AIDS epidemiology: the past ten years, the next ten years.

PIP: This article assesses the current seroprevalence of HIV worldwide, examines the patterns of infection over the past 10 years, and discusses the future impact of HIV. According to the World Health Organization (WHO), 8 million people have become infected with HIV since the early 1980s. As of November 1990, WHO estimates that some 800,000 people have developed AIDS. 54% of the HIV infections have occurred in Africa, 35% in the Americas, and 8% in Western Europe. The main HIV transmission routes are: 1) sexual intercourse with an infected partner (accounting for 75% of all infections); 2) HIV-infected blood or blood products, which include blood transfusions (5%), IV drug use (10%), and other needle (0.1%); and 3) perinatal transmission from infected mother to infant (10%). The article describes the 3 patterns of HIV infection so far: 1) In industrialized countries and in Latin America, HIV infections appeared in the early 1980s among homosexual men or IV drug users and then spread to the heterosexual population; 2) In Eastern and Central Africa, where heterosexual sex has been the main transmission route, infections began in the late 1970s; 3) In the rest of the world, HIV was not introduced until the mid-1980s, and because of the low prevalence rate, the main transmission route has not yet been determined. By the year 2000, WHO expects some 15-20 million HIV infections among adults and some 5-6 million AIDS cases among adults. In some industrialized countries, AIDS could become the leading cause of death among 20-40 year olds during the 1990s. At the same time, AIDS will have a devastating effect on sub-Saharan Africa's urban population, which will see a great increase in child mortality rates and in the number of orphaned children.^ieng

Behaviour of different clinical, immunological and serological parameters observed in a group of HIV positive patients during a 12 month treatment period with zidovudine.

During a 12 month open clinical trial, 14 patients (6 with AIDS, 2 with ARC and 6 with PGL) were continuously administered a daily 1200 mg dose of Zidovudine. Clinical course was correlated with a number of serological (HIV p24 antigen, p17 and p24 antibodies) and immunological (CD4 cell counts, serum neopterin and beta 2-microglobulin levels) parameters. All patients survived until the end of the trial: none developed major opportunistic infections, but 5 required an average of 7 blood transfusions each. Disappearance of p24 Ag was observed in 4 out of 7 patients, although with a subsequent reappearance in 3; moreover, changes of p24 Ag and HIV core Ab profiles were generally paralleled by neopterin and, to a lesser extent, by CD4/neopterin ratio variations. In the long run, significant differences between baseline and end-point results were shown by neopterin, but not by CD4 cell counts and beta 2-microglobulin levels. Efficacy of Zidovudine therapy seemed to be mainly related to clinical, but even more so, to immunological and serological status at baseline; in fact, severe clinical deterioration was observed in 2 patients who had an already low CD4/neopterin ratio from the beginning, coupled with a p24 Ag positivity and a negativity of both anti-p17 and -p24. Conversely, a stable clinical condition was observed in those patients in whom the reverse was true.

CD4+:neopterin ratio correlates with p24 antigenaemia in HIV infected patients.

In an effort to improve the Walter Reed Staging System (WR), which mainly relies on immune depletion parameters, by introducing viral replication and T-cell activation markers, we examined by p24 antigenaemia and serum neopterin levels (SNL) 72 HIV positive PGL, ARC and AIDS patients (11 of whom classified as WR 2, 21 as WR 3, 16 as WR 5 and 24 as WR 6). While CD4 cell counts, already weakly correlating with the WR itself, did not significantly differ between p24 antigen (p24 AG) positive and negative patients, striking differences between the two groups, especially in PGL patients (p less than 0.0001), were found as far as SNL was concerned. In fact, SNL values, fluctuating around 10 and 30 nmol/l, respectively, in p24 Ag positive and negative patients regardless of their WR allocation, seemed rather to reflect, as global means of any given class, prevalence rate of p24 Ag positivity. We suggest, therefore, to use CD4/SNL ratio (R) for HIV infection and disease staging, as it not only may represent a compromise index between cellular immune depletion and T-cell activation, but also seems to take into account the viral replication component, already shown to be an important predictive marker of disease progression.

Single-dose fosfomycin trometamol versus multiple-dose cotrimoxazole in the treatment of lower urinary tract infections in general practice. Multicenter Group of General Practitioners.

A randomized trial, comparing a single dose treatment of fosfomycin trometamol (FT, 3 g) versus a 3-times daily regimen of cotrimoxazole (CTX, 960 mg) was carried out in women with uncomplicated urinary tract infections. Of 36 evaluable patients, 19 were treated with FT and 17 with TMP. The bacteriological results after 4 weeks of follow-up were in the FT group (n = 19): cure in 17 (89%), and failure in 2 (11%). For the CTX group (n = 17) the results were cure in 13 (76%), and failure in 4 (24%). Adverse events were reported in 3 patients on FT (2 diarrhoea, 1 epigastralgia) and in 2 on CTX (1 stain rash, 1 asthenia).

HIV-related severe thrombocytopenia in intravenous drug users: prevalence, response to therapy in a medium-term follow-up, and pathogenetic evaluation.

Severe thrombocytopenia (TP) accounted for 5.3% of cases in a consecutive series of 380 HIV-infected intravenous drug users (IVDUs) at presentation. Forty-one of 53 subjects with severe TP showed haemorrhages and were treated as follows: ten were splenectomized, 17 were given high-dose intravenous immunoglobulins (HDIg), and 10 received anti-Rh(D) immunoglobulins (anti-Rh Ig). Splenectomy induced a complete clinical response in all cases: four out of 10 patients maintained platelet counts greater than 100 x 10(9)/l. HDlg gave a good clinical response in all patients, but eight out of 17 suffered haemorrhages during the follow-up and recall treatments were necessary. Six out of 10 patients treated with anti-Rh lg maintained platelet counts greater than 30 x 10(9)/l, but in two cases the treatment was interrupted because of severe haemolysis. No patient progressed to overt AIDS during the follow-up. Splenectomized patients in particular did not show adjunctive risks of worsening of the HIV-related clinical picture. A platelet kinetic study performed in 20 patients with severe HIV-related TP suggests a possible role for platelet sequestration in TP of HIV-infected IVDUs, in which a liver involvement is very frequent.

A trial with ribavirin in patients with AIDS or AIDS-related complex.

A therapeutic trial is described which concerns 6 patients with AIDS and 6 patients with ARC who were submitted to a 6 month course of Ribavirin. Ribavirin was administered orally as the following doses: 3.000 mg daily the first week, 2.000 mg daily the second 2 weeks, and 1.000 mg daily up to completion of the 6 months period. No major side-effects were recorded; only a transient anemia was observed in almost all patients at the higher dose; none of them, however, required to be transfused. No improvement was shown by any of the 6 AIDS patients, neither clinically nor according to laboratory test, whereas all 6 patients with ARC experienced a sense of well-being, a clearing of their symptoms and an average weight gain of about 2.5 kg. No significant changes, though, were recorded as for their immune parameters. A remarkable drop of aminotransfereas was also observed in 4 of the patients, who were affected with chronic hepatitis as well. We conclude that additional, if any, Ribavirin trials should be carried out only in ARC patients.

T-lymphocyte subsets and delayed type hypersensitivity as classification parameters for HIV infection among drug-addicts.

HIV selectively infects T helper lymphocytes, which play an essential role in cell-mediated immunity mechanisms. Impairment of these mechanisms can be evaluated, other than by clinical parameters, by testing lymphocytic subsets and cutaneous delayed type hypersensitivity. All these indices are used in the Walter Reed Foundation (WR) staging system, which includes the different stages of HIV infection. In our study we investigated the above mentioned parameters in a series of 180 HIV positive PDAs. A classification of the same patients according to WR's criteria was also designed. Of our patients, 46.1% resulted normoergic, 27.2% hypoergic and 26.7% anergic. Of all normoergic subjects, 83.7% (with more than 400 OKT4+ cells/mmc) could be assigned to the WR2 and 16.3% (with less than 400 OKT4+ cells/mmc) to the WR3 staging group. Among the hypoergic patients, only 34.7% were assignable to the WR4 group, whereas the majority (65.3%) had more than 400 OKT4+ cell/mmc. Even among the anergic group, 62.5% did not fit the WR5 stage, exhibiting an OKT4+ level higher than 400/mmc. In the latter 2 groups (referred to as D and E), T helper lymphocyte counts were performed at regular intervals; however, only the ones followed-up for at least 6 months were evaluated. OKT4+ cells were shown to decrease more frequently and more rapidly in the anergic than in the hypoergic patients, which points to cutaneous anergy as representing an early sign of impairment of cell-mediated immunity.

Role of PMN's candidicidal activity in the pathogenesis of AIDS-related systemic candidiases.

Phagocytic and fungicidal activity towards C. albicans spores were tested in 9 patients with AIDS-Related Complex (ARC), but without Candida infections, and in 13 patients with AIDS and deep candidiasis. No significant differences were observed between the two mentioned groups as far as PMN's phagocytosis and killing were concerned. PMN's migration in response to a "non-mycotic" chemoattractant was defective in both groups; although, from this point of view, patients with candidiasis were more severely affected. A significant difference was noted, instead, as far as mean T helper values were concerned; in fact, their number was significantly lower in patients with systemic candidiasis than in those with ARC or even AIDS, but oesophageal candidiasis only. In conclusion, defective PMN's activity towards C. albicans spores, as observed in vitro, does not seem in itself to predispose AIDS patients to candidiasis in vivo; mycoses may be rather due to defects of cell-mediated immunity as a whole.

Milan as possible starting point of LAV/HTLV III epidemic among Italian drug addicts.

Sera collected between 1978 and 1985 from 716 parenteral drug-addicts admitted to our Clinic with viral hepatitis were tested for antibodies to HTLV III. None of the patients was showing symptoms suggestive of LAV/HTLV III infection at the time of sera collection. Positivity for HTLV III antibody was found and confirmed (by ELISA) in 212 subjects (29.6%). The earliest positivity appeared in a serum sample collected in February 1979. These and other data point to Milan as to the actual source of the Italian PDAs-linked LAV/HTLV-III epidemic.

Clinical and epidemiological aspects of the first 50 cases of AIDS in Milan.

Between April 1984 and December 1985, 50 patients diagnosed as AIDS were observed in our Clinic. Risk factors were homosexuality in 21 cases (42%), drug addiction in 20 (40%), homosexuality and drug addiction in 3 (6%), haemophilia in 1 (2%). In the remaining 5 cases the infection was acquired by vertical transmission in 2 (4%), by promiscuous heterosexual intercourse in 2 (4%) and by a single blood transfusion in 1 (2%). Kaposi's sarcoma (KS) was the main clinical feature in 8 patients, although associated with opportunistic infections (OI) in 7 of them. A total of 91 different OI were diagnosed with a noteworthy prevalence of mycotic infections compared with OI due to other micro-organisms: 40 deep mycoses by Candida albicans, and 5 cryptococcoses. Pneumocystis carinii pneumonia (PCP) was diagnosed in 20 patients. Our data differ from the ones collected in the USA both epidemiologically, since we observed a greater incidence of AIDS in drug-addicts than in homosexuals and clinically, since in Italy a lower rate of neoplastic disease and, conversely, a higher rate of OI other than PCP are reported.

Albendazole in the treatment of cystic hydatid disease.

Four cases of cystic hydatid disease treated with albendazole are described. The first patient had previously undergone surgical treatment with only partial removal of her hepatic cysts. The size of the remaining cyst resulted remarkably reduced after three courses of the drug. The second patient had recurrent hydatid disease involving the lumbar spine. After therapy, an evident diminution in the size of the cyst was detected. Two patients (one with a partially calcified cyst of the liver, the other one with multiple pulmonary lesions) did not show any objective evidence of improvement. Failures were probably due to the presence of calcified or thick-walled cysts. In all the patients, neither side-effects were observed, nor recurrences were noted during a 2 years' follow-up. In cystic hydatid disease, whenever radical surgical procedures are impracticable, albendazole treatment can achieve significant clinical results.