Efficacy testing of recombinant human immunodeficiency virus (HIV) gp160 as a therapeutic vaccine in early-stage HIV-1-infected volunteers. rgp160 Phase II Vaccine Investigators.

A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4+ cell counts >400 cells/mm3. During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, followed by booster immunizations every 2 months. Repeated vaccination with rgp160 was safe and persistently immunogenic. Adequate follow-up and acquisition of endpoints allowed for definitive interpretation of the trial results. There was no evidence that rgp160 has efficacy as a therapeutic vaccine in early-stage HIV infection, as measured at primary endpoints (50% decline in CD4+ cell count or disease progression to Walter Reed stage 4, 5, or 6) or secondary endpoints. A transient improvement was seen in the secondary CD4 endpoint for the vaccination compared with the placebo arm, but this did not translate into improved clinical outcome.

Bacteremia in HIV-infected patients: short-term predictors of mortality.

To identify characteristics associated with mortality in HIV-infected patients with bacteremia, 88 bacteremic episodes in 80 HIV-infected patients were prospectively identified over a 5-month period and observed for 30 days. Demographic, clinical, laboratory, and radiologic data were collected. Mean and median age was 41 years. Most study subjects were homosexual men. Median CD4 count was 20 cells/mm3. Gram-positive organisms predominated (65%). The most common source of bacteremia was intravascular catheters (45%). Overall mortality was 30%. A history of malignancy, three or more opportunistic infections, shock, low hemoglobin, source of bacteremia other than an intravascular catheter, resistance to therapy, and a second bacteremic episode during the study period, were all found to be independent predictors of mortality. In this cohort of HIV-infected patients, most of whom were severely immunosuppressed, several factors were found to be significantly and independently associated with mortality.

Pneumocystis carinii pneumonia.

Throughout the epidemic, Pneumocystis carinii pneumonia (PCP) has been the most common AIDS-defining opportunistic infection in the United States. With the widespread use of highly active antiretroviral therapy (HAART) and prophylaxis in patients known to be at risk, the incidence of PCP in patients with AIDS has declined dramatically. However, it is still seen regularly in patients with previously undiagnosed human immunodeficiency virus (HIV) infection, those who do not comply with prophylactic medications, and in occasional cases of failure of prophylaxis. Despite many years of study, our understanding of the biology, ecology, and pathogenesis of PCP is inadequate. Clinically, PCP in AIDS tends to be a less acute and milder illness than PCP in other types of immunocompromised hosts. Although the radiograph typically shows bilateral diffuse granular opacities, many other patterns are seen. Trimethoprim-sulfamethoxazole is the preferred drug for treating and preventing PCP, but toxicity limits its use. The choice of treatment is influenced by the severity of illness and relative toxicities of antipneumocystis agents. Adjunctive corticosteroid therapy is recommended for patients with moderate or severe disease. The success of HAART has prompted investigators to question whether prophylaxis against PCP and other opportunistic infections is necessary in patients who respond with a rise in CD4 lymphocyte counts and suppression of HIV replication.

Vitamin A deficiency in non-vitamin-supplemented patients with AIDS: a cross-sectional study.

The prevalence of vitamin A deficiency and its association with dietary retinol intake in patients with AIDS was assessed in a cross-sectional study. Sixty eligible patients with AIDS provided serum samples that were analyzed for retinol content. Exclusion criteria included current use of vitamin supplements (57% of the 140 willing to participate) and pregnancy (none). Past dietary intake was determined using a standardized food intake frequency questionnaire. The prevalence of hyporetinemia was 22%. This was a 241-fold greater prevalence than that of a representative sample of the U.S. population, after adjusting for age and sex. There was a positive association between serum retinol status and dietary intake, but 27% of those with adequate intake had serum retinol levels below the normal range. These findings suggest that regardless of intake, patients with AIDS may represent a population at considerable risk of vitamin A deficiency.

Osteomyelitis caused by Mycobacterium haemophilum: successful therapy in two patients with AIDS.

OBJECTIVE: Difficulties involved in diagnosis and response to antimicrobial therapy are described in detail for two cases of biopsy-proven osteomyelitis caused by Mycobacterium haemophilum in AIDS patients. SETTING: Two large, private teaching hospitals in New York City, New York, USA. PATIENTS, PARTICIPANTS: A 31-year-old woman with previous diagnoses of candida esophagitis and peripheral neuropathy (patient 1), and a 37-year-old man with Kaposi's sarcoma (patient 2). INTERVENTIONS: One patient was treated with a combination of rifampin, ethambutol, clofazimine, and ciprofloxacin, while the other received rifampin, ciprofloxacin and doxycycline. Both patients also received a short course of intravenous amikacin. MAIN OUTCOME MEASURES: Disease activity was monitored clinically by observing resolution of skin ulcers, lymphadenopathy, and pain and swelling in areas affected by osteomyelitis. RESULTS: Both patients experienced complete resolution of signs and symptoms of M. haemophilum infection. Patient 1 was treated for 17 months and remains well after 10 months without therapy. Patient 2 shows no evidence of infection after 14 months of therapy. CONCLUSIONS: M. haemophilum infection must be considered in the differential diagnosis of osteomyelitis in AIDS patients, although specialized culture techniques are required to isolate and identify this pathogen. Excellent clinical response can be achieved with oral antimicrobial therapy.

The febrile father with a cytomegalovirus infection. A family affair.

Existing evidence has convincingly established that young children often transmit cytomegalovirus (CMV) infection to their parents. What proportion of these parental infections lead to clinical disease is unknown, but this sequence of events is probably not rare. Physicians seeing young adults with prolonged but otherwise nondescript febrile illness should inquire about the presence of young children in the household. Parental CMV infection is not limited to parents whose children attend day-care centers or are cared for in neonatal intensive care units. As in our case of the febrile father, it may be strictly a family affair.

Lack of effect of oral acyclovir on prevention of aphthous stomatitis.

Aphthous stomatitis (canker sores) is a common cause of recurrent mouth ulceration. The effect of long-term oral acyclovir therapy on aphthous stomatitis recurrences was evaluated in 44 patients who were in a double-blind treatment trial for recurrent genital Herpes simplex infections. Twenty-five subjects received oral acyclovir daily for one year, while 19 received the drug only during outbreaks of herpes. The number of patients who experienced recurrences of aphthous stomatitis and the frequency and duration of attacks per patient were not significantly different between groups. Furthermore, no consistent change in attack rate was observed in members of either group compared to that reported before they had entered the trial. We conclude that oral acyclovir is not effective for prevention of recurrent aphthous stomatitis in most patients.

Spinal cord syndromes in the acquired immune deficiency syndrome.

Two patients with AIDS developed paraparesis. Neuropathological post mortem examination in one revealed cytomegalovirus polyradiculopathy, and in the second, vacuolar myelopathy which occurred in association with brain lesions resembling Marchiafava-Bignami Syndrome.

Sequential disseminated tuberculosis and toxoplasmosis in a Haitian refugee.

A 27-year-old previously healthy male Haitian had sequential disseminated tuberculosis and toxoplasmosis during a three-month period. The former appeared to respond to antituberculous therapy; the latter proved fatal and was diagnosed only at autopsy. We suspect acquired immune deficiency syndrome (AIDS) as the underlying problem, which emphasizes the danger of sequential unusual infections in patients from groups with a high incidence of AIDS. This case also illustrates some of the difficulties of diagnosing toxoplasmosis and the advisability of early empiric therapy in such patients.

Transfusion malaria: treatment with exchange transfusion after delayed diagnosis.

A 65-year-old woman was rehospitalized for increasing mental confusion 16 days after open heart surgery for mitral stenosis. A diagnosis of transfusion-acquired falciparum malaria was made from a routine peripheral blood smear 24 hours after admission. Because progressive encephalopathy developed while she was receiving antimalarial drugs, a therapeutic exchange transfusion was performed. Clinical improvement occurred promptly during the exchange, and the patient went on to complete recovery from her malaria. The putative blood donor involved met the currently accepted standards for blood donors.

Association of hepatitis B virus infection with hepatocellular carcinoma in American patients.

Thirty-four patients from the Philadelphia area with hepatocellular carcinoma (HCC) were matched with colon cancer patients, lung cancer patients and blood donors according to age and sex. Sera from the four groups were tested to determine the prevalence of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc). Five of the HCC patients (14.7%) and none of the controls were positive for HBsAg. At least one of the three serologic markers of hepatitis B virus (HBV) infection was found in 51.5% of the HCC patients, 5.3% of the colon cancer patients, 11.1% of the lung cancer patients, and 10.7% of the blood donors. Twelve of the seventeen seropositive HCC patients (70.6%) were positive for anti-HBc alone, while all of the seropositive lung cancer patients and donors were positive for anti-HBs alone. Sera positive for any HBV marker were also tested for e antigen (HBeAg) and its antibody (anti-HBe). Four of the HCC patients (23.5% of the seropositives) had anti-HBe, while none of the sera tested had HBeAg. A history of alcoholism did not appear to influence HBV seropositivity in the HCC patients. This study supports the hypothesis that HBV infection is closely associated with HCC even in areas where both conditions are uncommon. The wide disparity between seropositivity for HBsAg and anti-HBc in the HCC patients is an unusual feature, for which an age effect may be the best explanation.