Therapeutic application of zinc in human immunodeficiency virus against opportunistic infections.

The relevance of zinc in resistance to infections by virus, fungi and bacteria is recognized because of its pivotal role in the efficiency of the entire immune system, in particular in conferring biological activity to a thymic hormone called thymulin, which has differentiation properties on T-cell lines. In infection with human immunodeficiency virus (HIV), the zinc-bound form of thymulin (active thymulin, ZnFTS) is strongly reduced in stage IV of the disease (Centers for Disease Control and Prevention classification) with concomitant decrements in CD4(+) cell count and zincemia values. The zinc-unbound form of thymulin (inactive thymulin, FTS) is, in contrast, very high. The in vitro addition of zinc to plasma samples induces a recovery of the thymulin active form, suggesting low zinc bioavailability as the cause of impaired thymic functions with consequent CD4(+) depletion. An analysis of risk factors for the incidence of recidivism opportunistic infections shows CD4(+) depletion and zinc deficiency to have significant scores. Supplementation with zinc for 1 mo (45 mg Zn(2+)/d) associated with zidovudine (AZT) therapy in stage IV induces recovery of active zinc-bound thymulin, of zincemia, of CD4(+) cells with concomitant reduction (50%) of recidivism opportunistic infections compared with the AZT-treated group. Complete disappearance of recidivism by Candida aesophagea or Pneumocystis carinii is observed after supplementation with zinc. The relative risk factors (CD4(+) depletion and zinc-deficiency) have lower scores in the HIV-positive zinc-treated group, confirming, as such, the relevance of zinc in opportunistic infections that involve extracellular matrix. Such an assumption is indirectly confirmed with new HAART, where no opportunistic infections occur. Indeed, HIV RNA is inversely correlated with both CD4(+) and zincemia values (r = -0.73, P<0.01) in HAART-treated subjects. Lower scores for the same relative factors for the appearance of opportunistic infections are present in HAART-treated subjects compared with those treated with AZT. These findings, on the one hand, show the poor efficacy of AZT therapy compared with HAART therapy for the progression of HIV, but on the other hand, they suggest that the lack of occurrence of opportunistic infections by HAART may also result from major zinc bioavailability. This further supports the key role played by zinc against opportunistic infections in HIV with a possible independent effect by either HIV or the pathogens involved.

Nutrients and HIV: part one -- beta carotene and selenium.

Micronutrient deficiencies are common in HIV/AIDS, resulting from both malabsorption and virally-caused depletion. Beta carotene and selenium deficiencies, two of the most common nutrient deficiencies, are important due to their dual function as nutrients necessary for immune modulation and as antioxidants. Beta carotene deficiencies are common in all stages of HIV/AIDS and may signal malabsorption. Supplementation has been shown to affect specific T lymphocyte populations and decrease markers of lipoperoxides. Selenium levels are highly significant in predicting AIDS-related mortality; and the HIV virus manufactures selenoproteins that are involved in the regulation of viral replication, possibly depleting host levels of selenium. Supplementation trials with individual antioxidants have shown improvement in immunological parameters and decreased evidence of lipid peroxidation.

Antiviral update.

AIDS: Data collected from several studies can provide guidance on new therapies for treatment-experienced patients. A study comparing two different triple-drug combination therapies, both using Indinavir, showed no significant differences in antiviral activity. A study of a triple-drug regimen that included Delavirdine, produced more favorable results than two different dual combination regimens. A small study indicated that "recycling" previously used antiviral drugs with two new drugs into a 6-drug regimen had positive short-term effects as a salvage therapy. However, adherence to such a regimen may prove difficult. A larger study of another salvage therapy, which used Ritonavir plus Saquinavir plus two NARTIs, had different results depending on whether the patient had been treated previously with Ritonavir or with Saquinavir. Two other studies examined different dosages of Nelfinavir or Indinavir and found that twice-a-day dosing may be as effective as three times a day. More research is needed to supplement the available knowledge for treating patients who most need alternative therapies.^ieng

The impact of ethanol and Marinol/marijuana usage on HIV+/AIDS patients undergoing azidothymidine, azidothymidine/dideoxycytidine, or dideoxyinosine therapy.

Therapeutic observations suggest that azidothymidine (AZT)-resistant HIV+/AIDS patients are frequently offered AZT/dideoxycytidine (DDC) or dideoxyinosine (DDI) therapy. The latter therapies have been associated with the development of acute pancreatitis. During the initial portion of this study, when patients reported limiting ethanol consumption, an increase in CD4+, a decrease in amylase, and a decrease in lipase was observed in patients on DDI monotherapy. Marinol/marijuana usage was associated with depressed CD4+ counts and elevated amylase levels within the DDI subgroup. The purpose of this study was to follow these patients over 1 year and compare clinical indicators of pancreatitis and HIV progression. After 1 year, the remaining 56 patients were reexamined in the follow-up portion for clinical indicators of HIV disease progression and pancreatoxic/hepatotoxic effects. Those in the AZT group, who remained on this therapy throughout the year, had significantly increased amylase values from 55.3 to 69.3 IU/liter (p < 0.05). In the AZT/DDC group, those who remained on combination therapy throughout the year, 4 of the 5 clinical indicators of disease progression changed. Amylase, ALT, and AST all increased significantly from 55.2 to 77.8 IU/liter (p < 0.01), from 38.0 to 92.3 IU/liter (p < 0.05), and from 55.2 to 97.0 IU/liter (p < 0.05), respectively. Lipase levels decreased significantly (106.0 to 74.6 IU/liter, p < 0.05). The most remarkable changes occurred in the AZT/DDC group (who reduced ethanol consumption), wherein clinical indicators of pancreatitis and liver dysfunction declined, including amylase (65.0 to 20.0 IU/liter, p < 0.05), ALT (350.0 to 100.0 IU/liter, p < 0.01), and AST (240.0 to 95.0 IU/liter, p < 0.01). No significant changes were noted in the DDI or AZT groups. Marinol/marijuana use was associated with declining health status in both the AZT and AZT/DDC groups. In contrast, all clinical indicators of pancreatitis improved in the DDI patients who utilized Marinol/marijuana, including amylase (-34%), lipase (-30.8%), ALT (-21.4%), and AST (-20.1%). This paired follow-up study suggests that HIV+/AIDS patients on antiretroviral therapies should restrict their ethanol consumption. In HIV+/AIDS patients with the lowest CD4+ counts (those on DDI monotherapy), utilization of Marinol/marijuana does not seem to have a deleterious impact.

ICAAC update on opportunistic infections.

AIDS: Recent research on the effects of opportunistic infections (OIs) on HIV replication suggests that the OIs can actually increase HIV replication through the production of cytokines. Treatment options for thrush include antifungal treatments for early episodes and reserving fluconazole for patients with difficult to treat infections. Other studies show that prevention and treatment of Mycobacterium avium complex (MAC) increases survival rates. Drugs and dosages are described.^ieng

Case report: successful treatment with cimetidine and zinc sulphate in chronic mucocutaneous candidiasis.

The authors evaluated the clinical efficacy of a treatment with cimetidine and zinc sulphate in a patient with chronic mucocutaneous candidiasis. Cimetidine was given at a dose of 400 mg three times daily; zinc sulphate at a dose of 200 mg daily, then adjusted to maintain blood zinc levels at the upper normal range. This treatment lasted 16 months. An impressive and significant reduction of the infectious events and an increased CD4 (helper/inducer) cell counts were observed. The authors conclude that this combined immunopotentiating treatment is safe and inexpensive to treat immunodeficiency disorders.

Oral zinc supplementation in the treatment of HIV-infected children.

Primary zinc (Zn) deficiency has been reported to cause immune dysfunction; secondary Zn deficiency has been noted in HIV-infected adults; and in vitro studies have suggested that Zn may have antiviral activity. Zn supplementation was studied in HIV-infected children to evaluate selected clinical and laboratory responses. Thirteen clinically stable HIV-infected children (five females, eight males, 1.5-10 years of age, mean 6 years) with CD4+ counts < 500/mm3 were supplemented with oral elemental zinc at 1.8-2.2 mg/kg/day for 3 to 4 weeks. HIV p24 antigen (p24) levels, T-cell subsets, and serum Zn and copper (Cu) levels were measured before and at the end of Zn supplementation. Clinical assessment of appetite, sense of well being, weight change, and days of fever over 38 degrees C was performed at these times. Baseline serum Zn levels were abnormally low in nine (69%) HIV-infected children. After oral elemental Zn supplementation, six had increased their serum Zn level into the normal range. However, only two patients had increased CD4+T-cell numbers and none of the seven patients with positive p24 had decreased p24 levels. Clinical scores improved in only four patients. This study does not demonstrate impressive short-term benefit from oral Zn supplementation in HIV-infected children.

Clinical and lymphocyte responses to beta-carotene supplementation in 11 HIV-positive patients with chronic oral candidiasis.

Eleven HIV-positive patients with chronic oral candidiasis were supplemented with 60 to 120 mg of beta-carotene daily for 3 to 7 months. Lymphocyte profiles were evaluated at intervals to help assess immune competence. Although there was a modest increase in some lymphocyte values at 2 months, there was a significant decrease in numbers of CD4 and CD8 cells and CD4 percentage of lymphocytes after 6 months of beta-carotene supplementation. Serum triglyceride and liver enzyme levels were not affected by the beta-carotene supplementation. No improvement was observed in the control of the oral candidiasis. Under the conditions of the study, there was no indication that daily beta-carotene supplements enhanced immune competence or was of benefit in managing oral candidiasis.