Didanosine (ddI) associates with increased liver fibrosis in adult HIV-HCV coinfected patients.

The role of exposure to antiretrovirals (ARV) and serum matrix metalloproteases (MMPs) on liver fibrosis (LF) progression in human immunodeficiency virus (HIV) mono or HIV- hepatitis C virus (HCV) coinfection is unclear. Thus, 213 Caucasian adult HIV-infected patients were studied, 111 of whom had HCV-coinfection and 68 were HCV-monoinfected. Patients with ethanol consumption >50 g/day, hepatitis B coinfection, non-infective liver diseases or HAART adherence <75% were excluded. LF was assessed by transient elastometry (TE, Fibroscan). Serum levels of MMPs (MMP -1,-2,-3,-8,-9,-10 and -13) and their tissue inhibitors (TIMP-1,-2 and -4) were measured by ELISA microarrays. Associations with LF were statistically analysed. Protease inhibitors, usually administered to patients with advanced LF were excluded from the analysis. Increased LF was significantly associated with d4T (P = 0.006) and didanosine (ddI) use (P = 0.007), months on d4T (P = 0.001) and on ARV (P = 0.025), duration of HIV (P < 0.0001) and HCV infections (P < 0.0001), higher HIV (P = 0.03) and HCV loads (P < 0.0001), presence of lipodystrophy (P = 0.02), male gender (P = 0.02), older age (P = 0.04), low nadir (P = 0.02) and current CD4(+) T-cells (P < 0.0001), low gain of CD4(+) T-cells after HAART (P = 0.01) and higher MMP-2 (P = 0.02) and TIMP-2 serum levels (P = 0.02). By logistic regression the only variables significantly associated with increased LF were: use of ddI (OR 8.77, 95% CI: 2.36-32.26; P = 0.005), male gender (OR 7.75, 95% CI: 2.33-25.64, P = 0.0008), HCV viral load (in log) (OR 3.53, 95% CI: 2.16-5.77; P < 0.0001) and age (in years) (OR 1.21, 95% CI: 1.09-1.34, P = 0.0003). We conclude that only higher HCV viral load, older age, male gender, and use of ddI associated independently with increased LF in our study.

Long-term augmentation therapy with alpha-1 antitrypsin in an MZ-AAT severe persistent asthma.

A young Caucasian female with severe bronchial asthma and Alpha1-antitrypsin (AAT) deficiency, MZ phenotype, experienced a quick and severe limitation of her physical capacity, which negatively affected her psychological state and social life, though she was under a strong antiasthmatic treatment. Given her declining health status and the significant chronic corticoid administration-related side-effects (including high reduction of muscle mass and bone density), a clinical trial with commercial intravenous AAT was proposed by the patient's doctors, and accepted by the Spanish Ministry of Health, although it this therapy was not approved for MZ phenotypes yet. This new therapy quickly stopped lung function decline rate, dramatically reduced the number of hospital admissions of the patient, suppressed the oral administration of prednisone, reversed the corticosteroid-related health adverse effects, significantly improving her quality of life. Thus, although AAT replacement therapy is not approved nor indicated for the treatment of bronchial asthma in MZ patients, its favourable effects observed in this isolated case support the hypothesis that bronchial asthma could be due to pathogenic mechanisms related to a protease-antiprotease imbalance, what which could open new perspectives for future research on the field.

[Serology of the human immunodeficiency virus in saliva]. / Serología del virus de la inmunodeficiencia humana en saliva.

BACKGROUND: The presence of immunoglobulins in saliva has allowed it to be proven that they are specific against certain antigens. Antibodies to the human immunodeficiency virus (HIV) have been observed in saliva. The aim of this study was to evaluate the detection of the same by commercial enzymoinmmunoassay (EIA) and standardize the technique. METHODS: In 78 intravenous drug user patients the presence of antibodies against HIV in serum and saliva were determined by recombinant EIA (Abbott HIV-1/HIV-2 recombinant EIA). The determinations in saliva were made taking volumes of 10 and 50 microliters. RESULTS: In 43 patients the presence of antibodies against HIV-1 was demonstrated in serum, 42 of which were positive in saliva in the determination with 50 microliters and 16 with 10 microliters. No false positives were reported. With the use of 50 microliters of saliva the test showed a sensitivity of 0.98, specificity of 1, predictive value of a positive result of 1, predictive value of negative result of 0.98 and diagnostic efficacy of 0.99. CONCLUSIONS: The determination of antibodies against HIV in saliva in intravenous drug users is a highly sensitive and specific method with the use of volumes of 50 microliters in the tests.

[Antiphospholipid antibodies in human immunodeficiency virus infection]. / Anticuerpos antifosfolípido en la infección por el virus de la inmunodeficiencia humana.

BACKGROUND: The frequency, clinical significance and prognosis of the lupic anticoagulant and the anticardiolipin antibodies were analyzed in patients with the human immunodeficiency virus infection. METHODS: A group of 34 consecutive patients seropositive to HIV with lupic anticoagulant was studied in relation with 75 seropositive subjects without circulating anticoagulant and a control group of plasma of 23 seronegative individuals. The lengthening of thromboplastin time (relation > 1.3) was used as a screening test. The anticardiolipin antibodies IgG were studied by commercial enzymoimmunoassay. RESULTS: Lupic anticoagulant was detected in 21% of the patients with AIDS and in 3% of the seropositive patients without AIDS. The anticoagulant was found in 13 of 53 cases with tuberculosis, in 8 of 57 with pneumonia by Pneumocystis carinii, in 4 of 32 with bacteremia and in 3 out of 8 with lymphoma. In another six patients other minor processes and/or HIV seropositivity were coexistent. Thrombosis was not seen in any case, and the rate of thrombocytopenia (18%) was that to be expected in this population. The patients with anticoagulant had a greater prevalence to developing AIDS, opportunistic infections and tuberculosis with respect to the seropositive group without anticoagulant, however, no differences were observed in the prevalence and levels of anticardiolipin antibodies and other nonspecific autoimmune phenomena. Periodic follow up of the patients with anticoagulant demonstrated persistence of the anticoagulant in 31% and reappearance of the same in 23% with new infections. CONCLUSIONS: No correlation was found between the different antiphospholipid antibodies in the patient infected by the human immunodeficiency virus. Low titers of anticardiolipin antibodies are indicative of disease progression.

[Replication indexes of the human immunodeficiency virus: predictive value of viral culture and blood antigens]. / Indices de replicación del virus de la inmunodeficiencia humana: valor predictivo de los cultivos virales y de la antigenemia.

BACKGROUND: To investigate the relation between markers of load and replication of the HIV [viral culture in plasma and in mononuclear cells of peripheral blood (MCPB) and antigen p24 (p24Ag) with the number of CD4+ cells and the prognosis of the patients. METHODS: A retrospective study was performed in 188 patients who were analyzed and followed over a mean period of 431 days. The criteria of clinical progression (AIDS related complex, and new opportunistic infections), immunologic progression (CD4+ < 0.1 and < 0.05 + 10(9)/l) and death. Cocultures of HIV in free plasma and in MCPB were performed with the detection of complete AgHIV in the supernatant of the culture being used for analysis. Circulating p24Ag was determined by an ELISA technique without previous dissociation of the immunocomplexes. RESULTS: HIV cultures in plasma, in MCPB and p24Ag were positive in 27, 48 and 33% of the patients, respectively. The sensitivity of the indexes increased in agreement with the clinical progression of the patients and was inversely proportional to the depletion of the CD4+ lymphocytes (79% of the patients with CD4+ lymphocytes < 0.05 x 10(9)/l presented positive HIV culture in plasma). Viremia in plasma and to a lesser measure p24Ag correlated with variables recognized as bad prognosis and were found to be predictive of unfavorable evolution. Multivariate analysis demonstrated that pertenence to a symptomatic group and the presentation of a number of CD4+ lymphocytes of less than 0.2 x 10(9)/l were independent factors associated to the positivity of the viral culture in plasma and p24Ag. The culture positive in MCPB was principally related with the volume of blood analyzed. The risk of death was 6.38 fold greater in the presence of a positive plasma culture and 2.02 fold greater in the presence of positive p24Ag. In contrast, the unquantified positive HIV culture in MCPB showed no statistical significance in relation with patient survival. CONCLUSIONS: Positive HIV culture in plasma was the greatest prognostic index in patients with a number of CD4+ lymphocytes less than 0.2 x 10(9)/l. Unquantified cell culture had no predictive significance. To establish the prognosis of patients, the indexes of viral replication should not be used in isolation.

[The prevalence of HCV antibodies in 3 groups with distinct patterns of sexual activity]. / Prevalencia del antiVCH en tres grupos con distintos patrones de actividad sexual.

We studied the prevalence of antibodies to hepatitis C virus (anti-HCV) among 164 heterosexual partners of anti-HCV-positive subjects, 131 prostitutes and 52 homosexual men. 6.7% of heterosexual monogamous partners had anti-HCV; the seropositivity rate was associated with a long-term sexual practice and with age. Of the 131 prostitutes, 6 (4.6%) had anti-HCV; there were significant associations in patients positive for anti-HCV, with a history of parenteral drug addiction. 11.5% of homosexual men were anti-HCV positive; there were significant associations with positivity for antibodies to HIV, intravenous drug abuse and with the number of sexual partners. We concluded that the HCV may be transmitted by sexual route, but the high seroprevalence among prostitutes and homosexuals may be explained by other parenteral mechanisms.

[Simultaneous acute infection with human immunodeficiency virus and cytomegalovirus]. / Infección aguda simultánea por virus de inmunodeficiencia humana y citomegalovirus.

2 cases of simultaneous acute infection caused by HIV and CV that showed clinical features of infectious mononucleosis with spontaneous resolution and good evolution is presented. After 12 months following them up, both are symptom free carriers of HIV and without clinical features of CV infection. These cases had a good evolution, which is contrary to what is described in other medical literature.

[Necrotic leukoencephalitis, a new infrequent form of presentation of HIV encephalopathy]. / Leucoencefalitis necrotizante, una forma infrecuente de presentación de la encefalopatía por VIH.

A case of a female infected by HIV whose first manifestation was a focal defect of the motor function caused by a brain lesion shown in the CT scan and NMR as a hemispheric mass with discreet expansive effect and central necrosis. The histologic study showed a necrotic leukoencephalitis related to HIV as etiologic agent. We point out the difficulties in diagnosing and treating this disease.