New possibilities for chromoblastomycosis and phaeohyphomycosis treatment: identification of two compounds from the MMV Pathogen Box® that present synergism with itraconazole

BACKGROUND Black fungi of the Herpotrichiellaceae family are agents of chromoblastomycosis and phaeohyphomycosis. There are few therapeutic options for these infections and it is common to associate antifungal drugs in their treatment. OBJECTIVES To investigate the Medicines for Malaria Venture (MMV) Pathogen Box® for possible compounds presenting synergism with antifungal drugs used to treat black fungal infections. METHODS An initial screening of the Pathogen Box® compounds was performed in combination with itraconazole or terbinafine at sub-inhibitory concentrations against Fonsecaea pedrosoi. Hits were further tested against eight Herpotrichiellaceae using the checkerboard method. FINDINGS No synergism was observed with terbinafine. MMV687273 (SQ109) and MMV688415 showed synergism with itraconazole against F. pedrosoi. Synergism of these compounds was confirmed with some black fungi by the checkerboard method. SQ109 and itraconazole presented synergism for Exophiala dermatitidis, F. pedrosoi, F. monophora and F. nubica, with fungicidal activity for F. pedrosoi and F. monophora. MMV688415 presented synergism with itraconazole only for F. pedrosoi, with fungicidal activity. The synergic compounds had high selectivity index values when combined with itraconazole. MAIN CONCLUSIONS These compounds in combination, particularly SQ109, are promising candidates to treat Fonsecaea spp. and E. dermatitidis infections, which account for most cases of chromoblastomycosis and phaeohyphomycosis.

Detection of Drug Resistant Mycobacterium Tuberculosis Strains Using Kit SIRE Nitratase®: a Multicenter Study

Abstract (1) Background: The Commercial Kit SIRE Nitratase® PlastLabor, is a drug susceptibility test kit used to detect Mycobacterium tuberculosis resistance to first-line TB treatment drugs. The present study aimed at evaluating its performance in a multicenter study. (2) Methods: To determine its accuracy, the proportion methods in Lowenstein Jensen medium or the BACTECTMMGITTM960 system was used as a gold standard. (3) Results: The study revealed that the respective accuracies of the kit with 190 M. tuberculosis clinical isolates, using the proportion methods in Lowenstein Jensen medium or BACTECTMMGITTM960 system as a gold standard, were 93.9% and 94.6%, 96.9% and 94.6%, 98.0% and 97.8%, and 98.0% and 98.9%, for streptomycin, isoniazid, rifampicin, and ethambutol, respectively. (4) Conclusion: Thus, the kit can rapidly screen resistance to streptomycin, isoniazid, rifampicin, and ethambutol. Additionally, it does not require sophisticated equipment; hence, it can be easily used in the laboratories of low and middle income countries.

Effect of secondary infection on epithelialisation and total healing of cutaneous leishmaniasis lesions

BACKGROUND Cutaneous leishmaniasis (CL) generally presents with a single or several localised cutaneous ulcers without involvement of mucous membranes. Ulcerated lesions are susceptible to secondary contamination that may slow the healing process. OBJECTIVE This study verified the influence of non-parasitic wound infection on wound closure (epithelialisation) and total healing. METHODS Twenty-five patients with a confirmed diagnosis of CL and ulcerated lesions underwent biopsy of ulcer borders. One direct microbial parameter (germ identification in cultures) and four indirect clinical parameters (secretion, pain, burning sensation, pruritus) were analysed. FINDINGS Biopsies of ten lesions showed secondary infection by one or two microorganisms (Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis, Streptococcus pyogenes and Candida parapsilosis). "Secretion" and "burning sensation" influenced epithelialisation time but not total healing time. Positive detection of germs in the ulcer border and "pain" and "pruritus" revealed no influence on wound closure. CONCLUSIONS Our borderline proof of clinical CL ulcer infection inhibiting CL wound healing supports the need to follow antimicrobial stewardship in CL ulcer management, which was recently proposed for all chronic wounds.

Use of amplified Mycobacterium tuberculosis direct test in respiratory samples from HIV-infected patients in Brazil / Utilização do amplified Mycobacterium tuberculosis direct test em amostras respiratórias de pacientes HIV positivos no Brasil

OBJECTIVE: To compare the accuracy of the amplified Mycobacterium tuberculosis direct (AMTD) test with reference methods for the laboratory diagnosis of tuberculosis in HIV-infected patients. METHODS: This was a study of diagnostic accuracy comparing AMTD test results with those obtained by culture on Löwenstein-Jensen (LJ) medium and by the BACTEC Mycobacteria Growth Indicator Tube 960 (BACTEC MGIT 960) system in respiratory samples analyzed at the Bioassay and Bacteriology Laboratory of the Oswaldo Cruz Foundation Evandro Chagas Clinical Research Institute in the city of Rio de Janeiro, Brazil. RESULTS: We analyzed respiratory samples collected from 118 patients, of whom 88 (74.4%) were male. The mean age was 36.6 ± 10.6 years. Using the AMTD test, the BACTEC MGIT 960 system, and LJ culture, we identified M. tuberculosis complex in 31.0%, 29.7%, and 27.1% of the samples, respectively. In comparison with LJ culture, the AMTD test had a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 89.4%, 75.7%, and 95.0%, respectively, for LJ culture, whereas, in comparison with the BACTEC MGIT 960 system, it showed values of 88.6%, 92.4%, 83.8%, and 94.8%, respectively. CONCLUSIONS: The AMTD test showed good sensitivity and specificity in the population studied, enabling the laboratory detection of M. tuberculosis complex in paucibacillary respiratory specimens. .

OBJETIVO: Comparar a acurácia do teste amplified Mycobacterium tuberculosis direct (AMTD) com métodos de referência para o diagnóstico laboratorial de tuberculose em pacientes HIV positivos. MÉTODOS: Estudo de acurácia diagnóstica comparando os resultados do teste AMTD com os de cultura em Löwenstein-Jensen (LJ) e de BACTEC Mycobacteria Growth Indicator Tube 960 (sistema BACTEC MGIT 960) em amostras respiratórias analisadas no Laboratório de Bacteriologia e Bioensaios do Instituto de Pesquisa Clínica Evandro Chagas da Fundação Oswaldo Cruz, no Rio de Janeiro (RJ). RESULTADOS: Foram analisadas amostras respiratórias de 118 pacientes, dos quais 88 (74,4%) eram do sexo masculino. A média de idade foi de 36,6 ± 10,6 anos. O complexo M. tuberculosis foi identificado em 31,0%, 29,7% e 27,1% das amostras através do teste AMTD, sistema BACTEC MGIT 960 e LJ, respectivamente. Na comparação com a cultura em LJ, o teste AMTD apresentou sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo de 87,5%, 89,4%, 75,7% e 95,0%, respectivamente, enquanto na comparação com o sistema BACTEC MGIT 960, os valores foram de 88,6%, 92,4%, 83,8% e 94,8%, respectivamente. CONCLUSÕES: O teste AMTD mostrou boa sensibilidade e especificidade na população estudada, possibilitando a detecção laboratorial do complexo M. tuberculosis em espécimes respiratórios paucibacilares. .

Factors associated with epidemic multiresistant Pseudomonas aeruginosa infections in a hospital with AIDS-predominant admissions

INTRODUCTION: Infections caused by multiresistant Pseudomonas aeruginosa (MR-PA) have been associated with persistent infections and high mortality in acquired immunodeficiency syndrome (AIDS) patients. Therefore, understanding the predisposing factors for infection/colonization by this agent is critical for controlling outbreaks caused by MR-PA in settings with AIDS patients. OBJECTIVEAND METHODS: To analyze the presence of factors associated with the acquisition of an epidemic MR-PA strain in a hospital with AIDS-predominant admission. A case-control study was carried out in which cases and controls were gathered from a prospective cohort of all hospitalized patients in an infectious disease hospital during a five-year study period. RESULTS: Multivariate logistic regression analysis demonstrated that enteral nutrition OR = 14.9), parenteral nutrition (OR = 10.7), and use of ciprofloxacin (OR = 8.9) were associated with a significant and independent risk for MR-PA acquisition. CONCLUSIONS: Although cross-colonization was likely responsible for the outbreaks, the use of ciprofloxacin was also an important factor associated with the acquisition of an epidemic MR-PA strain. More studies are necessary to determine whether different types of nutrition could lead to modification of gastrointestinal flora, thereby increasing the risk for infection/colonization by MR-PA in this population.

The activity of flavones and oleanolic acid from Lippia lacunosa against susceptible and resistant Mycobacterium tuberculosis strains

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is the world's number one killer among infectious diseases. The search for new naturalproducts that can act as drugs against TB has received increased attention duringthe last years. In this work we describe the isolation and identification of the active antimycobacterial principles of the dichloromethane extract from Lippia lacunosa Mart. & Schauer, Verbenaceae. Compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis (susceptible and rifampicin resistantstrain) using a redox bioassay. From the dichloromethane extract of L. lacunosa leaves, seven methoxy-flavones named cirsimaritin (1), eupatilin (2), eupatorin (3), salvigenin (4), 3'-O-methyl-eupatorin (5), 3',7-dimethoxy-5,6,4'- trihydroxyflavone (6), and 7'-O-methylapigenin (7), and one triterpene, named oleanolic acid (8), were isolated. All compounds were found to display antimycobacterial activity against susceptible strain, with MIC ranging from 25 to 200 µg/mL. None of them was active against rifampicin resistant strain. This is the first report in the antimycobacterial activity of 6-substituted flavones, as well as the first report of the occurrence of these substances in L. lacunosa.

Ethnopharmacological versus random plant selection methods for the evaluation of the antimycobacterial activity

The municipality of Oriximiná, Brazil, has 33 quilombola communities in remote areas, endowed with wide experience in the use of medicinal plants. An ethnobotanical survey was carried out in five of these communities. A free-listing method directed for the survey of species locally indicated against Tuberculosis and lung problems was also applied. Data were analyzed by quantitative techniques: saliency index and major use agreement. Thirty four informants related 254 ethnospecies. Among these, 43 were surveyed for possible antimycobacterial activity. As a result of those informations, ten species obtained from the ethnodirected approach (ETHNO) and eighteen species obtained from the random approach (RANDOM) were assayed against Mycobacterium tuberculosis by the microdilution method, using resazurin as an indicator of cell viability. The best results for antimycobacterial activity were obtained of some plants selected by the ethnopharmacological approach (50 percent ETHNO x 16,7 percent RANDOM). These results can be even more significant if we consider that the therapeutic success obtained among the quilombola practice is complex, being the use of some plants acting as fortifying agents, depurative, vomitory, purgative and bitter remedy, especially to infectious diseases, of great importance to the communities in the curing or recovering of health as a whole.

Outbreaks, persistence, and high mortality rates of multiresistant Pseudomonas aeruginosa infections in a hospital with AIDS-predominant admissions

INTRODUCTION: Authors have reported increased incidence of multiresistant Pseudomonas aeruginosa (MR-PA) infections worldwide over the last decade. Researchers have proposed multifaceted approaches to control MR-PA infections, but none have been reported in the acquired immunodeficiency syndrome (AIDS) setting. OBJECTIVE AND METHODS: Herein we report the impact of a multifaceted intervention for controlling MR-PA over five years in a hospital with AIDS-predominant admissions and describe the clinical characteristics of MR-PA infection in our patient population. The clinical outcomes of infected patients and molecular characteristics of the isolated strains were used as tools for controlling MR-PA infection rates. RESULTS: Significant temporary decrease of new infections was achieved after intervention, although a high level of diagnostic suspicion of nosocomial infection was maintained. We obtained 35 P. aeruginosa isolates with multiresistant profiles from 13 infected and 3 colonized patients and 2 environmental samples. Most of the patients (94 percent) were immunocompromised with AIDS (n = 10) or HTLV-1 infections (n = 5). Of the followed patients, 67 percent had persistent and/or recurrent infections, and 92 percent died. We observed differences in the antibiotic-resistance pattern of MR-PA infection/colonization during two outbreaks, although the genetic profiles of the tested strains were identical. CONCLUSIONS: Therefore, we concluded that early multidisciplinary interventions are essential for reducing the burden caused by this microorganism in patients with AIDS. Prolonged or suppressive antibiotic-based therapy should be considered for MR-PA infections in patients with AIDS because of the persistence characteristic of MR-PA in these patients.

Effectiveness of highly active antiretroviral therapy (HAART) used concomitantly with rifampicin in patients with tuberculosis and AIDS

This study evaluated the effectiveness of two HAART regimens concomitant to rifampicin based tuberculosis (TB) treatment. Patients with TB/HIV diagnosis followed at the TB program between June 2000 and March 2005 were prospectively evaluated. The different HAART regimens in antiretrovirals (ARV) treatment naïve and ARV experienced patients were compared. The effectiveness of HAART was defined as a VL <80 copies/mL from month 4 to month 10 after TB treatment. One hundred and forty-two patients were included. Among these, 68 (47 percent) were treatment naïve and 76 (53 percent) previously exposed. Odds ratio (OR) in naïve patients treated with efavirenz (EFV) based regimen (n=42) compared to ritonavir/saquinavir (RTV/SQV) based regimen (n=26) was 8.0 (CI=1.67-38.35, p=0.008). OR from ARV experienced patients treated with RTV/SQV based regimen compared to EFV was 3.08 (CI=0.65-14.6, p=0.15), although with no statistical significance. Better effectiveness and tolerability were observed in antiretrovirals treatment naïve patients using EFV based regimens. Although not statistically significant, a favorable virologic response and a better tolerability were observed in the ARV experienced patients group who received a RTV/SQV based regimen.

Preparation and antitubercular activity of lipophilic diamines and amino alcohols

A series of diamines and amino alcohols derived from 1-dodecanol, 1-tetradecanol, 1,2-dodecanediol and 1,2-tetradecanediol were synthesized and tested for their antitubercular activity. Compounds 3, 8 and 9 were found to be the most active (MIC of 6.25 µg/mL). Nine other compounds displayed activity against Mycobacterium tuberculosis, with a MIC of 12.5 µg/mL.

Molecular diversity of Mycobacterium tuberculosis strains in a slum area of Rio de Janeiro, Brazil / Diversidade molecular de cepas de Mycobacterium tuberculosis em uma região de favela da cidade do Rio de Janeiro

This retrospective molecular study involving restriction fragment length polymorphism, using insertion sequence 6110 as a marker, was conducted in order to provide an initial insight into the genetic diversity of Mycobacterium tuberculosis strains isolated in the slums of the Complexo de Manguinhos, located in the city of Rio de Janeiro, Brazil. Of the 67 strains evaluated, 23 (34.3 percent) were found to belong to clusters (total clusters, 10). Household and social chains of transmission were associated with clustering, in 20 percent and 60 percent, respectively. Living in the Conjunto Habitacional Programado 2 slum was associated with clustering. Although not significant, it is relevant that 26 percent of the clustered strains presented primary resistance. These findings, although possibly underestimating the prevalence due to the failure to analyze all strains, could help improve the local tuberculosis control program.

Este estudo retrospectivo envolvendo polimorfismo de fragmento de restrição e utilizando como marcador a seqüência de inserção 6110, foi realizado para fornecer informações iniciais quanto à diversidade genética das cepas de Mycobacterium tuberculosis isoladas em favelas do Complexo de Manguinhos, na cidade do Rio de Janeiro. Das 67 cepas isoladas, 23 (34,3 por cento) foram agrupadas em clusters (total de clusters, 10). A transmissão entre comunicantes domiciliares e extra-domicialiares estave associada a 20 por cento e 60 por cento dos clusters, respectivamente. Ser morador do Conjunto Habitacional Programado 2 foi associado à presença de clusters. Embora não significativo, é relevante o fato de que 26 por cento das cepas em cluster apresentaram resistência primária. Estes achados, embora possivelmente subestimados devido à impossibilidade de analisar todas as cepas, fornecem subsídios para a melhoria do programa local de controle da tuberculose.

Resistência a drogas em cepas de mycobacterium tuberculosis isoladas de amostras de escarro de pacientes ambulatoriais sintomáticos: Complexo de Manguinhos, Rio de Janeiro, Brasil / Drug resistance in mycobacterium tuberculosis strains isolated from sputum samples from symptomatic outpatients: Complexo de Manguinhos, Rio de Janeiro, Brazil

Para descrever a resistência a drogas em cepas de Mycobacterium tuberculosis isoladas de amostras de escarro de 263 pacientes suspeitos de tuberculose moradores do Complexo de Manguinhos, Rio de Janeiro, Brasil, as culturas positivas entre outubro de 2000 e dezembro de 2002 foram submetidas a teste de sensibilidade para isoniazida, rifampicina, estreptomicina, etionamida e etambutol. Resistência a qualquer das drogas foi encontrada em 21,4 por cento (16/75) dos pacientes diagnosticados com tuberculose. Destes, 50 por cento (8/16) eram casos novos e 50 por cento (8/16) eram casos com tratamento anterior. A tuberculose multirresistente foi encontrada em 10,6 por cento (8/75) do total de pacientes, estando associada a tratamento anterior em 8 por cento (6/75) deles. Nossos resultados podem ter sido subestimados, pois M. tuberculosis não pôde ser isolado em todas as amostras positivas para bacilos álcool-ácido resistentes. Contudo, eles pelo menos revelam parte do problema.

This study aimed to assess drug resistance in Mycobacterium tuberculosis strains isolated from sputum samples. To that end, sputum samples were collected from 263 patients suspected of having tuberculosis. All subjects lived in the Complexo de Manguinhos, which is located in the city of Rio de Janeiro, Brazil. Cultures testing positive between October of 2000 and December of 2002 were tested to determine strain susceptibility to isoniazid, rifampicin, streptomycin, ETHionamide, and ETHambutol. Of the 75 patients diagnosed with tuberculosis, resistance to at least one of the drugs was found in 16 (21.4 percent). Of those 16 patients, 8 (50 percent) were new cases, and 8 (50 percent) had previously been treated. Multidrug-resistant tuberculosis was identified in 8 (10.6 percent) of the 75 patients, being associated with previous treatment in 6 (8 percent). The incidence of multidrug-resistant tuberculosis might have been underestimated, since M. tuberculosis was not isolated from all of the samples testing positive for acid-fast bacilli. However, at least, our findings shed some light on the problem.

Um estudo retrospectivo dos aspectos epidemiológicos da tuberculose na comunidade do Complexo de Manguinhos localizado em área urbana do Rio de Janeiro, Brasil, 2000-2002 / A retrospective study of the epidemiological aspects of tuberculosis in the Complexo de Manguinhos, an urban slum area in Rio de Janeiro, Brazil, 2000-2002

To describe some aspects of tuberculosis in a low-income community (the Complexo de Manguinhos, in Rio de Janeiro, Brazil), a retrospective study was carried out. Of the 290 cases reported in the 2000-2002 period, 75.8 percent were new cases. The annual incidence rates were 157/100,000 (2000), 205/100,000 (2001), and 145/100,000 (2002). Although there was a tendency toward a decrease in the number of cases over the period studied, the difference was not significant, suggesting that tuberculosis continues to be endemic in the area. Therefore, despite the existence of local public health care services, more efficient strategies should be implemented in order to increase the effectiveness of tuberculosis control programs in the area.

Para descrever alguns aspectos da tuberculose em favelas, foi realizado um estudo retrospectivo no Complexo de Manguinhos, Rio de Janeiro (RJ) Brasil. Em um total de 290 casos notificados entre 2000 e 2002, 75,8 por cento eram casos novos. A taxa de incidência foi de 157, 205 e 145/100.000, respectivamente. Embora tenha sido observada tendência de diminuição dos números de casos no período de estudo, esta não foi significante, sugerindo manutenção da endemia. Portanto, embora exista um serviço de saúde no local, estratégias mais eficientes devem ser implantadas para auxiliar o Programa de Controle da tuberculose.

Subclinical infection of the genital tract with Neisseria meningitidis

We report the isolation of Neisseria meningitidis, characterized as B:NT:P1.7, from a female patient's genital tract in an outpatient clinic for HIV care. The gynecology clinic, as part of the follow up, collects specimens from all patients with HIV infection for routine exams and for early laboratory detection of sexually transmitted diseases . A Gram-negative diplococcus was isolated from the cervix of a heterosexual patient with AIDS. Based on this and other reported cases, urogenital infection with N. meningitidis can no longer be considered uncommon. The rising incidence of N. meningitidis isolated from this and similar sites has significant medical and diagnostic implications.

Screening of Central and South American plant extracts for antimycobacterial activity by the Alamar Blue test / Triagem de extratos de plantas das Américas Central e do Sul para atividade antimicobacteriana pelo teste do Alamar Blue

Forty eight ethanolic crude extracts and fractions (hexane, dichloromethane, ethyl acetate and n-butanol) from ten Brazilian plants (Leguminosae, Monimiaceae and Verbenaceae), 1 from Costa Rica (Verbenaceae) and 1 from Argentina (Verbenaceae) were screened for anti-mycobacterium activity against Mycobacterium tuberculosis (ATCC-27294H37Rv), by the Alamar Blue test, at a fixed concentration of 100 µg/mL. Out of the forty eight, seven were active at this concentration, corresponding to Lantana trifolia (hexane and dichloromethane extracts from leaves), Vitex cooperi (methanol:water, 1:1 extract from barks), Lippia lacunosa (hexane and dichloromethane extracts from leaves) and Lippia rotundifolia (hexane and dichloromethane extracts from leaves), all from the Verbenaceae family.

Quarenta e oito extratos brutos etanólicos e frações (em hexano, diclorometano, acetato de etila e n-butanol) de dez plantas brasileiras pertencentes às famílias Leguminosae, Monimiaceae e Verbenaceae; uma da Costa Rica (Verbenaceae) e uma da Argentina (Verbenaceae) foram ensaiados para verificação da atividade anti-micobacteriana contra Mycobacterium tuberculosis (ATCC-27294H37Rv), pelo teste do Alamar Blue, a uma concentração fixa de 100 µg/mL. Dentre os quarenta e oito extratos e frações estudados, sete mostraram-se ativos na concentração ensaiada - frações em hexano e diclorometano de folhas de Lantana trifolia, extrato em metanol:água, 1:1 de cascas de Vitex cooperi, frações em hexano e diclorometano de folhas de Lippia lacunosa e de Lippia rotundifolia, sendoque todas essas plantas pertencem à família Verbenaceae.

Salmonella enterica subsp houtenae serogroup O:16 in a HIV positive patient: case report

Descreve-se um caso clínico de salmonelose ocorrido em paciente HIV positivo de 33 anos, portador de candidíase oral e esofágica, com intensa dor abdominal superior e dor retro-esternal. Ao exame clínico apresentou-se hipocorado, acianótico, hipohidratado, anictérico e afebril. A investigação laboratorial na admissão apresentou: hemácias, 3,6 milhões/mm3; hemoglobina, 10,1 g/dL; contagem de leucócitos, 3.000/mm3, com 1 de eosinófilos, 14 de bastões; 53 de neutrófilos segmentados e 31 de linfócitos. A hemocultura foi positiva para Salmonella enterica subsp houtenae sorogrupo O:16. Provavelmente, este é o primeiro relato de caso clínico humano com bacteremia causado por Salmonella enterica subsp houtenae no Brasil associado a paciente HIV-infectado.

Low incidence of colonization and no cases of disseminated Mycobacterium avium complex infection (DMAC) in Brazilian AIDS patients in the HAART era

OBJECTIVE: Evaluate the incidence of mycobacterial disease and the colonization of the respiratory and gastrointestinal tracts by Mycobacterium avium complex (MAC) bacteria in AIDS patients. METHODS: Inclusion criteria: HIV-positive individuals with at least one CD4+ count < 100 cells/mm³. Exclusion criteria: Mycobacterial disease and MAC prophylaxis. Stool, sputum, and blood cultures were prospectively obtained every month from September, 1997, to December, 1999. The incidence was calculated using Poisson regression. Survival was estimated by the Kaplan Meier method and the Cox proportional hazard model. RESULTS: We followed-up 79 patients during a median period of 428 days. Blood cultures (n = 742) were negative for all mycobacteria. Positive cultures (25 samples) were obtained from non-sterile sites: Stools (19/703 specimens = 2.7 percent) and sputum (14/742 specimens = 1.9 percent). MAC was isolated in 7/703 stool samples (1 percent) and 1/32 sputum specimens (0.1 percent). The incidence of patient colonization with MAC was 0.09 /year (CI=0.05 - 0.18). CD4 counts in patients colonized with MAC were below 100 cells/mm³ in only 2 out of 8 cases. Restoration of CD4+ counts >100 cells/mm³ (HR = 0.18; CI = 0.05 - 0.70) predicted a lower risk of death (P<0.05) but was not protective for MAC colonization (HR=0.52;CI =0.62 - 4.35, P=0.55). CONCLUSION: The absence of DMAC infection in colonized individuals argues in favor of a HAART protective effect against; DMAC; however, restoration of CD4 counts did not protect patients against MAC colonization