types, HPV-31, -35, -39 and related types, lifetime number of partners, younger age, past history of SIL and lack of past cervical screening. The SIL incidence ranged from 4.9% in HIV-negative women to 27% in HIV-positive women with CD4 cells < 500 x 10(6)/l (P < 0.001). Progression from low- to high-grade SIL during follow-up was detected in 38.1% of HIV-positive women with CD4 cells < or = 500 x 10(6)/l but in no HIV-negative nor HIV-positive women with CD4 cells > 500 x 10(6)/l. HPV-16, 18, 33 and related types were also associated with higher incidence of SIL and progression from low- to high-grade SIL. CONCLUSION: HIV-induced immunodeficiency is associated with high prevalence, incidence and persistence/progression of SIL. A pejorative influence of HIV infection without marked immunodeficiency is less clear. HIV-positive women with SIL may thus benefit from early treatment when a useful immune response is still present.     

HIV infection affects parietal-dependent spatial cognition: Evidence from mental rotation and hierarchical pattern perception.

Human immunodeficiency virus (HIV) in the asymptomatic phase of the infection impairs some aspects of cognition, but little is known about how visuospatial functions are affected. In the present study, performance on tasks of mental rotation and hierarchical pattern perception was investigated in 14 HIV-positive men and 12 age- and education-matched HIV-negative men. Processes related to mental rotation of objects and hands were impaired in HIV-positive participants as compared to the HIV-negative group. The HIV-positive group was also impaired on hierarchical pattern perception of local targets under global biasing conditions. Consistent with these results, the HIV-positive participants showed impaired performance on standard clinical neuropsychological tests of visuospatial function. These findings indicate that the detrimental effects of HIV on cognition appear even in asymptomatic individuals and affect diverse visuospatial functions that depend upon the integrity of parietal brain regions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human immunodeficiency virus replication in AIDS patients with Mycobacterium avium complex bacteremia: a case control study. California Collaborative Treatment Group

The development of opportunistic infections and the administration of vaccines have been associated with transient increases of human immunodeficiency virus (HIV) RNA plasma levels in HIV-infected patients. To determine the relationship between Mycobacterium avium complex (MAC) bacteremia and HIV RNA levels, HIV RNA levels in patients who developed MAC bacteremia (cases) were compared with levels in patients who remained free of MAC disease (controls). Cases and controls were matched for CD4 cell count, prophylaxis against MAC disease, antiretroviral therapy, and duration of follow-up. Mean baseline HIV RNA levels were 4.8 log10 copies/mL in cases and 4.6 log10 copies/mL in controls (P = 0.22). HIV RNA levels increased by a median of 0.4 log in cases but not controls at the time of MAC bacteremia (P = 0.01). In AIDS patients, the onset of MAC bacteremia is associated with a modest but significant increase in serum HIV RNA levels. Increased HIV replication may contribute to the higher mortality associated with MAC bacteremia.     

Association between human immunodeficiency virus and herpes simplex virus type 2 seropositivity among male factory workers in Zimbabwe

To determine the seroprevalence of herpes simplex virus type 2 (HSV-2), to identify correlates of infection, and to describe the correlation with human immunodeficiency virus (HIV) seropositivity, 224 HIV-negative and 191 HIV-positive male factory workers in Zimbabwe were screened for HSV-2-specific antibodies. HSV-2 seroprevalence was 35.7% among HIV-negative subjects and 82.7% among HIV-positive subjects. The weighted estimate of HSV-2 seroprevalence in this population is 44.6%. The correlation between HIV and HSV-2 remained significant after controlling for multiple sex partners, paying for sex, and history of sexually transmitted disease (adjusted odds ratio, 8.0; 95% confidence interval, 4.8-13.1). If the association between HSV-2 and HIV is causal, then the high seroprevalence of HIV and HSV-2 suggests that suppressive HSV-2 treatment should be considered as a strategy to reduce HIV transmission in this population. HSV-2 seroconversion may be a suitable surrogate end point to evaluate HIV prevention interventions.     

Increased transmission of vertical hepatitis C virus (HCV) infection to human immunodeficiency virus (HIV)-infected infants of HIV- and HCV-coinfected women

The transmission of perinatal hepatitis C virus (HCV) infection was studied retrospectively in 62 infants born to 54 HCV- and human immunodeficiency virus (HIV)-coinfected women enrolled in a prospective natural history study of HIV transmission. Infant HCV infection was assessed by nested RNA polymerase chain reaction. The overall rate of vertical HCV transmission was 16.4% (9/62). Most HCV-infected children did not develop antibodies to HCV. The rate of HCV infection was higher among HIV-infected infants (40%) than among HIV-uninfected infants (7.5%; odds ratio, 8.2; P = .009). This difference in transmission was not related to differences in maternal HCV load, as measured by branched DNA assay, or mode of delivery. Why HIV-infected infants of HCV- and HIV-coinfected women have significantly higher rates of perinatal HCV transmission remains to be elucidated. The rate of HCV transmission in HIV-uninfected infants of HCV- and HIV-coinfected women is similar to that reported for infants born to HIV-seronegative mothers.     

Spectrum of disease among HIV-infected adults hospitalised in a respiratory medicine unit in Abidjan, C?te d'Ivoire

SETTING: Respiratory medicine wards of the University Teaching Hospital, Abidjan, C?te d'Ivoire. OBJECTIVES: To describe the spectrum of opportunistic infection among human immunodeficiency virus (HIV) infected adults hospitalised in the respiratory medicine unit in Abidjan, and the level of immunosuppression at which these diseases occur. DESIGN: Cross-sectional study. RESULTS: Overall, 75% of patients were HIV-positive: among these patients, the most frequent diagnosis was tuberculosis, in 61%, followed by bacterial pneumonia (15%), Gram-negative septicaemia (particularly non-typhoid Salmonella) (9%) and empyema (5%). Atypical pneumonias appeared to be rare. Most HIV-positive patients had CD4 counts indicative of advanced immunosuppression: 36% had CD4 counts below 100 x 10(6)/l, 19% between 100 and 199 x 10(6)/l, 29% between 200 and 499 x 10(6)/l, and 16% above 500 x 10(6)/l. Overall in-hospital mortality was 27% for HIV-positive patients and 22% for HIV-negative patients (P = 0.5). In a multivariate analysis, the strongest independent risk factors for death were cachexia (odds ratio [OR] 7.4, 95% confidence interval [CI] 2.1-26.3), male sex (OR 4.5, 95% CI 1.2-17.4) and age over 40 (OR 4.1, 95% CI 1.0-17.2). CONCLUSIONS: Tuberculosis and bacterial infections are the major causes of respiratory morbidity in immunosuppressed HIV-infected adults in this population. Efforts to improve the management of HIV-related disease need to focus on prevention and treatment of these infections.     

The prevalence of herpes family virus DNA in the conjunctiva of patients positive and negative for human immunodeficiency virus using the polymerase chain reaction

OBJECTIVE: To help understand the pathogenesis of herpes family virus ocular infection among patients positive for HIV, the authors compared the rates of detection of herpes family virus DNA from the conjunctiva of patients who are positive and negative for human immunodeficiency virus (HIV) using the polymerase chain reaction (PCR). DESIGN: Cross-sectional study. PARTICIPANTS: The conjunctival scrapings of 30 patients positive for HIV and 30 patients negative for HIV were examined. INTERVENTION: PCR was used to assay for the presence of herpes simplex virus type 1 (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) DNA (n = 240 samples). MAIN OUTCOME MEASURE: The rate of detection of virus DNA in the two groups, controlling for age, gender, and race, was measured. RESULTS: HSV and VZV DNA were not detected in any of the HIV-positive or HIV-negative samples. CMV DNA was detected in 20% (6 of 30) of patients positive for HIV and was undetected in control subjects negative for HIV (P = 0.01). EBV DNA was detected in 40% (12 of 30) of patients positive for HIV and in 47% (14 of 30) of control subjects negative for HIV (P = 0.58). CONCLUSIONS: There was no difference in the frequency of detection of HSV, VZV, or EBV DNA from the conjunctiva of patients positive or negative for HIV. Only CMV DNA was detected at a significantly higher rate in the conjunctiva of patients positive for HIV compared with control subjects negative for HIV. These different rates of peripheral virus shedding may be one possible explanation for the different rates of clinical infection among the herpes family viruses among patients positive for HIV.