Clinical characteristics and prognostic value of acute retroviral syndrome among injecting drug users. Italian Seroconversion Study.

OBJECTIVE: To estimate the frequency of acute retroviral syndrome associated with HIV infection among injecting drug users (IDU), and to determine the extent to which acute retroviral syndrome predicts a faster rate of progression to AIDS and immunosuppression in this population. DESIGN: Prospective study of HIV seroconverters (median follow-up, 50.5 months). SETTING: Sixteen clinical centres throughout Italy established to study the natural history of HIV infection. PATIENTS: Three hundred and ninety-one IDU for whom the date of HIV seroconversion was established with a 9-month precision. MAIN OUTCOME MEASURES AND METHODS: Incidence of acute retroviral syndrome with signs and symptoms that included fever (temperature > 38 degrees C) occurring within 6 months prior to the time of first positive HIV test, progression to AIDS, crude and adjusted relative hazard of AIDS using survival analysis techniques, and trajectories of CD4+ cell counts using a piece-wise linear regression model incorporating the degree of dependency of within-person measurements. RESULTS: Of 391 HIV seroconverters, 39 (10.0%) were diagnosed with acute retroviral syndrome. During follow-up, 13 seroconverters with acute retroviral syndrome and 24 asymptomatic seroconverters developed AIDS. The Kaplan-Meier estimates for the cumulative AIDS incidence during 4.5 years of follow-up were 26.8 and 6.5%, respectively; the relative hazard of developing AIDS for acute retroviral syndrome was 5.59 (95% confidence interval, 2.79-11.20) after adjustment for age, sex and year of seroconversion. Although CD4+ level within the first year from seroconversion was similar, the rate of CD4+ cell decline after 1 year from seroconversion was faster in individuals with acute retroviral syndrome than in those without this syndrome (P < 0.001). CONCLUSIONS: Among HIV-infected IDU, a distinct acute retroviral syndrome is apparent and associated with a faster rate of clinical progression to AIDS and HIV-related immunosuppression.

Spread of hepatitis C virus among sexual partners of HCVAb positive intravenous drug users.

Recent studies suggest that the seroprevalence of hepatitis C virus antibodies (HCVAb) among sexual partners of those who are HCVAb positive is higher than in the general population. Moreover some studies seem to indicate that transmission of hepatitis C virus (HCV) occurs more readily when there is HIV infection in the couple. We studied the prevalence of HCVAb seropositivity among the regular sexual partners of 84 HCVAb positive intravenous drug users (IVDUs), by means of ELISA confirmed by radio immuno-adsorbent assay, 11 generation (RIBA II). The couples were subdivided into three groups: group 1: 30 HIV negative IVDUs and their HIV negative partners (HIV-/HIV-); group 2: 47 HIV positive IVDUs and their HIV negative partners (HIV+/HIV-); group 3: seven HIV positive IVDUs and their HIV positive partners (HIV+/HIV+). The seroprevalence of HCVAb among the partners of IVDUs was 28.6% in the couples of group 3, 12.8% in the couples of group 2 and no partner was positive among the couples of group 1. There was no statistically significant difference in HCV transmission between the couples who never used a condom and those who always used one. The couples of group 1 never used a condom. We found HCVAb seropositivity only in the partners who were in couples in whom HIV was present. We did not demonstrate that sexual intercourse is a means of HCV transmission because none of the HIV-/HIV- couples of group 1 used a condom and no partner was HCVAb positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary deposition of aerosolised pentamidine using a new nebuliser: efficiency measurements in vitro and in vivo.

The therapeutic efficacy of nebulised pentamidine in the prophylaxis of Pneumocystis carinii pneumonia (PCP) depends on the absolute pulmonary deposition of the drug. We studied the performance of a new nebuliser (Pentasave) by comparison both in vitro and in vivo with a standard nebuliser (Respirgard II). In vitro, deposition of pentamidine labelled with technetium-99m human serum albumin was measured indirectly by capturing inhaled particles on an absolute filter and measuring radioactivity with a gamma camera. The nebulisers were initially assessed with a pentamidine dose of 100 mg in 5 ml at 44 psi and an air flow of 10 l/min for Respirgard II and 16 l/min for Pentasave. Nebuliser output, expressed as the percentage of the initial nebuliser radioactivity captured by the inhalation filter, was 15% +/- 2% (mean +/- SD) for Respirgard II, and significantly increased to 23% +/- 3% for an initial version and to 33% +/- 2% for the final version of Pentasave. Measurements with a gamma camera in a group of ten patients with human immunodeficiency virus infection were made in vivo. The results revealed that pulmonary drug distributions are good using both Respirgard II and Pentasave. The literature reports that once-monthly pulmonary deposition of 9 mg pentamidine seems enough to produce prophylactic effects against Pneumocystis carinii. We measured pulmonary pentamidine deposition of 20.22 +/- 4.31 mg (mean +/- SD) using Respirgard II (with 300 mg in 5 ml) and of 16.00 +/- 7.18 mg using Pentasave (with 150 mg in 6 ml). These findings show that the therapeutic dose of pentamidine (9 mg) was widely exceeded with both nebulisers. Further investigations might demonstrate that about 200 mg and 125 mg pentamidine for Respirgard II and Pentasave, respectively, will achieve a pulmonary deposition of therapeutic dose, allowing significant savings in terms of drug and expense.

Man-to-woman sexual transmission of HIV: longitudinal study of 343 steady partners of infected men.

To study incidence and risk factors of heterosexually transmitted HIV infection, we followed a cohort of 343 seronegative women, stable, monogamous partners of infected men whose only risk of acquiring HIV was sexual exposure to the infected partner. Nineteen seroconversions occurred in 529.6 person years (py) of observation, yielding an incidence rate of 3.6 per 100 py. The incidence rate was 7.2 per 100 py among women who did not always use or never used condoms and 1.1 among those who always used them [relative risk (RR) 6.6, 95% confidence interval (CI) 1.9-21.9]. Anal sex was associated with a risk increase in only those women not always using condoms (RR 1.4, 95% CI 0.4-4.8). No seroconversions were observed among 22 women using oral contraceptives. One of the women using intrauterine devices seroconverted. In couples who did not always use condoms, seroconversions occurred more frequently in partners of men with symptomatic diseases, with a low CD4+ cell number (< 400 per mm3) or with a detectable p24 antigen. In couples not always using condoms and where the man had a low CD4+ cell count, the joint presence of blood viral antigens and AIDS symptoms conditioned a fivefold increased risk of seroconversion of the woman (RR 5.4, CI 1.4-20.3). At multivariate analysis, women with longer relationships (> or = 1 year) showed a lower risk of seroconversion (RR 0.3, CI 0.1-0.8), and those partners of men positive for p24 antigen in serum had an increased risk of seroconversion (RR = 4.0, CI 0.1-0.8).

Comparison of two dose regimens of zidovudine in an open, randomized, multicentre study for severe HIV-related thrombocytopenia.

OBJECTIVE: To compare the effect of two dose regimens of zidovudine in the treatment of severe HIV-related thrombocytopenia (TP). DESIGN: Eighty-four patients with severe HIV-related TP and platelet counts < 50 x 10(9)/l were enrolled in an open study at six centres. Patients were randomized into two groups to receive zidovudine (group A, 500 mg per day; group B, 1000 mg per day) for 6 months. METHODS: Platelet counts were determined monthly and patients categorized as complete responders (CR; platelets > 100 x 10(9)/l), partial responders (PR; platelets > 50 to < 100 x 10(9)/l), or failures (F; platelets to < 50 x 10(9)/l). CD4+ and CD8+ lymphocytes, HIV antigenaemia, beta 2-microglobulin, white blood cells, mean cell volume and haemoglobin were also determined. RESULTS: Seventy-one patients (35 and 36 in groups A and B, respectively) completed the study; 11.4% of group A patients were CR and 45.7% PR; 38.9% of group B were CR and 33.3% PR. Increase in mean platelet counts was dose-related, more rapid in the higher dose group and remained significantly higher after 6 months of treatment (56.4 x 10(9)/l in group A versus 98.2 x 10(9)/l in group B; P < 0.01). CONCLUSIONS: The results confirm the efficacy of zidovudine in the treatment of severe HIV-related TP. The average for CR and PR in the two groups was 64.8%; the higher dose of zidovudine was more effective at increasing platelet counts.

IgA as a marker of clinical progression among HIV-seropositive intravenous drug users.

The recognition of markers of progression towards disease in carriers of HIV is important in order to identify those who will develop AIDS and to start antiviral treatment at the appropriate time. Most studies of potential markers of progression have been made on homosexual men and haemophiliacs. We studied a population of 87 intravenous drug users (IVDUs), recruited between May 1984 and May 1986, in order to determine the usefulness of CD4 and CD8 counts as well as IgG, IgM and IgA values in predicting progression to AIDS. Eight persons developed AIDS during a median period of 44 months. Overall, the mean IgA value was lower in HIV-seropositive IVDUs than in HIV-negative IVDUs and in HIV-negative persons not using IV drugs and who acted as controls. Even so, a concentration of IgA > 2.5 g/l at enrollment was the best predictor of progression to AIDS. This finding suggests that a raised concentration of IgA may be an important early marker of progression towards disease in this population.

The natural history of HIV infection in intravenous drug users: risk of disease progression in a cohort of seroconverters.

A multicentre cohort study was carried out to estimate the incidence of AIDS and HIV-related conditions in newly infected intravenous drug users (IVDU). The enrollment criteria included the identification of the seroconversion time. Two hundred and five subjects entered the study, and were followed for a mean of 26 months. Twelve subjects developed clinical AIDS over a 4-year period. The actuarial incidence of AIDS estimated by Kaplan-Meier survival technique was 17.8% by 4 years since seroconversion. The risk of developing AIDS increased significantly after 24 months from seroconversion. Relatively small figures accounted for the lack of statistical association between the risk factors investigated and the disease status.

PIP: The natural course of HIV infection in 205 intravenous drug users (IVDU) presenting at 11 centers in Italy was followed since 1983. Criteria for entering the study were spontaneous attendance at the clinic from January 1983-April 1988; history of IVDU; dated negative HIV test and a positive test not over 18 months later. 13 of the 205 subjects developed AIDS by 30 April 1988, a total of 447.25 person-years, for an overall incidence of AIDS of 2.9% person-years. The clinical presentation was opportunistic infections in 7, wasting syndrome in 5, and encephalopathy in 1. No Kaposi's sarcoma was seen. The incidence of AIDS was 1.5% in the 1st year; 2.9% after 2 years; 9.9% after 3 years and 17.9% after 42-48 months. The risk of AIDS increased significantly 24 months after seroconversion. 11 others developed AIDS-related complex (ARC) in the 4-year period, an incidence of 3.4% person-years. The minor opportunistic infections seen were zona (4 cases), oral candidiasis (2), and hairy leukoplakia (1). 2 subjects had myelopathy. 87 others developed persistent generalized lymphadenopathy (PGL). 45.8% of the group remained asymptomatic. The subjects mean age was 26, and the sex ratio was 4:1 overall, but 12:1 among the AIDS group. The natural history of AIDS in this series closely resembled other reports on male homosexuals.