Cutaneous Adverse Reactions to Highly Antiretroviral Therapy in HIV-Positive Patients.

Adverse drug reactions to highly antiretroviral therapy (HAART) are major obstacles in its success. Although overall mortality from HIV has dramatically declined owing to HAART, these antiretroviral regimens have been associated with a wide spectrum of severe cutaneous reactions. The severity of cutaneous adverse reactions varies greatly, and some may be difficult to manage. To optimize adherence and efficacy of antiretroviral treatment, clinicians must focus on preventing adverse effects whenever possible, and distinguish those that are self-limited from those that are potentially serious. This paper presents the case of a serious cutaneous adverse reaction to Atripla in a HIV-positive 50-year-old Caucasian woman.

Selective neurogenic blockade and perioperative immune reactivity in patients undergoing lung resection.

OBJECTIVE: This double-blind, prospective, randomized, controlled trial examined the effects of thoracic epidural block and intravenous clonidine and opioid treatment on the postoperative Th1/Th2 cytokine ratio after lung surgery. The primary endpoint was the interferon γ (IFN-γ; Th1 cytokine)/interleukin 4 (IL-4; Th2 cytokine) ratio. Secondary endpoints were reductions in pain and incidence of pneumonia. METHODS: Sixty patients were randomized into three groups to receive remifentanil intravenously (remifentanil group, n=20), remifentanil and clonidine intravenously (clonidine group, n=20), or ropivacaine epidurally (ropivacaine group, n=20). Pain was assessed using a numerical rating scale (NRS). Cytokines were measured using a cytometric bead array. RESULTS: Patients in the ropivacaine group (thoracic epidural block) had a significantly lower IFN-γ/IL-4 ratio at the end of surgery than those in the remifentanil group and clonidine group. There were no significant between-group differences in the IFN-γ/IL-4 ratio at other time-points. There were no differences in NRS scores at any time-point. No patient developed pneumonia. CONCLUSION: Intraoperative thoracic epidural block decreased the IFN-γ/IL-4 ratio immediately after lung surgery, indicating less inflammatory stimulation during surgery.

Solitary keratoacanthomas in immunocompetent patients: no detection of papillomavirus DNA by polymerase chain reaction.

The aetiology of keratoacanthoma (Ka) is unknown, but human papillomavirus (HPV) has been implicated in the pathogenesis of this lesion. To evaluate the role of HPV in the development of KA in the general population, 20 tissue specimens were analysed by polymerase chain reaction (PCR). To include a broad range of both cutaneous and mucosal HPV types, PCR was performed with two sets of degenerate primers. No HPV-DNA sequences were detected in any lesions analysed. These results do not support the hypothesis that HPV is involved in the etiology and pathogenesis of the KA in immunocompetent patients.

Antibodies to human herpes virus type 8 (HHV8) in general population and in individuals at risk for sexually transmitted diseases in Western Sicily.

BACKGROUND: Human herpes virus 8 (HHV8) appears to be the primary aetiologic agent of Kaposi sarcoma (KS). To study the distribution of HHV8, a seroepidemiological study was carried out in western Sicily, where a high incidence rate of classical KS is well documented. METHODS: A total of 970 sera of healthy human immunodeficiency virus (HIV) negative individuals of general population (1-70 years old) and 742 sera of individuals in different risk groups for HIV infection were evaluated by means of an indirect immunofluorescence assay able to detect antibodies to lytic and latent HHV8 antigens. RESULTS: Crude seroprevalence to HHV8 antigens was 11.5% in the general population, and it increased significantly with age from 6% under age 16 to 22% after age 50. Significantly higher HHV8 seroprevalence rates were detected among HIV positive and negative homosexual men (62% and 22%, respectively), men who had sex with prostitutes (40% and 29%, respectively); female prostitutes (42% and 30%, respectively), and clients at a sexually transmitted disease clinic (male: 60% and 33%, respectively, female: 63% and 43%, respectively). In contrast, heterosexual intravenous drug users had seroprevalence rates comparable to those found in the general population. CONCLUSIONS: The results suggest that HHV8 infection is widespread in Western Sicily. The high seroprevalence in individuals with high risk sexual activity point to the role of sexual behaviour in the transmission of the infection in adults, whereas the detection of antibodies in younger population (under 16 years old) is suggestive of a non-sexual route of transmission, probably occurring during childhood by close personal contact.

Serological and virological evidence of non-sexual transmission of human herpesvirus type 8 (HHV8).

To evaluate whether or not human herpesvirus 8 (HHV8) can be transmitted through a non-sexual route a serological survey was carried out in a group of 51 catholic nuns. The seroprevalence rate and the geometrical mean antibody titre to anti-latent HHV8 antigen were similar in nuns and in a group of 60 women, matched by age, in the general population (27 vs. 24%; 1028 vs. 1575, respectively). Moreover, by using nested polymerase chain reaction (PCR), HHV8 DNA sequences were detected in 7 of 16 (43.8%) saliva and peripheral blood mononuclear cells (PBMC) from patients with classical Kaposi's sarcoma (KS) and in 3 out of 7 (42%) AIDS-KS patients. None of 5 HIV positive persons who did not have KS tested positive for HHV8 DNA. HHV8 DNA sequences were also detected in 2 of 12 (17%) saliva and 1 PBMC sample out of 12 healthy HHV8 positive individuals (age range: 30-80 years old). This paper suggests that non-sexual transmission of HHV8 is operating in our geographical setting and saliva may be a potential source of HHV8 spreading in the general population.

Inhibition of human immunodeficiency virus 1 (HIV-1) by variant B of human herpesvirus 6 (HHV-6).

Four HHV-6 strains were initially isolated during attempts to observe HIV-1 replication in cultured primary lymphocytes from 48 patients with AIDS. HHV-6 DNA from each strain was extracted from primary cell cultures and amplified using specific primers in a nested polymerase chain reaction (PCR) assay. All HHV-6 strains were classified as B variants by submitting the PCR products to the digestion of two restriction enzymes (Hind III and Bgl II). Since in primary cultures, the appearance of HHV-6 cytopathic effect was followed by a progressive reduction of HIV-1 replication, we tried to reproduce the observed inhibition in vitro. Two HHV-6 strains, used throughout the experiments, showed their ability to suppress HIV-1 replication when the viruses co-infected CD4+T lymphocyte cultures. While the intrinsic mechanism of this finding still remains unclear, the inhibition of HIV-1 replication was observed only when a high multiplicity of infection (m.o.i.) of HHV-6 and a low m.o.i. of HIV-1 were used in dually infected cell cultures. By using a semiquantitative determination of HIV-1 cDNA by PCR, it appears that the inhibition begins in infected cell cultures and, once established, does not allow any further HIV-1 replication.

Distribution of hepatitis C virus genotypes among intravenous drug users. A ten-year study in Palermo, Sicily.

A cross-sectional study was carried out on the sera of 88 active intravenous drug users (IVDU) collected between 1985 and 1986 to evaluate the circulation of HCV genotypes in Western Sicily. The patients were grouped by age and classified by their HIV status. Genotype 3a (48.8% of all cases) was most frequently detected, followed by genotype 1a (20.4%) and type 1b (17.0%). No significant differences in HCV genotype distribution were observed between HIV positive and negative individuals. Next, the HCV genotype distribution found in sera samples of IDVUs drawn between 1985 and 1986 was studied and divided into three age groups. The genotype distribution in the younger group was then compared with samples collected ten years later, between 1995 and 1996, from young HIV negative IVDU individuals. A different distribution between HCV genotypes 3a and 1a was found with a relative, though not significant, increase in the detection of genotype 1a (38%). Finally, sera from six IVDUs obtained at three different times over a ten-year period were genotyped for HCV. None of the subjects showed any change in the genotype found at the first sampling throughout the ten years. The results suggest that a) genotype 1a and 3a are the most common among IVDUs in Western Sicily, b) concurrent HIV infection does not seem to influence HCV genotype and c) infected IVDUs harbor almost exclusively one genotype.

Human herpesvirus type 8 DNA sequences in biological samples of HIV-positive and negative individuals in Sicily.

OBJECTIVE: To evaluate the circulation of a new human herpesvirus (HHV), HHV-8 or Kaposi's sarcoma (KS)-associated herpesvirus in a geographical area where a high incidence rate of classical KS was already present before the appearance of the AIDS epidemic. DESIGN AND METHODS: The study was carried out by analysing: (i) bioptic samples from classic, AIDS-associated KS, and controls; (ii) peripheral blood mononuclear cells (PBMC) from classic KS, HIV-positive subjects with and without KS and healthy HIV-negative individuals; (iii) semen samples from heterosexual HIV-positive and HIV-negative individuals affected or not by KS; and (iv) cervical swabs from HIV-negative healthy heterosexual females. All specimens were tested for the presence of HHV-8 DNA sequences by a two-step polymerase chain reaction. RESULTS: Positive results were obtained in 90% of bioptic samples of classic KS and in 100% of AIDS-associated KS. Viral sequences were also present in 50% of PBMC of subjects with classic KS and AIDS-associated KS, in 10% of AIDS patients without the angiosarcoma and in 11% of healthy HIV-negative individuals. Finally, HHV-8 DNA was detected in 13% of semen of HIV-negative heterosexual individuals and in 10% of AIDS patients without KS. Both PBMC and ejaculates from the same individual gave positive results. No HHV-8 sequences were found in cervical swabs. CONCLUSIONS: HHV-8 is widespread in the general population in Sicily since it was detected in PBMC and semen of heterosexual HIV-negative individuals and is not found only in high-risk groups. The viral load appears to be more elevated in a high-risk population and it may be ascribed to a viral reactivation. The higher incidence rates of KS in Sicily compared with northern Italy and other European countries might be related to the presence of HHV-8 in the general population.

Rare association of human herpesvirus 6 DNA with human papillomavirus DNA in cervical smears of women with normal and abnormal cytologies.

We investigated by nested PCR the possible association of human herpesvirus 6 (HHV-6) and human papillomavirus (HPV) genomes in the cervixes of 109 women with normal and abnormal cytological smears. HPV DNA was detected in 8.33% of 24 women with normal cytologies and in 41.1% of 85 women with abnormal cytologies; the proportion of HPV DNA was directly related to the severity of the lesions. HHV-6 DNA was found in only one patient, who had a cytological pattern of koilocytosis. The HHV-6 genome was classified by restriction enzyme analysis as variant B. The study indicates that detection of the HHV-6 genome in the cervixes of women with a wide spectrum of gynecological complaints is a rare event and rules out the possible association between HHV-6 and HPV genomes in cervical cancer lesions.