International Association of Physicians in AIDS Care, January 2000 Journal
David S. MacDougall
| TB: Paradoxical Responses Non-PI Regimens Opportunistic Infections |
In the midst of a growing wave of riots, protests, and other forms of rebellion, a group of delegates from twelve of the thirteen original colonies (Georgia was absent) met in Philadelphia's Carpenter's Hall in 1774 at the First Continental Congress to discuss how to return to a state of harmonious relations with the Mother Country. Revolution was not the agenda at this initial meeting, but radical thinking eventually won out. Parliamentary taxes were declared invalid, an import-export ban was established, and Colonists were urged to arm themselves for the inevitable conflict to come.
More than 200 years later, nearly 8,000 delegates from around the world met in the City of Brotherly Love not to fan the flames of revolution but to explore new approaches to the diagnosis and treatment of infectious diseases. The 37th annual meeting of the Infectious Diseases Society of America was held November 18-21, 1999, within earshot of the site of the birth of the American Revolution. The enemy this time was not the British Crown but microbial pathogens, and the weapons of choice were not muskets and cannons but drugs and vaccines. The overriding message of the conference, however, was similar to that spread by the Founding Fathers in 1774, that is, be prepared for the battles to come.
One of the primary battles to be fought will be that of coinfection with hepatitis C virus (HCV) in persons with HIV infection. "As survival among HIV-infected persons increases due to the use of highly active antiretroviral therapies and the prophylaxis of opportunistic pathogens, HCV-related disease will become an increasingly important cause of morbidity and mortality among HIV-infected persons," said Mark Sulkowski, MD, Johns Hopkins University, Baltimore, Maryland. According to Sulkowski, about 30 percent of the estimated 1 million persons in the United States with HIV infection are coinfected with HCV.
Because HCV infection is readily acquired by parenteral exposure, he said, about 90 percent of those who acquire HIV by intravenous drug use (IVDU) are also HCV-infected. In contrast, about 10 percent of those who acquire HIV by sexual exposure are coinfected with HCV. About 2 percent of the general US population is infected with HCV. The growing threat of HCV infection in persons with HIV infection was documented in a poster presentation by Arvind Gupta, MD, and colleagues, Lehigh Valley Hospital, Allentown, Pennsylvania. The frequency of HCV infection in patients with a new diagnosis of HIV infection at their institution increased from 7.3 percent to 49 percent during the two-year period between the first six months of 1996 and the first six months of 1998. The researchers noted that about 30,000 new cases of acute HCV infection are estimated to occur each year in the United States, only about 25 percent of which are diagnosed.
Sulkowski said that the effects of HCV infection on the natural history of HIV infection are different from those of HIV infection on concurrent HCV infection. HCV infection does not appear to alter the natural history of HIV infection in patients with normal liver function, Sulkowski said, although HIV disease progression is significantly increased in persons with concurrent HCV infection and advanced liver disease. In persons with HCV infection, HIV seroconversion is associated with increased HCV RNA levels and a 3-fold increased risk of vertical HCV transmission.
HIV infection significantly alters the natural history of HCV infection, Sulkowski said. Advanced liver disease is significantly more common in persons with HIV/HCV coinfection than in those with HCV infection alone, and the rate of progression to cirrhosis is significantly increased in HIV/HCV coinfected patients. In persons with HCV infection, independent variables associated with progressive liver disease include HIV infection, CD4 cell count, alcohol consumption, and age at infection.
The effects of HIV infection on the clinical outcomes of HCV infection are predictable, Sulkowski said. In persons with HIV/HCV coinfection, the risk of end-stage liver disease (ESLD) is increased about 90-fold as compared with the general population. In persons with HCV infection, the rates of ESLD and hepatic carcinoma are increased about 16-fold and 6-fold, respectively, as compared with the general population.
HAART-associated immune reconstitution has no significant effect on HCV RNA levels, Sulkowski said, although progression of liver fibrosis may be decreased in persons with HCV infection receiving HIV protease inhibitors (PIs). The risk of severe hepatotoxicity is significantly increased in HIV/HCV coinfected patients treated with ritonavir, he said, but not in those receiving other PIs or HIV reverse transcriptase inhibitors. About 10 percent of HIV/HCV coinfected patients receiving HAART develop hepatotoxicity, Sulkowski said.
According to guidelines recently released by the US Public Health Service, all persons with HIV infection should be screened for HCV and hepatitis A virus (HAV) infection. All HIV-positive patients with HCV infection should be advised to avoid alcohol consumption, Sulkowski said, and those who are HAV IgG-negative should receive HAV immunization.
The treatment of HCV infection in persons with HIV infection is problematic, Sulkowski said, and the first challenge is deciding who to treat. According to Sulkowski, patients with stable HIV disease and concurrent HCV infection can probably be treated like HIV-negative patients with HCV infection. "The goal of treatment in these individuals is to eradicate HCV, as in those who are HIV-negative," he said.
Patients with HIV/HCV coinfection and advanced liver disease may require a different approach. "The goal of treatment in these patients is to delay progression of liver dysfunction," Sulkowski said. Persons with HIV/HCV coinfection and advanced liver disease are poor candidates for liver transplantation, he said, and such patients may benefit from aggressive anti-HCV interventions.
Patients with HIV/HCV coinfection may be at increased risk of HAART- associated hepatotoxicity, and this risk may compromise anti-HIV therapy. "There is some anecdotal evidence that treatment of HCV infection may permit more aggressive treatment of HIV infection," Sulkowski said. "In all patients, however, HIV disease remains the priority."
The second challenge in the management of HIV/HCV coinfected patients is deciding how to treat. Only about 15 percent of HIV/HCV coinfected patients achieve a sustained response to a standard course of interferon (INF) monotherapy (5 MU three times weekly for 24 weeks), Sulkowski said. CD4 count >500 cells/mm3 is one of the primary predictors of response to INF monotherapy in patients with HIV/HCV coinfection.
Experience with the combination of INF and ribavirin (RBV) in HIV/HCV coinfected patients is limited, Sulkowski said. One of the main drawbacks of INF/RBV treatment in HIV/HCV coinfected patients is that RBV is associated with dose-dependent hemolytic anemia. A second area of concern is that of drug-drug interactions. Like the pyramidine nucleoside analogues ZDV, d4T, and ddC, RBV requires phosphorylation to a triphosphate to become active within cells. RBV is antagonistic with the pyramidine nucleoside analogues and synergistic with ddI, according to Sulkowski.
Sulkowski described the preliminary findings of a prospective study of INF/RBV combination therapy in patients with HIV/HCV coinfection. In this study, 27 patients with HIV/HCV coinfection were randomized to receive INF monotherapy or INF/RBV combination treatment for 12 weeks. Early virologic response, defined as undetectable HCV RNA at treatment week 12, was achieved by 9 percent of patients in the INF monotherapy group and 50 percent of those in the INF/RBV combination group (p = 0.04). The mean decrease in HCV viral load at week 12 was 0.85 and 3.2 log10 copies/ml in the INF and combination treatment groups, respectively (p = 0.02). HIV RNA levels and CD4 cell counts remained stable in both groups during treatment. Treatment was discontinued because of adverse effects in two patients in the INF group and seven patients in the INF/RBV group.
Several posters presented at the conference examined the demographic and epidemiologic characteristics of HIV/ HCV coinfection in urban and rural settings. The seroprevalence of HCV infection was determined in a group of 248 patients attending an urban HIV outpatient clinic in a study by John Bardugon, MD, and colleagues, Louisiana State University Health Science Center, New Orleans. In the 248 patients, 23.4 percent had antibodies to HCV. Factors associated with HCV infection on multivariate analysis were older age and history of IVDU and/or incarceration.
The prevalence of HCV infection may be similar in both rural and urban populations with HIV infection. In a study by Catherine Sallenave-Karpman, MD, and colleagues, University of Vermont College of Medicine, Burlington, HCV seroprevalence was determined in 161 rural patients with HIV infection. HCV serology was positive in 32.3 percent of the patients. Those with and without HCV infection were similar in terms of age, gender, and CD4 cell count. IVDU was a risk factor for HIV infection in 75.7 percent and 6.8 percent of the HCV-positive and HCV-negative patients, respectively.
The effects of HCV coinfection and the hepatotoxicity of antiretroviral drugs in persons with HIV infection may be reflected in increasing hepatic morbidity and mortality in this population. "End-stage liver disease is now the leading cause of death among HIV-positive patients at our institution," said Barbara McGovern, MD, Tufts University School of Medicine, Boston Massachusetts. McGovern's statement was based on a retrospective study of 22 HIV-positive patients who died in 1998-1999 and 27 similar patients who died in 1991. Death was a direct result of complications secondary to end-stage liver disease in 50 percent of the patients in the 1998-99 cohort and 15 percent of those in the 1991 cohort (p <0.01). Both groups were similar in terms of serologic markers of HCV and hepatitis B virus (HBV) infection. Deaths in the remaining patients in both cohorts were related to bacterial infections, malignancies, and opportunistic infections. McGovern noted that 32 percent of the patients in the 1998-99 cohort discontinued antiretroviral therapy because of abnormal liver function tests.
Despite the proven efficacy of DOTS (directly-observed treatment, short-course) in the treatment of Mycobacterium tuberculosis (TB) infection, only 16 percent of all estimated TB cases reported worldwide in 1998 were treated under DOTS, said Mario Raviglione, MD, World Health Organization (WHO), Geneva, Switzerland. Speaking at a workshop session, Raviglione said that current WHO surveillance data reveals that the total number of countries using DOTS increased from 10 in 1993 to 110 in 1998, although the implementation of DOTS in some high-burden countries has been slow. Among the 22 top-burden countries, Vietnam and Peru have had the most successful DOTS implementation programs, while little progress has been seen in larger countries including India, the Philippines, Indonesia, Russia, and Nigeria. About 3.4 million TB cases were reported worldwide in 1997, and the overall TB case detection rate worldwide is about 30 percent.
The primary reason for the slow expansion of effective TB control programs in some regions is a lack of political will and commitment by government and other institutions, Raviglione said. The TB cure rate is about 80 percent in countries using DOTS as compared with about 40 percent in non-DOTS countries. TB continues to represent a major public health burden worldwide (Table 1), Raviglione said, and the problem is compounded by the spread of the HIV epidemic and the emergence and spread of multidrug-resistant TB (MDR-TB).
Source: Mario Raviglione, MD |
According to Raviglione, more than 10 million persons worldwide are coinfected with TB and HIV, of whom 70 percent live in sub-Saharan Africa. Persons with TB/HIV coinfection are at increased risk of infection with MDR-TB and reactivation of latent TB infection, he said.
Newly-revised but unpublished recommendations for the treatment of latent TB infection, sponsored by the American Thoracic Society and other organizations, were described by David Cohn, MD, Department of Public Health, Denver, Colorado. According to Cohn, the rationale for the new recommendations is based on recent data demonstrating the limitations of 6-12 months of treatment with isoniazid and the efficacy of short-course rifampin-containing regimens in HIV-infected patients. The recommendations are also bolstered by widespread recognition that increased treatment of latent TB infection, like increased TB case detection and cure rates, is pivotal to the eventual elimination of TB, Cohn said.
The risk of active TB is increased in patients with diabetes, gastrectomy, renal failure, solid organ transplantation, and other clinical conditions, Cohn said. Among those who are tuberculin skin test-positive, HIV/AIDS is the greatest risk factor for the development of active TB. Other tuberculin-positive persons at increased risk of active TB are those with recent TB infection, silicosis, and those with radiographic findings consistent with old TB.
A summary of the revised recommendations for the treatment of latent TB infection in persons with and without HIV infection is provided in Table 2. Changes in recommendations for clinical and laboratory monitoring include the elimination of routine baseline and follow-up monitoring in most persons with latent TB infection except those with HIV infection, pregnant or postpartum women, and those with a history or increased risk of liver disease. Cohn said that the complete recommendations will be published by the US Centers for Disease Control and Prevention in the spring of 2000.
Source: David L. Cohn, MD |
Patients with TB infection may develop worsening of TB symptomatology and lesions soon after the initiation of anti-TB therapy. These "paradoxical responses," characterized by recurrent fevers and the development or worsening of pulmonary infiltrates or lymphadenopathy, frequently arouse suspicion of uncontrolled TB due to drug resistance and/or noncompliance.
Paradoxical responses have been recognized previously in seriously ill patients following the start of effective anti-TB chemotherapy and were believed to represent an enhanced anti-TB immune response. According to David Ashkin, MD, University of Miami School of Medicine, Florida, paradoxical responses may be observed with increased frequency following the initiation of antiretroviral therapy in persons with TB/HIV coinfection.
Ashkin described the findings of a study of the frequency and characteristics of this phenomenon in 33 patients with TB/HIV infection receiving combination antiretroviral therapy (Group 1), 55 patients with TB receiving anti-TB treatment (Group 2), and 28 patients with TB/HIV coinfection who were not receiving antiretroviral therapy (historical controls). Paradoxical response was defined as new persistent fever which developed after the initiation of antiretroviral therapy and which lasted for more than one week without an identifiable source combined with marked worsening or emergence of intrathoracic lymphadenopathy, pulmonary infiltrates, cervical adenopathy, or other tuberculous lesions.
The proportions of patients with paradoxical responses were 36 percent, 2 percent, and 7 percent in Groups 1, 2, and 3, respectively (Group 1 vs. Group 2, p <0.001, or Group 3, p = 0.013. Group 2 vs. Group 3, p = NS). Among patients in Group 1 who experienced a paradoxical response, the onset was significantly closer to the initiation of combination antiretroviral therapy (mean, 15 days) than to the initiation of anti-TB therapy (mean, 109 days) (p <0.001).
The most common symptoms in patients with paradoxical responses were hectic fevers, intrathoracic lymphadenopathy with worsening infiltrates, cervical lymphadenopathy, pleural effusions, appearance of miliary infiltrates, peritoneal TB, and worsening of cutaneous TB. Several patients with severe paradoxical responses required treatment with systemic steroids, and the most common indication for steroid treatment was painful exacerbations of cutaneous tuberculous lesions.
Patients with and without paradoxical responses were similar in terms of age, baseline CD4 cell counts and HIV RNA levels, and changes in CD4 cell counts and HIV RNA levels following the initiation of antiretroviral therapy. Of the patients with TB/HIV coinfection and paradoxical responses who were tested for delayed-type hypersensitivity reactions at baseline, 86 percent were anergic on admission but most of these patients had TB skin test conversion after the initiation of antiretroviral therapy. "It may be important to repeat tuberculin skin testing in HIV-infected patients following the initiation of highly active antiretroviral therapy," Ashkin said.
A variety of potential mechanisms may contribute to the appearance of paradoxical responses following the initiation of antiretroviral therapy in TB/HIV coinfected patients, Ashkin said. Paradoxical responses may be a reaction to persistent TB antigens in patients with ineffective clearance mechanisms, he said. In patients with HIV-related immunodeficiency, immune reconstitution following initiation of HAART may be associated with enhanced T-cell function and activation of cellular immunity with inflammatory responses including release of interleukins, tumor necrosis factor (TNF), and other cytokines. Such responses may be particularly frequent in patients with TB/HIV coinfection and increased HIV RNA levels at baseline who experience a significant decrease in viral load following the initiation of HAART, Ashkin said.
Patients with HIV infection who achieve prolonged suppression of viral replication during treatment with PI-based combination therapy may opt to switch to non-PI containing regimens because of adverse reactions, concerns about metabolic and other long-term effects of PIs, and the desire for a simpler dosing regimen. Several studies presented at the conference provided support for this strategy and for the use of non-PI regimens as initial therapy in treatment-naive patients with HIV infection.
Treatment with efavirenz (EFV) with or without abacavir (ABV) and one or two additional nucleoside reverse transcriptase inhibitors (RTI) is safe and effective in patients with HIV infection whose viral load is well-controlled on a PI-based regimen, and who do not have a history of prior antiretroviral treatment failure, said Malte Schutz, MD, Illinois Masonic Medical Center, Chicago. The finding emerged in a study of 34 patients with HIV infection and viral load <400 copies/ml on PI-based combination therapy who were switched to one of three non-PI regimens: EFV with two nucleoside analogues (Regimen 1); EFV and ABV with two other nucleosides (Regimen 2), or; ABV with two other nucleosides (Regimen 3).
All patients switched to Regimen 1, 88 percent of those switched to Regimen 2, and 50 percent of those switched to Regimen 3 had HIV RNA <50 copies/ml at study week 36. Of the four patients switched to Regimen 3 who experienced an increase in viral load, three had viral load <50 copies/ml at the time of treatment switch. Schutz said that the findings raise questions concerning the potency of ABV-containing regimens in patients treated successfully with PI-based regimens.
The combination of ABV, 3TC, and ZDV provided a potent and durable virologic response in treatment-naive patients with HIV infection in a study by Charles Hicks, MD, and colleagues, Duke University Medical Center, Durham, North Carolina. The study group included 246 treatment-naive patients with HIV infection who were randomized to receive ABV/3TC/ZDV or 3TC/ZDV. All patients randomized to 3TC/ZDV had the option of switching to ABV/3TC/ZDV at week 16.
At week 48, HIV RNA levels were <400 copies/ml in 60 percent of patients randomized to ABV/3TC/ZDV and 6 percent of those treated with 3TC/ZDV. Of the patients who added ABV after 16 weeks of treatment with 3TC/ZDV, 63 percent achieved HIV RNA levels <400 copies/ml at week 48. Median increases in CD4 cell counts at week 48 were similar in all patients.
Switching from a PI-based induction regimen to a non-PI maintenance regimen is associated with long-term viral suppression in selected adherent patients, reported W. Woodward and colleagues, Bornemann Internal Medicine, Reading, Pennsylvania. A group of 21 patients with HIV infection, viral load <50 copies/ml, and significant PI-related adverse effects, metabolic complications, or pill fatigue were switched to a non-PI regimen containing at least two nucleosides and one nonnucleoside RTI. All patients received extensive counseling about therapeutic options including treatment discontinuation prior to switching.
After at least 42 weeks of non-PI antiretroviral therapy, 15 patients (71 percent) maintained viral load <50 copies/ml. The remaining patients had viral rebound due to noncompliance or discontinued non-PI therapy due to drug reactions or hepatic failure. None of the patients discontinued non-PI therapy because of adverse medication effects. The average pill burden declined from 14.6 to 6.4 pills/day following the switch to non-PI treatment.
The combination of EFV, zidovudine (ZDV), and lamivudine (3TC) is superior to the combination of indinavir (IDV), ZDV, and 3TC in providing long-term suppression of HIV replication in patients without previous treatment with PI, 3TC, or nonnucleoside RTI, said Karen Tashima, MD, Miriam Hospital, Providence, Rhode Island. In an open-label, multicenter study, 1,266 patients with HIV infection were randomized to one of three treatment regimens: EFV (600 mg qd) + ZDV (300 mg bid) + 3TC (150 mg bid) (Group 1); IDV (800 mg q8h) + ZDV (300 mg bid) + 3TC (150 mg bid) (Group 2), or; EFV (600 mg qd) + IDV (1000 mg q8h) (Group 3). All patients had HIV RNA levels >10,000 copies/ml and CD4 counts >50 cells/mm3 at baseline.
At 72 weeks, HIV RNA levels and CD4 cell counts were similar in Groups 2 and 3. The proportions of patients with HIV RNA levels <400 copies/ml and <50 copies/ml at 72 weeks were significantly greater in Group 1 (67 percent and 60 percent, respectively) than in Group 2 (41 percent and 40 percent, respectively). The overall duration of response and time to treatment failure were significantly greater in Group 1 than in Group 2. Fewer patients in Group 1 than in Group 2 discontinued treatment because of adverse effects.
The nonnucleoside RTI emivirine (EMV) is safe and effective when used in combination with 3TC and stavudine (d4T) in treatment-naive patients with HIV infection, said D. Sereni, MD, and colleagues, Hopital Saint Louis, Paris, France. The conclusion was based on a study of 162 treatment-naive patients with HIV infection who were randomized to receive EMV/d4T/3TC or d4T/3TC for 48 weeks.
At week 24, the proportion of patients with HIV RNA levels <400 copies/ml was 83 percent in the EMV/d4T/3TC group and 40 percent in the d4T/3TC group. The adverse events observed with a frequency of 10 percent or greater were nausea, headache, dizziness, and rash. The combination of EMV/d4T/3TC was generally well tolerated and most adverse events were mild to moderate and occurred early in the course of therapy.
Interleukin-10 (IL-10) inhibits the production of IL-1, TNF, and other pro-inflammatory cytokines that are over-expressed in patients with HIV infection. IL-10 has been shown to inhibit HIV replication in various experimental systems but may upregulate HIV replication in chronically infected cells.
The effects of a short course of IL-10 therapy in patients with HIV infection were described by Jonathan Angel, MD, Ottawa General Hospital, Ontario, Canada. The study group included 39 patients with HIV infection on stable antiretroviral therapy. All patients received recombinant human IL-10 by subcutaneous injection in doses of 1 or 4 mcg/kg daily or 8 mcg/kg three times weekly for 22 days.
No significant change in HIV RNA levels or CD4 cell counts were observed in any of the groups. Treatment with IL-10 was generally well tolerated, although several patients discontinued treatment due to thrombocytopenia. Angel said that the findings from this limited study do not exclude potential immunological benefits of IL-10 in patients with HIV infection, and that effects of administration of IL-10 by different dosing regimens, for longer periods, or in different patient populations remain to be determined.
The much-heralded decreases in hospitalization rates for HIV-related pneumonias since the dawn of the HAART era are being offset by increasing rates of hospitalization for HIV-related malignancies, drug-resistant fungal infections, and other opportunistic infections (OIs), said Simon Paul, MD, Memorial Sloan-Kettering Cancer Center, New York City.
The finding emerged in a study of HIV-related hospital admissions at New York Presbyterian Hospital-Cornell Medical Center between 1995 and the first six months of 1999. From 1995 to 1997, the number of outpatients receiving care for HIV infection increased from 900 to 1,500 while the incidence of HIV-related hospital admissions decreased from 83 to 48 per 100 person-years. The incidence of bacterial pneumonia, the most frequent diagnosis throughout the study, decreased from 14 to 5.4 per 100 person-years between 1995 and 1999 while the incidence of Pneumocystis carinii pneumonia (PCP) decreased from 9.6 to 2.0 per 100 person-years. During the last two study years, the decreases in bacterial pneumonia, PCP, and other OIs were offset by increases in a range of other diagnoses including malignancies (from 1.5 to 4.0 per 100 person-years) azole-resistant candida infections, and herpes zoster. No further decreases in HIV-related hospitalization occurred between 1997 and 1999. HIV-related hospitalization rates for minorities, women, and IVDU increased between 1997 and 1999.
Infection with Streptococcus pneumoniae remains the most common cause of bacterial pneumonia in persons with HIV infection. All persons with HIV infection should receive pneumococcal vaccine soon after seroconversion, said Mark Dworkin, MD, US Centers for Disease Control and Prevention, Atlanta, Georgia.
The recommendation was based on an analysis of data from the Adult/Adolescent Spectrum of HIV Disease Project, an epidemiologic study of persons with HIV infection from over 100 inpatient and outpatient facilities in 11 US cities treated between January 1990 and December 1998. Of 39,086 patients with 71,116 person-years of follow-up, 585 episodes of pneumococcal disease were diagnosed (incidence, 8.2 per 1,000 person-years). Factors associated with a significantly increased risk for pneumococcal disease included IVDU, blood transfusion, African-American ethnicity, history of AIDS, decreased CD4 cell count, and alcoholism. Factors associated with a decreased risk of pneumococcal disease included recent prescription of clarithromycin or azithromycin prophylaxis and prescription of antiretroviral therapy. Immunization with pneumococcal vaccine provided significant protection against pneumococcal disease in patients with CD4 counts >500 cells/mm3 but not in those with lower CD4 cell counts.
Early initiation of systemic corticosteroids is associated with significant improvements in clinical course and decreased mortality in persons with HIV infection and suspected PCP, said Sridevi Kolla, MD, and colleagues, Episcopal Hospital, Philadelphia, Pennsylvania. The effects of early (<24 hours) and late (>24 hours) initiation of steroids were examined in 63 patients with HIV infection and suspected PCP. PCP was documented in 30 percent of the patients, and the remaining patients had other diagnoses established (17 percent) or no definite diagnosis (53 percent).
Improvement in clinical course was observed in 76 percent of those in the early steroid group and 50 percent of those in the late steroid group (p <0.05). Respiratory failure developed in 7 percent of those in the early steroid group and 40 percent of those in the late steroid group (p <0.05). Mortality was 17 percent and 10 percent in the early and late steroid groups, respectively.
Male-male sexual activity (MM) and blood transfusions as risk factors for HIV infection are associated with an increased risk of Clostridium difficile-associated diarrhea (CDAD) in hospitalized patients with HIV infection, said Jason Flamm, MD, and colleagues, New York Hospital-Cornell Medical Center, New York. The finding emerged in a case-control study of 81 hospitalized patients with HIV infection and CDAD and 86 controls. All case patients were hospitalized on the same day as controls, and CDAD was defined as the presence of a positive stool toxin assay for C. difficile.
Several risk factors for CDAD in the hospitalized patients with HIV infection were similar to those for hospitalized patients without HIV infection including the use of clindamycin and increased length of hospital stay. HIV-associated variables associated with a significantly increased risk of CDAD included CD4 count <100 cells/mm3 and MM or blood transfusions as HIV risk factors versus IVDU and heterosexual activity.
The findings of a study by Joseph Inungu, MD, and colleagues, Louisiana Office of Public Health, New Orleans, contradict previous reports suggesting that clarithromycin and azithromycin prophylaxis or treatment for Mycobacterium avium complex (MAC) is protective against cryptosporidiosis in HIV-infected patients.
The potential protective effects of clarithromycin and azithromycin against HIV-related cryptosporidiosis were determined in 1,281 patients with HIV infection who received either of these drugs for MAC prophylaxis or treatment and 5,195 patients who did not. Overall, 2.9 percent of the patients who did not receive either drug developed cryptosporidiosis compared with 5.4 percent of those who received clarithromycin, 4.8 percent of those who received azithromycin, and 10.5 percent of those taking both drugs. After adjusting for confounding variables, the risk of cryptosporidiosis was increased twofold in patients receiving clarithromycin or azithromycin as compared with those not receiving either drug.
In the months following the First Continental Congress, armed conflicts broke out between the Colonists and British soldiers and the American Revolution was underway. At the Second Continental Congress, held in Philadelphia in May 1775, the delegates named themselves the ruling government and George Washington commander-in-chief of a newly organized army. The army of researchers that continues to battle an adversary far more cunning and resourceful than the British Crown, still has many major battles ahead. But the prize is the same. Freedom from tyranny. This time, the tyranny of a virus that holds the developing world hostage.
David S. MacDougall is a medical writer in New Jersey. email: dsmac@earthlink.net
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This information is designed to support, not replace, the relationship that exists between you and your doctor.