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In a retrospective analysis of lower respiratory tract infections in an ex-injection-drug users community, we found an outbreak (April to July 1991) of Chlamydia pneumoniae infection. The epidemic occurred in [...]

Intravenous (IV) drug users are at risk of acquiring hepatitis B infection, which affects the liver. A vaccine against hepatitis B has recently been developed, and it may be the only means of protecting IV drug users. This is especially true since many IV drug users are infected with human immunodeficiency virus (HIV, the virus that causes AIDS). This can make them even more susceptible to hepatitis B, since HIV weakens the immune system. Fifty-five IV drug users enrolled in a drug detoxification program were vaccinated with the hepatitis B vaccine known as Engerix B. Forty-one healthy individuals from the community were also vaccinated and served as controls. Seventeen of the drug users had no evidence of previous hepatitis B, while 15 had evidence of a past infection, and 23 had evidence of a recent infection. Each group received three injections, one at the beginning of the study, one a month later, and one six months later. One month after the third vaccination, 76 percent of the drug users with no history of hepatitis B had responded to the vaccine (by producing antibodies), 6 percent with past infection had responded, and 69 percent with recent infection had responded. In contrast, 97 percent of the healthy individuals had responded. The drug users had lower levels of protective antibodies against hepatitis B virus. Two years after the first vaccination, only 43 percent of drug users with no history of hepatitis B infection had protective antibodies, compared with 86 percent of the controls. Among the IV drug users who had a prior infection with hepatitis B, none of those with past a infection had protective antibodies, and only 31 percent of those with a recent infection had them. Drug users who exhibited anergy (a decreased immune response to foreign substances) were less likely to respond to the vaccine. The vaccine used in this study may not be able to stimulate the immune system to produce protective antibodies as well as other forms of hepatitis B vaccine; other studies of hepatitis vaccination in IV drug users have shown response rates of 90 to 100 percent. The fact that many nonresponders were anergic indicates that their immune systems might be weakened. However, since many of the drug users responded to the vaccine, vaccination of IV drug users against hepatitis B may still be effective. (Consumer Summary produced by Reliance Medical Information, Inc.)

Influenza outbreaks can be difficult to control in confined settings where high‐risk individuals are concentrated. Following the occurrence of a large number of cases of influenza‐like illness in a rehabilitation community for drug users, between February and March 2004, surveillance activities were implemented. Attack rates of influenza‐like illness were calculated, and risk factors for the development of disease and complications were evaluated through the use of relative risks (RR) with 95% confidence intervals (CI). Nasal‐pharyngeal samples were collected for virological studies. Of 1,310 persons who were living in the community, 209 were diagnosed with influenza‐like illness: the attack rate (15.9% overall) was higher for HIV‐infected persons (RR: 1.77, 95% CI: 1.32–2.37), older individuals, and dormitory residents. HIV‐infected participants were also more likely to develop complications compared with HIV‐uninfected persons diagnosed with influenza‐like illness (RR: 5.13, 95% CI: 2.52–10.20). The outbreak was attributable to Christchurch‐like influenza A strains. Vaccination was ineffective because of the mismatch between wild and vaccine strains. J. Med. Virol. 78:1218–1222, 2006. © 2006 Wiley‐Liss, Inc.

Apoptosis is critical to the progression of human immunodeficiency virus-1 (HIV-1) infection. It appears reasonable that antiretroviral therapies may not achieve a full control of the infection in the absence of an impact on apoptosis. We assigned 20 asymptomatic HIV-infected subjects with advanced immunodeficiency to receive either zidovudine (AZT), and didanosine (DDI) or the same regimen plus L-carnitine, a known antiapoptotic drug, for 7 months. Immunologic and virologic parameters were measured at baseline and after 15, 60, 120, and 210 days of treatment. We assessed on each time point the following: (a) the frequency of peripheral blood apoptotic CD4 and CD8 lymphocytes, CD4 and CD8 cells with disrupted mitochondrial membrane potential, and CD4 and CD8 cells undergoing oxidant stress; (b) the expression of the molecular markers of apoptosis Fas and caspase-1; and (c) the expression of p35/cdk-5 regulatory subunit that is involved in regulating cell survival and apoptosis. Absolute CD4 and CD8 counts and plasma viremia were also measured. Apoptotic CD4 and CD8 cells, lymphocytes with disrupted mitochondrial membrane potential, and lymphocytes undergoing oxidant stress were greatly reduced in subjects treated with AZT and DDI plus L-carnitine compared with those who did not receive L-carnitine. Fas and caspase-1 were down-expressed and p35 over-expressed in lymphocytes from patients of the L-carnitine group. No difference was found in CD4 and CD8 counts and viremia between the groups. No toxicity of L-carnitine was recognized. The addition of L-carnitine is safe and allows apoptosis and oxidant stress to be greatly reduced in lymphocytes from subjects treated with AZT and DDI.

The immunogenicity of an anti‐influenza vaccine was assessed in 409 former intravenous drug user volunteers and its effect on the levels of HIV‐1 RNA, proviral DNA and on CD4+ lymphocyte counts in a subset HIV‐1‐positive subjects was measured. HIV‐1‐positive individuals (n = 72) were divided into three groups on the basis of their CD4+ lymphocyte counts, while the 337 HIV‐1‐negative participants were allocated into group four. Haemagglutination inhibiting (HI) responses varied from 45.8 to 70% in the HIV‐1‐positive subjects and were significantly higher in group four (80.7% responses to the H1N1 strain, 81.6% to the H3N2 strain, and 83% to the B strain). The percentage of subjects with HI protective antibody titres (≥ 1:40) increased significantly after vaccination, especially in HIV‐1 uninfected subjects. Immunization caused no significant changes in CD4+ counts and in neither plasma HIV‐1 RNA nor proviral DNA levels. Therefore, vaccination against influenza may benefit persons infected by HIV‐1. J. Med. Virol. 65:644–648, 2001. © 2001 Wiley‐Liss, Inc.

The progression of HIV-1 disease appears associated with an unregulated Fas-mediated apoptosis of lymphocytes that involves the activation of ICE protease and ceramide generation and antiviral therapy may not be fully effective in the absence of a relevant impact on apoptosis.Six drug-naive HIV-1-infected symptomless patients with advanced immunodeficiency were treated with combined AZT and dd1 for 4 months; plasma HIV-1 RNA levels, the counts of CD4 cells, CD4 and CD8 apoptotic lymphocytes, Fas-positive cells and ICE-positive cells, and intracellular ceramide levels were measured at base-line and after 7, 45 and 120 days of treatment.There was a prompt reduction in plasma viremia and a secondary increase in CD4 counts, but the treatment had no impact on apoptotic CD4 and CD8 lymphocytes, Fas-positive cells and ICE-positive cells, and on the intracellular levels of ceramide.A discrepancy exists between the positive impact of combined AZT and ddl treatment on plasma viral load and CD4 counts and the lack of any effect on the process of lymphocyte apoptosis. We suggest to use the measurement of apoptotic lymphocytes as a surrogate marker to predict, in combination with viral load and CD4 counts, a large proportion of the clinical effect of antiviral therapy.

The Fas/Fas ligand system is involved in uncontrolled apoptosis, which ultimately leads to the loss of T lymphocytes in human immunodeficiency virus (HIV)-infected individuals. The signal transduced by Fas receptor involves the activation of an acidic sphingomyelinase, sphingomyelin breakdown, and ceramide production. Our recent reports have shown that L-carnitine inhibits Fas-induced apoptosis and ceramide production both in vitro and in vivo. The aim of this study was to study, in a preliminary fashion, the impact of long-term L-carnitine administration on CD4 and CD8 absolute counts, rate, and apoptosis in HIV-1–infected subjects. The generation of cell-associated ceramide and HIV-1 viremia was also investigated. Eleven, asymptomatic, HIV-1–infected subjects, who refused any antiretroviral treatment despite experiencing a progressive decline of CD4 counts, were treated with daily infusions of L-carnitine (6 g) for 4 months. Immunologic and virologic measures and safety were monitored at the start of the treatment and then on days 15, 30, 90, and 150. L-carnitine therapy resulted in an increase of absolute CD4 counts, which was statistically significant on day 90 and 150 (P = .010 and P = .019, respectively). A positive, not significant trend was also observed even in the change in absolute counts of CD8 lymphocytes. L-carnitine therapy also led to a drop in the frequency of apoptotic CD4 and CD8 lymphocytes. This reduction occurred gradually, but changes in actual values between each time point and baseline were strongly significant (P = .001 at the end of the study compared with the baseline). A strong reduction (P = .001) in cell-associated ceramide levels was found at the end of the study. In general, HIV-1 viremia increased slightly. No toxicity related to L-carnitine therapy was observed and dose reductions were not necessary. In HIV-1–infected subjects, long-term infusions of L-carnitine produced substantial increases in the rate and absolute counts of CD4 and, to a lesser degree, of CD8 lymphocytes. This was paralleled by a reduced frequency of apoptotic cells of both subgroups and a decline in the levels of ceramide. No clinically relevant change of HIV-1 viremia was observed.

We have carried out a large prospective study of the frequency ofH. pylori infection and HIV-1 status in a community of ex-drug abusers including subjects with (N=210) and without (N=259) upper gastrointestinal symptoms, endoscopy and serology. Control groups were patients with upper gastrointestinal symptoms not at high risk of HIV-1 infection (N=219) and asymptomatic blood donors (n=322).H. pylori was present in 52% of symptomatic community resident having endoscopy and 55% of the control patients with symptoms but not at high risk of HIV-1 infection.H. pylori was less common in HIV-1-positive patients (40%) than those who were negative (66%;P<0.001). In patients with AIDS (33%), the frequency ofH. pylori infection was reduced compared to HIV-1-positive patients without AIDS (53%;P=0.05). All the residents with AIDS had upper gastrointestinal symptoms. In community residents, peptic ulcer was always associated withH. pylori infection. ByH. pylori serology, there was no difference in the frequency of infection in asymptomatic residents (56%) whether HIV-1 positive (55%) or HIV-1 negative (58%) compared with those residents with symptoms. Overall,H. pylori was less common in HIV-1-positive residents (49%) than those who were HIV-1 negative (61%;P<0.05). This difference was due mainly to the low frequency of infection in residents with AIDS (33%).H. pylori infection is common in HIV-1 positive patients, and only slightly reduced when compared with at-risk HIV-1-negative subjects. Peptic ulcer is associated withH. pylori in HIV-1 infection. Serology is a reliable marker ofH. pylori infection in HIV-1-positive patients, including those with advanced disease.

Background Infection with human immunodeficiency virus type 1 (HIV-1) causes progressive immune deficiency, the acquired immunodeficiency syndrome (AIDS), and death. Mortality, however, particularly with causes other than AIDS, deserves further study. A retrospective cohort study among drug users in Italy was performed to estimated absolute and proportional mortality rates due to AIDS and other causes, with or without HIV-1 infection. Methods All subjects who enrolled between January 1980 and July 1990 in the drug treatment programme in the Province of Bologna, Italy, were included in the cohort. Each subject was categorized for HIV-1 antibody status (positive, negative, untested), vital status (in 1990 by national surveillance), and causes of death (by death certificate). Data were analysed with actuarial and time-dependent covariate methods. Results There were 332 deaths among 4962 drug users who were followed for 21 130 person-years. This mortality rate (1.57 per 100 person-years) was increased 18-fold compared to the general population. Actuarial 10-year mortality estimates were 28.2% for the 2040 HIV-1 positive subjects, 12 1% for the 1859 HIV-1 untested subjects, and 2.5% for the 1063 HIV-1 negative subjects. AIDS contributed to 150 deaths, followed by drug overdose (64 deaths) and trauma (39 deaths). Compared to others in the cohort, mortality with AIDS and non-AIDS causes was reduced for HIV-1negative subjects. In contrast, mortality for HIV-1 positive subjects was increased with AIDS, trauma, overdose, various bacterial infections, hepatitis, and cirrhosis. Conclusions Mortality with HIV-1 infection was associated not only with opportunistic infections and malignancies but also with competing causes of death, particularly hepatic disease. Further investigation is needed to clarify whether alcohol, analgesics, hepatitis viruses, or other agents have enhanced hepatotoxicity for HIV-1 infected patients.

Although the association among bacterial pneumonia, human immunodeficiency virus (HIV) infection, and injection-drug use seems to have been well established, accurate estimates of the risk of community-acquired pneumonia among HIV-positive and HIV-negative injection-drug users (IDUs) are still needed. To estimate the incidence of pneumonia in a community of former IDUs, we followed 4,236 persons between 1991 and 1994; 1,114 (26.3%) were HIV-positive and 3,122 (73.7%) were HIV-negative. All patients were evaluated for pneumonia by standard criteria, a serum sample was obtained from each participant at least once a year, and laboratory values were monitored. Overall, 149 episodes of pneumonia occurred among HIV-positive patients and 61 among HIV-negative patients; incidence rates were 90.5 and 14.2 (per 1,000 person-years), respectively. The most common etiologic agents were Streptococcus pneumoniae, Chlamydia pneumoniae, and Haemophilus influenzae. Among the HIV-positive former IDUs, there was a 1.37-fold increase in the relative risk of pneumonia for every decrease of 100/mm3 in the CD4 cell count (95% confidence interval, 1.16–1.61). The incidence of community-acquired pneumonia was markedly higher among HIV-positive participants than among HIV-negative ones, a finding similar to that concerning the general population.

The identification of hepatitis C virus (HCV) in semen remains controversial and that of hepatitis G virus (HGV) or GB virus C (GBV-C) has never been investigated. Serum and semen from 90 anti-HCV-positive drug users were tested (27 infected with HIV) for HCV and HGV/GBV-C RNAs by polymerase chain reaction (PCR) assay, hybridization, and sequence analysis. Semen was processed into round cells, seminal plasma, and spermatozoa. Fifty-six patients were HCV-viremic, but HCV-RNA was not identified in their seminal fractions. However, PCR inhibitors were found in the semen of 34 of these men. Twenty-eight patients had HGV/GBV-C RNA in their blood and for 24 of them, ejaculates were available for analysis. HGV/GBV-C RNA was found in the seminal plasma of 6 of 12 samples free from PCR inhibitors. These results agree with the low risk of sexual transfer of HCV and provide preliminary evidence for the presence of HGV/GBV-C in semen.