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Nine months of daily isoniazid is efficacious in treating latent M. tuberculosis infection, but completion rates are low, limiting treatment effectiveness. In 2011, three important studies were published involving novel regimens for the treatment of latent M. tuberculosis infection. At least 36 months of isoniazid was more effective than 6 months of isoniazid in one study, but not in another-both of which were conducted among tuberculin skin test positive HIV-infected adults living in high tuberculosis incidence settings. Three months of once-weekly isoniazid plus rifapentine or twice-weekly isoniazid plus rifampin (both given under direct observation) resulted in tuberculosis rates similar to those seen with 6 months of isoniazid among HIV-infected persons in high tuberculosis incidence settings. Three months of once-weekly, directly-observed isoniazid plus rifapentine was at least as effective as 9 months of daily isoniazid among predominantly HIV-uninfected persons living in low and medium tuberculosis incidence countries. The 3-month once-weekly isoniazid plus rifapentine regimen demonstrates promise for treatment of latent M. tuberculosis infection in HIV-infected persons.
BACKGROUND - Introduction of highly active antiretroviral therapy (HAART) has resulted in a significant decrease of oral manifestations (OMs). The profile and risk factors for OM in those individuals initiating HAART remain understudied in the Southeast of the United States, region of increasing HIV prevalence.
OBJECTIVE - To determine clinical, socio-demographic, and laboratory characteristics associated with the presence of OM among patients initiating HAART.
METHODS - Retrospective review of electronically captured data from patients initiating HAART at a Southeastern US clinic. Prevalence was determined, and risk factors for overall OM, oropharyngeal candidiasis (OPC), and all other OM were evaluated using logistic regression.
RESULTS - In our sample (n = 744), majority of individuals were males (75 percent), African-American (50 percent), mean age of 39 years, 42 percent of which reported sex with men (MSM). Two hundred sixty-six had some type of OM. Compared with those without any OM, patients with OM had a lower mean baseline CD4+ T cells count (CD4 count) (331 ± 260 versus 179 ± 244 CD4 cells/mm(3) ) and higher mean baseline HIV-1 RNA viral load (4.0 ± 1.34 log(10) versus 4.6 ± 1.30 log(10) ) (P < 0.01). In the logistic regression models seeking to determine factors associated with an increased risk of OM and OPC, the only characteristic associated with the outcome was baseline CD4 value. Being male, African-American, and heterosexual showed a protective role for OM other than OPC.
CONCLUSION - OM continues to be common despite HAART. General OM and OPC were closely associated with a low baseline CD4 count. Knowledge of risk factors for OM can potentially help clinicians target oral evaluation of HIV-positive individuals.
© 2011 American Association of Public Health Dentistry.
Using a novel blinded intrapatient vehicle control design, we conducted a phase II study of topically administered halofuginone, an angiogenesis inhibitor that inhibits collagen type-I and matrix metalloproteinases (MMPs), in patients with AIDS-related Kaposi sarcoma. Serial Kaposi sarcoma biopsies assessed treatment effects on angiogenic factors and Kaposi sarcoma herpesvirus-latency associated nuclear antigen-1 (KSHV-LANA). We observed marked heterogeneity of KSHV-LANA expression. Although the small number of subjects whose response could be evaluated precluded definitive assessment of halofuginone's efficacy, we observed a significant decrease in type-I collagen only in halofuginone-treated lesions, but no effect on MMP-2. The trial design is applicable to future studies of topical agents.
SETTING - Urban tuberculosis (TB) clinic, Nashville, Tennessee, USA.
OBJECTIVE - Chest radiographs (CXRs) help in the diagnosis of pulmonary TB, but may be normal. Mycobacterium tuberculosis in culture is diagnostic of TB, but cultures are not routinely obtained in resource-poor settings. We examined rates and risk factors for pulmonary TB associated with normal CXR.
DESIGN - An observational cohort study was performed among all respiratory culture-positive TB cases referred to the Nashville Health Department from October 1992 to July 2003. Clinical factors, demographics and underlying medical conditions were assessed.
RESULTS - Of 601 study patients, 53 (9%) had normal CXRs: 31/138 (22%) were human immunodeficiency virus (HIV) infected and 22/463 (5%) were non-HIV-infected/unknown (P<0.001). Among HIV-infected patients, normal CXR was more likely in persons with renal failure (13% vs. 3%, P=0.048). Among non-HIV-infected/unknown patients, normal CXR was more likely in those who were asymptomatic at presentation (32% vs. 13%, P=0.022). In multivariable logistic regression analysis, HIV infection was associated with an increased risk of normal CXR (odds ratio [OR] 6.61, P<0.0001); factors associated with reduced risk were dyspnea (OR 0.24, P=0.026), positive sputum smear (OR 0.45, P=0.028) and cough (OR 0.48, P=0.038).
CONCLUSIONS - The rate of normal CXR among persons with culture-confirmed pulmonary TB was high. Respiratory specimen cultures should be obtained in TB suspects with a normal CXR, particularly HIV-infected persons.
OBJECTIVE - Tuberculosis is the major opportunistic infection of HIV/AIDS in developing countries. We investigated the prevalence rate of multidrug-resistant (MDR) tuberculosis at an HIV voluntary counseling and testing (VCT) center in Port-au-Prince, Haiti.
DESIGN AND METHODS - A cross-sectional prevalence study of MDR-tuberculosis was conducted at a VCT Center. All patients reporting at least 5 days of cough were screened for tuberculosis, including sputum culture. All Mycobacteria tuberculosis isolates underwent drug susceptibility testing.
RESULTS - Between January 2000 and December 2002, isolates from 330 patients underwent drug susceptibility testing. MDR-tuberculosis was documented in 16 (6%) of 281 patients with primary tuberculosis and 10 (20%) of 49 patients with recurrent tuberculosis. In patients with primary disease, 11 (10%) of 115 HIV-infected patients had MDR-tuberculosis compared with five (3%) of 166 HIV-negative patients, (risk ratio 3.2; 95% confidence interval 1.1-8.9; P = 0.0331).
CONCLUSION - Multidrug resistance was prevalent among patients found to have pulmonary tuberculosis at an HIV testing center in Port-au-Prince. Patients with primary pulmonary tuberculosis who were HIV-co-infected were more likely to have multidrug resistance than HIV-negative patients. Assiduous attention to tuberculosis infection control measures at HIV testing centers in developing countries is critical to prevent nosocomial MDR-tuberculosis transmission. Measures may include appropriate ventilation, outdoor seating, ultra-violet lights, and rapid on-site screening for tuberculosis.
Sub-Saharan Africa is disproportionately burdened by intestinal helminth and human immunodeficiency virus (HIV)-1 infection. Recent evidence suggests detrimental immunologic effects from concomitant infection with the two pathogens. Few studies, however, have assessed the prevalence of and predictors for intestinal helminth infection among HIV-1-infected adults in urban African settings where HIV infection rates are highest. We collected and analyzed sociodemographic and parasitologic data from 297 HIV-1-infected adults (mean age = 31.1 years, 69% female) living in Lusaka, Zambia to assess the prevalence and associated predictors of helminth infection. We found at least one type of intestinal helminth in 24.9% of HIV-infected adults. Thirty-nine (52.7%) were infected with Ascaris lumbricoides, and 29 (39.2%) were infected with hookworm. More than 80% were light-intensity infections. A recent visit to a rural area, food shortage, and prior history of helminth infection were significant predictors of current helminth status. The high helminth prevalence and potential for adverse interactions between helminths and HIV suggests that helminth diagnosis and treatment should be part of routine HIV care.
BACKGROUND - A consensus conference was held to discuss priorities for antiretroviral therapy (ART) research in Zambia, one of the world's most heavily HIV-afflicted nations. Zambia, like other resource-limited settings, has increasing access to highly active antiretroviral therapy (HAART) because of declining drug costs, use of government-purchased generic medications, and increased global donations. For sustained delivery of care with HAART in a resource-constrained medical and public health context, operational research is required and clinical trials are desirable. The priority areas for research are most relevant today given the increasing availability of HAART.
METHODS - A conference was held in Lusaka, Zambia, in January 2002 to discuss priority areas for ART research in Zambia, with participants drawn from a broad cross section of Zambian society. State-of-the-art reviews and 6 intensive small group discussions helped to formulate a suggested research agenda.
RESULTS - Conference participants believed that the most urgent research priorities were to assess how therapeutic resources could be applied for the greatest overall benefit and to minimize the impact of nonadherence and viral resistance. Identified research priorities were as follows:Conference participants recommended that HIV-related clinical care and research be integrated within home-based care services and operated within the existing health delivery structures to ensure sustainability, reduce costs, and strengthen the structures.
CONCLUSION - Our consensus was that antiretroviral clinical trials and operational research are essential for Zambia to address the new challenges arising from increasing ART availability. There is global consensus that antiretroviral clinical trials in resource-constrained countries are possible, and the capacity for such trials should be developed further in Africa.
Pneumocystis carinii pneumonia (PCP) remains the most common opportunistic infection among human immunodeficiency virus-infected persons. Despite this, little is known concerning the transmission dynamics of this infection. In the absence of a reliable method to isolate and culture P. carinii from environmental samples, it has not been possible to assess the importance of person-to-person transmission in the epidemiology of PCP. A molecular viability assay was developed for the human form of P. carinii (P. carinii f sp hominis) that is applicable to both clinical specimens and environmental samples. This assay will enable the evaluation of the spread and persistence of viable human P. carinii in the environment.
We compared Roche MONITOR and Organon Teknika NucliSens assays for human immunodeficiency virus type 1 (HIV-1) RNA in cerebrospinal fluid (CSF). Results of 282 assays were highly correlated (r = 0.826), with MONITOR values being 0.29 +/- 0.4 log(10) copies/ml (mean +/- standard deviation) values. Both assays can reliably quantify HIV-1 RNA in CSF.
BACKGROUND - Histochemical staining of bone marrow biopsy samples for microorganisms may provide a presumptive diagnosis weeks before culture.
METHODS - To identify predictors of histochemical positivity, we reviewed 161 bone marrow biopsies from febrile patients with human immunodeficiency virus (HIV) infection.
RESULTS - By multivariate analysis, both hematocrit value <30% and white blood cell count <4,000/mm3 predicted biopsy positivity by culture or staining, but only anemia predicted histochemical stain positivity. Of cases with serum lactate dehydrogenase (LDH) levels >600 U/L, histoplasmosis was diagnosed in 31.6% versus 7.8% with lower LDH levels. Among histoplasmosis cases, staining showed fungi in all, with LDH levels >600 U/L versus 44.4% with lower levels.
CONCLUSIONS - Bone marrow biopsy will most likely provide a rapid diagnosis in patients with anemia. Markedly elevated LDH levels suggest stain positivity for Histoplasma capsulatum. Histopathologic patterns may also guide empiric therapy.