Human Immunodeficiency Virus Infection

Human Immunodeficiency Virus Infection

Clinical Significance of Eosinophilia in HIV-infected Individuals

Introduction.—Eosinophilia is a common finding in patients with AIDS. However, there is no research linking this eosinophilia to specific causes, such as parasitic infections or drug reactions. The clinical significance of and factors associated with eosinophilia in HIV-infected subjects were examined retrospectively.

Human Immunodeficiency Virus InfectionMethods.—The study included 42 patients with HIV infection and peripheral eosinophilia. They were matched for the date at which absolute eosinophil counts were first more than 500 cells per cubic millimeter and for CD4 cell counts with 84 patients infected with HIV but without eosinophilia. Clinical factors potentially associated with eosinophilia were compared between the 2 groups.

Result.—The patients with eosinophilia had a median CD4 cell count of 26 cells per cubic millimeter, reflecting late-stage HIV infection. Fifty-two percent of patients with eosinophilia were black, compared with 18% of controls. The case patients were also more likely to have pruritus (50% vs. 20%), and a physician-documented rash (76% vs. 52%). Patients with eosinophilia were more likely to have specific cutaneous diseases, such as eosinophilic folliculitis, atopic dermatitis, and prurigo nodularis. Allergic reactions, parasitic infections, cancer, and adrenal insufficiency—all factors commonly associated with eosinophilia—were no more common in case patients than in controls.

Conclusions.—The finding of peripheral eosinophilia in patients with AIDS is linked to cutaneous diseases. However, it is not associated with allergic reactions, parasitic infections, or other conditions frequently associated with a raised eosinophil count. Thus, the finding of asymptomatic
eosinophilia in a patient with AIDS with cutaneous disease is not an indication for an extensive diagnostic workup.

• In this study, peripheral eosinophilia in individuals infected with HIV was associated with low CD4 cell counts and a high incidence of cutaneous diseases, especially eosinophilic folliculitis and atopic dermatitis. There was no increased incidence of parasitic diseases, drug reactions, collagen vascular disorders, and neoplasms, which are other conditions typically associated with eosinophilia.

UVB Phototherapy Is an Effective Treatment for Pruritus in Patients Infected With HIV

Purpose.—Many patients with HIV infection have chronic, intractable pruritus. A common cause of this problem is eosinophilic folliculitis, although generalized, severe pruritus may occur without primary skin lesions. A number of different treatments have been tried. Ultraviolet B (UVB) phototherapy was evaluated for use in the treatment of HIV-related pruritus that did not respond to other treatments.

Methods.—The study included 21 male patients with HIV infection and intractable pruritus that did not improve with topical corticosteroid or oral antihistamine therapy. Fourteen had eosinophilic folliculitis, and 7 had primary pruritus. All patients had a CD4+ cell count at the time of UVB phototherapy or within 30 days and were able to undergo treatment on a regular basis. The patients received UVB phototherapy 3 times a week, with physician examination after every fifth treatment. Pruritus was scored on a scale of 0-10, with 10 representing severe pruritus.

Results.—At the start of treatment, the patients’ mean CD4 count was 91 cells per µL. Pruritus scores were significantly improved by UVB phototherapy, from a mean of 8.6 to 2.2. Improvement peaked after a mean of 21 treatments, at a cumulative UVB dose of 3,399 mJ/cm2. The results were similar in patients with eosinophilic folliculitis and primary pruritus.

Conclusions.—For patients with HIV-related pruritus, UVB phototherapy can offer significant symptom reduction and improvement in quality of life. The results are consistent with previous studies of UVB phototherapy for eosinophilic folliculitis. This study also shows a favorable response in patients with eosinophilic folliculitis.

 Pruritus in HIV-infected individuals is extremely common and is often severe. Ultraviolet B phototherapy can be a less expensive alternative to psoralen plus ultraviolet A for treating these patients. Although exposure to ultraviolet radiation can be associated with viral activation, previous studies have shown that there is no consistent alteration in CD4 positive cell counts or HIV-1 viral load in patients treated with phototherapy.

Efficacy and Safety of Desensitization With Sulfamethoxazole and Trimethoprim in 48 Previously Hypersensitive Patients Infected With Human Immunodeficiency Virus

Objective.—Sulfamethoxazole-trimethoprim is the first-line approach to primary prevention of Pneumocystis carinii pneumonia and Toxoplasma infection in HIV-positive patients. However, adverse skin reactions are a major problem. These reactions can be managed by treatment throughout the duration of hypersensitivity, rechallenge, or desensitization. Desensitization with sulfamethoxazole-trimethoprim was studied for safety and efficacy in a large cohort of HIV-infected patients. Clinical and biological factors associated with success were evaluated as well.

Methods.—The prospective study included 51 HIV-infected patients with a history of allergy to sulfamethoxazole-trimethoprim, including rash or other cutaneous adverse reactions. These reactions were blamed on sulfamethoxazole-trimethoprim if they occurred within 21 days after the start of treatment, or later if there was no other potentially responsible drug. The study excluded patients with life-threatening reactions, involvement of more than 1 mucous membrane, urticarial rash, or cutaneous rash occurring within 6 weeks before enrollment. It did not exclude patients with fever, pruritus, or involvement of just 1 mucous membrane, however. Desensitization was a 2-day procedure, with the full dose of sulfamethox-azole-trimethoprim (400 and 80 mg, respectively) being reached on day 3. For 3-months after desensitization, the patients were monitored for cutaneous reactions attributable to sulfamethoxazole-trimethoprim. If treatment had to be interrupted during that time, desensitization was considered to have failed. If sulfamethoxazole-trimethoprim was well tolerated after 3 months, desensitization was considered a success. There were 48 evaluable patients.

Results.—At 3 months, 77% of patients were taking sulfamethoxazole- trimethoprim without problems. Daily treatment continued for a median of 16 months. The failure rate was 23%, with 8 of the 11 failures occurring on the first or second day. Desensitization was more likely to be successful in patients with lower CD4+ cell percentages and CD4+-CD8+ ratios.

Conclusions.—Successful desensitization with sulfamethoxazole-trimethoprim in hypersensitive HIV-infected patients is reported. This study achieved a 77% success rate, compared with the 33% to 96% success rates of previous studies. The duration of desensitization does not appear to affect the success rate. It remains to be determined whether rechallenge or desensitization is the best approach for patients with non-life-threatening reactions to sulfamethoxazole-trimethoprim. Although the failure rates are comparable, desensitization may be safer than rechallenge.

 Previous desensitization schedules have been of varying durations, ranging from 5 hours to 20 days and have differed greatly with regard to inclusion criteria, the mode of dose escalation, and the success rate. Desensitization is not entirely safe, and anaphylactoid reactions have been observed.

Oral Hairy Leukoplakia in 71 HIV-Seropositive Patients: Clinical Symptoms, Relation to Immunologic Status, and Prognostic Significance

Background.—Oral hairy leukoplakia occurs almost exclusively in men with HIV infection. Although its presence indicates moderate to advanced immunodeficiency, its value as a marker of prognosis is not known. These investigators evaluated oral hairy leukoplakia as a prognostic marker in HIV patients with oral hairy leukoplakia and in HIV patients without this development.

Methods.—A total of 456 patients with HIV-associated skin disease were identified; 71 of these had oral hairy leukoplakia (15.6%; 65 men, 5 women, and 1 transsexual; median age 35 years). Oral hairy leukoplakia was diagnosed when a lesion had the characteristic appearance, did not rub off, and did not respond to anticandidal drugs. Subpopulations of CD4+ T lymphocytes were measured at baseline and regularly thereafter and survival time was calculated starting with the diagnosis of oral hairy leukoplakia.

Findings.—The 71 patients with oral hairy leukoplakia most often had lesions on the lateral tongue that were white or gray-white, well-defined, adherent plaques with a “hairy” texture. In 60% of these patients the lesions were bilateral; in 1 patient lesions covered the dorsal surface of the tongue; and in 1 patient lesions were found on the buccal mucosa. Coexisting skin diseases were frequent and included oral candidiasis (71% of patients), seborrheic dermatitis (55%), folliculitis (34%), Kaposi’s sarcoma (27%), and herpes zoster (21%). Most patients had significant immunosuppression at the time of diagnosis of oral hairy leukoplakia; 75% had CD4+ T lymphocyte counts less than 354/µL, and more than 50% had already had an AIDS-defining opportunistic infection diagnosed. The entire group of patients with HIV infection and the subgroup of HIV patients with oral hairy leukoplakia were stratified according to their CD4+ T lymphocyte count at diagnosis. For all patients who had CD4+ T lymphocyte counts of 300/µL or more at diagnosis, HIV patients with oral hairy leukoplakia had a significantly shorter median survival time (25 months) than the group as a whole (52 months).

Conclusions.—Patients with HIV typically have advanced disease by the time their oral hairy leukoplakia is diagnosed. Other investigators have demonstrated that oral hairy leukoplakia is a marker of progression to AIDS. In this study, the only prognostic significance of oral hairy leukoplakia was in patients whose CD4 + T lymphocyte counts were 300/µL or more at diagnosis; these patients had half the estimated survival time as patients with HIV but without oral hairy leukoplakia. The lesions of oral hairy leukoplakia were well characterized clinically and almost always appeared on the lateral tongue.

 The finding of oral hairy leukoplakia in patients with HIV infection indicates advanced immunosuppression. Even in patients with relatively high CD4 T lymphocyte counts, oral hairy leukoplakia is associated with a poor prognosis.

In Situ Polymerase Chain Reaction-based Localization Studies Support Role of Human Herpesvirus-8 as the Cause of Two AIDS-related Neo¬plasms: Kaposi’s Sarcoma and Body Cavity Lymphoma

Introduction.—It has been suggested that human herpesvirus 8 (HHV- 8), a new herpesvirus, may be the cause of Kaposi’s sarcoma (KS) and body cavity B-cell lymphoma in patients with AIDS. If HHV-8 is the cause of these 2 AIDS-associated tumors, it should be detectable in the earliest clinical lesions. It also should localize to specific target cells in a pattern that reflects the tumorigenic pathways. The localization of HHV-8 in early patch stage KS lesions is reported.

Methods.—The study analyzed 21 biopsy specimens of patch stage KS lesions. In situ polymerase chain reaction (PCR) was performed, with and without simultaneous immunostaining. Normal skin from healthy subjects was studied as well.

Results.—None of the control specimens showed any HHV-8 DNA by either PCR or in situ PCR. All PCR-positive specimens showed distinct, specific in situ PCR staining. In 4 patch stage KS lesions, in situ PCR staining localized to nuclei of endothelial cells and perivascular spindleshaped tumor cells. Later stage KS lesions, that is, plaques and nodules, showed further positive cells, including epidermal keratinocytes and eccrine epithelia. Specific HHV-8 infection of endothelial cells, KS tumor cells, and epithelioid pneumocytes also were detected in pulmonary KS. Dual staining of body cavity B-cell lymphoma showed HHV-8 in malignant tumor cells but not in reactive lymphocytes.

Conclusions.—The findings show temporal and spatial associations between HHV-8 and the AIDS-related neoplasms KS and body cavity B-cell lymphoma. More definitive studies are needed to determine how widespread HHV-8 is in the population, and whether it is the true cause of KS.

 These authors report that HHV-8 can be found in early patch stage lesions of KS, where they are localized to endothelial cells and spindle-shaped tumor cells. In advanced lesions, the virus can be found in other cells as well. Similarly, in body cavity-based B-cell lymphoma, HHV-8 is present in malignant tumor cells and not in reactive lymphocytes. These findings support a causal role for HHV-8 in the pathogenesis of these 2 AIDS-related conditions.

AIDS-related Kaposi’s Sarcoma: Prospective Validation of the AIDS Clinical Trials Group Staging Classification

Introduction.—Cancer staging systems were designed for the planning and evaluation of treatment and as indicators of prognosis. Unique challenges are presented in staging Kaposi’s sarcoma in persons infected with HIV type 1 (HIV-1). A proposed staging system for AIDS-related Kaposi’s sarcoma was developed in 1988 that classified patients into poor-risk or good-risk groups on the basis of tumor extent and immune system status. To validate this system, staging and survival data were collected on patients enrolled in clinical trials for Kaposi’s sarcoma sponsored by the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. An analysis of this system and potential refinements are presented.

Methods.—In 294 patients, AIDS-associated Kaposi’s sarcoma was staged according to tumor extent, severity of immunosuppression, and other systemic HIV-1-associated illnesses. These patients were observed for survival. For each variable according to published criteria by the AIDS Clinical Trials Group, the patients were classified as at good risk or poor risk. To evaluate the association between the variables and survival, univariate and multivariate analyses were performed. To improve the predictive value of the staging system, additional analyses were conducted.

Results.—For each of the variables, survival was significantly shorter for patients in the poor-risk category. For patients in the good-risk category of tumor extent, median survival was 27 months, and in patients in the poor-risk category it was 15 months. For severity of immunosuppression, patients in the good-risk category had a median survival of 40 months and those in the poor-risk category had a median survival of 13 months. For other systemic HIV-1-associated illnesses, patients in the good-risk category had a median survival of 22 months, and those in the poor-risk category had a median survival of 16 months. The most predictive information was severity of immunosuppression. Significant additional predictive information in patients whose immune function was least impaired was provided by tumor extent. A simplified model resulted by using a CD4 count of 150/µL rather than 200/µL.

Conclusion.—In patients with AIDS-related Kaposi’s sarcoma, survival can be predicted with this classification system. The most predictive information was found with CD4 count and tumor stage. Better discrimination between prognostic groups was found by using a lower CD4 count than originally proposed.

 In patients with relatively high CD4 counts, tumor extent added significant prognostic information. This provides a strong rationale for the treatment of early Kaposi’s sarcoma in these individuals. The staging system presented here may be further refined by inclusion of other variables that may more accurately reflect Kaposi’s sarcoma or HIV-1 biology, such as viral load, markers of immune activation, or more specific poor-risk tumor features.