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1.
Treatment of pulmonary tuberculosis.
Nunn, A, Phillips, PP, Abubakar, I
Current opinion in pulmonary medicine. 2013;(3):273-9
Abstract
PURPOSE OF REVIEW Despite reduction in incidence in several regions, tuberculosis (TB) remains a pandemic of world-wide significance. There is an urgent need to develop better regimens, to shorten treatment and to effectively manage both drug-sensitive and drug-resistant disease. RECENT FINDINGS There has been a substantial increase in numbers of drugs in the development pipeline and two of the candidates are expected to receive widespread accelerated approval for the treatment of multidrug-resistant TB (MDR-TB). An important determining factor in the choice of regimens for phase III is the speed with which patients become culture negative during treatment, measured as either time to culture conversion or culture negativity at a given time point. It is impossible to consider the treatment of TB in sub-Saharan Africa without considering the patients who are coinfected with HIV, and the decision of when to commence treatment with antiretrovirals is critical. What, if any, is the role of adjunctive treatments such as vitamin D? SUMMARY In this review, we describe the encouraging data on a number of drugs which are about to enter phase II or phase III trials, results from trials of standard regimens in close to programme conditions and a series of trials highlighting the importance of an early commencement of antiretroviral treatment.
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Idiopathic AIDS enteropathy and treatment of gastrointestinal opportunistic pathogens.
Cello, JP, Day, LW
Gastroenterology. 2009;(6):1952-65
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Abstract
Diarrhea in patients with acquired immune deficiency syndrome (AIDS) has proven to be both a diagnostic and treatment challenge since the discovery of the human immunodeficiency virus (HIV) virus more than 30 years ago. Among the main etiologies of diarrhea in this group of patients are infectious agents that span the array of viruses, bacteria, protozoa, parasites, and fungal organisms. In many instances, highly active antiretroviral therapy remains the cornerstone of therapy for both AIDS and AIDS-related diarrhea, but other targeted therapies have been developed as new pathogens are identified; however, some infections remain treatment challenges. Once identifiable infections as well as other causes of diarrhea are investigated and excluded, a unique entity known as AIDS enteropathy can be diagnosed. Known as an idiopathic, pathogen-negative diarrhea, this disease has been investigated extensively. Atypical viral pathogens, including HIV itself, as well as inflammatory and immunologic responses are potential leading causes of it. Although AIDS enteropathy can pose a diagnostic challenge so too does the treatment of it. Highly active antiretroviral therapy, nutritional supplementation, electrolyte replacements, targeted therapy for infection if indicated, and medications for symptom control all are key elements in the treatment regimen. Importantly, a multidisciplinary approach among the gastroenterologist, infectious disease physician, HIV specialists, oncology, and surgery is necessary for many patients.
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Dermatologic adverse effects of antiretroviral therapy: recognition and management.
Luther, J, Glesby, MJ
American journal of clinical dermatology. 2007;(4):221-33
Abstract
Despite the decrease in opportunistic infections associated with HIV in the highly active antiretroviral treatment (HAART) era, a significant number of patients still present with skin pathology, some of which can be attributed directly or indirectly to antiretroviral therapy. The non-nucleoside reverse transcriptase inhibitors exhibit a class effect with regard to skin adverse manifestations, and the spectrum of disease can vary from a mild morbilliform rash to Stevens-Johnson syndrome. Certain protease inhibitors are associated with rash, and indinavir causes retinoid-like manifestations such as paronychia, alopecia, ingrown toe-nails, and curling of straight hair. Abacavir, a nucleoside reverse transcriptase inhibitor, is notorious for causing a hypersensitivity reaction in select patients. The fusion inhibitor enfuvirtide causes injection-site reactions in the overwhelming majority of patients, although a new method of delivery has decreased the rate and severity of these reactions. A syndrome of lipoatrophy with or without lipohypertrophy, often termed lipodystrophy, has been described in patients receiving HAART. Potential management of lipoatrophy includes switching antiretrovirals and surgical treatment with facial fillers. Lastly, skin manifestations of the immune reconstitution inflammatory syndrome, including herpes zoster and warts, must be recognized and treated accordingly. In the evaluation of the individual HIV-infected patient receiving antiretroviral therapy who presents with a skin disorder, clinicians should consider the CD4 cell count as a marker of the degree of immunodeficiency, the specific antiretrovirals used, and the timing of the initiation of antiretroviral therapy in order to formulate a rational differential diagnosis. Management should be individualized based on the specific drug that is implicated and the severity of the reaction.
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4.
Treatment Options for HIV-Associated Tuberculosis.
Onyebujoh, PC, Ribeiro, I, Whalen, CC
The Journal of infectious diseases. 2007;(Suppl 1):S35-45
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Abstract
The vicious interaction between the human immunodeficiency virus (HIV) infection and tuberculosis (TB) pandemics poses special challenges to national control programs and individual physicians. Although recommendations for the treatment of TB in HIV-infected patients do not significantly differ from those for HIV-uninfected patients, the appropriate management of HIV-associated TB is complicated by health system issues, diagnostic difficulties, adherence concerns, overlapping adverse-effect profiles and drug interactions, and the occurrence of paradoxical reactions after the initiation of effective antiretroviral therapy. In this article, recommended treatment strategies and novel approaches to the management of HIV-associated TB are reviewed, including adjuvant treatment and options for treatment simplification. A focused research agenda is proposed in the context of the limitations of the current knowledge framework.
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Management of blinding disease: loss of immunity and superinfection.
Evans, BG
Eye (London, England). 2005;(10):1035-6
Abstract
Globally the most important loss of immunity currently occurs with HIV disease. The effects of HIV on the eye, since the advent of highly active antiretroviral therapy, have been less in countries where such treatment is available but even in such situations ophthalmic zoster can occur at higher CD4 cell counts and can still cause problems. Other opportunistic infections such as CMV retinitis tend to occur at lower CD4 cell counts. However, globally treatment is not universally available in resource poor countries where it is most needed. A major impact of HIV in such situations is on premature mortality affecting the health care and education workforce, which indirectly has an impact on blinding disease. In addition, loss of family income due to illness or death of parents can affect nutritional status of remaining family members especially children as well as the direct effect of opportunistic infections in the eyes of those infected with HIV.
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Special considerations in the initiation and management of antiretroviral therapy in individuals coinfected with HIV and hepatitis C.
Braitstein, P, Palepu, A, Dieterich, D, Benhamou, Y, Montaner, JS
AIDS (London, England). 2004;(17):2221-34
Abstract
BACKGROUND Although hepatitis C (HCV) treatment efficacy has improved in recent years, the majority of HIV/HCV-coinfected individuals may not enjoy the full benefits of these treatments and appropriate HIV management is crucial. Evidence is accumulating regarding the impact of HIV/HCV coinfection on the response to, and safety and tolerability of, antiretroviral therapy (ART) in this population. METHODS Computerized, English-language literature searches of MEDLINE and PubMed databases (January 1985 to May 2004) for studies of HIV and HCV infection in humans to examine critically (a) the impact of HCV on the HIV virologic and immunologic response to ART; (b) the safety and tolerability of ART in coinfected individuals; and (c) the relationship between immune suppression and immune restoration on hepatic injury. RESULTS Three key messages emerged regarding the use of ART in HIV/HCV-coinfected individuals: (a) although HCV appeared to have no impact on HIV virologic response, the data are equivocal regarding immunologic response; (b) morbidities associated with HCV infection, such as insulin resistance, diabetes, mitochondrial dysfunction, and liver inflammation, are also associated toxicities of ART, and (c) both immune suppression and restoration can contribute to the onset and acceleration of HCV-related liver disease. CONCLUSIONS The CD4 cell count threshold for initiating ART in HIV/HCV-coinfected patients may be higher because of the impact of immune suppression and restoration on the onset of HCV-associated liver disease and the possibility of a blunted immune response to ART at lower CD4 cell counts. Further, overlapping morbidity between HCV-related mitochondrial and metabolic disease manifestations and ART toxicities warrant careful attention by clinicians.
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A systematic review of the management of oral candidiasis associated with HIV/AIDS.
Albougy, HA, Naidoo, S
SADJ : journal of the South African Dental Association = tydskrif van die Suid-Afrikaanse Tandheelkundige Vereniging. 2002;(11):457-66
Abstract
The purpose of this review was to investigate the management of oral candidiasis in HIV/AIDS patients and to evaluate the different guidelines available for its management. A number of topical and systemic antifungal medications are used to treat oral candidiasis in HIV-positive patients. Milder episodes of oral candidiasis respond to topical therapy with nystatin, clotrimazole troches or oral ketoconazole. Fluconazole has been extensively evaluated as a treatment for candidiasis. With HIV-infection, a cure rate of 82% has been achieved with a daily oral dose of 50 mg. Fluconazole was found to be a better choice of treatment for relapsing oropharyngeal candidiasis, resulting in either better cure rates or better prevention of relapse. Intravenous amphotericin B has been found to be effective in azole-refractory candidiasis and is well tolerated. Topical therapies are effective for uncomplicated oropharyngeal candidiasis; however, patients relapsed more quickly than those treated with oral systemic antifungal therapy. Nystatin appeared less effective than clotrimazole and the azoles in the treatment of oropharyngeal candidiasis. Clotrimazole was found to be just as effective for resolution of clinical symptoms as the azoles, except when patient compliance was poor. Fluconazole-treated patients were more likely to remain disease-free during the fluconazole follow-up period than those treated with other antifungal agents.
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Oral fungal and bacterial infections in HIV-infected individuals: an overview in Africa.
Hodgson, TA, Rachanis, CC
Oral diseases. 2002;:80-7
Abstract
Oral opportunistic infections developing secondary to human immunodeficiency virus (HIV) infection have been reported from the early days of the epidemic and have been classified by both the EC-Clearinghouse and the World Health Organisation (WHO). Among the fungal infections, oral candidiasis, presenting in African HIV-infected patients has been sporadically documented. We review the literature with respect to candidal carriage, oral candidiasis prevalence and the predictive value of oral candidiasis for a diagnosis of underlying HIV disease in African HIV-infected patients. The use of oral candidiasis as a marker of disease progression, the species of yeasts isolated from the oral cavity in Africa and the resistance of the yeasts to antifungal agents and treatment regimens are discussed. Orofacial lesions as manifestations of the systemic mycoses are rarely seen in isolation and few cases are reported in the literature from Africa. In spite of the high incidence of noma, tuberculosis, chronic osteomyelitis and syphilis in Africa, surprisingly there have been very few reported cases of the oral manifestations of these diseases in HIV-positive individuals. Orofacial disease in HIV-infected patients is associated with marked morbidity, which is compounded by malnutrition. The authors indicate specific research areas, initially directed at the most effective management strategies, which would complete data in this important area.
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Recent advances in the treatment of AIDS-related Kaposi's sarcoma.
Cattelan, AM, Trevenzoli, M, Aversa, SM
American journal of clinical dermatology. 2002;(7):451-62
Abstract
Kaposi's sarcoma (KS) is the most common malignancy associated with HIV infection and is considered an AIDS defining condition by the US Centers of Disease Control Guidelines. Several advances in the treatment of AIDS-related KS have been achieved over the past few years, even though a gold standard therapy for KS has not yet been defined and treatment must be tailored to individual needs. Since the availability of highly active antiretroviral therapy (HAART), a dramatic clinical response has been documented in patients with KS, making HAART an essential approach in the management of KS in most, if not all, patients with AIDS-related KS. However, in case of aggressive, visceral, and/or life-threatening KS, more complex therapeutic schedules have to be taken into account, including chemotherapy, radiotherapy, and/or immunotherapy. In general, systemic treatment for KS is limited to widespread, symptomatic disease, whereas local interventions are indicated for minimal, cosmetically troublesome lesions. Among new cytotoxic agents, liposomal anthracyclines and paclitaxel are highly effective molecules for KS and have been approved by the US Food and Drug Administration (FDA) as first-line and second-line monotherapy, respectively, for advanced KS. Furthermore, a greater understanding of the pathogenesis of KS has lead to the development of an array of new experimental agents. Many antiangiogenic agents such as AGM 1470 (TNP 470), thalidomide, and glufanide disodium (IM 862) have produced encouraging responses in patients with KS and large clinical trials are in progress. Retinoic acids may also block neoangiogenesis as well as proliferation of KS cells in vitro, and they have been used either systemically or topically with a high response rate. Thus, a topical compound 0.1% alitretinoin gel was approved in 1999 by the FDA for the treatment of skin lesions associated with KS. Human chorionic gonadotropin, a hormonal agent, has shown a strong inhibitory activity in KS cells, but its role in the regression of KS lesions is not clear. Finally, the identification of a novel gamma-herpesvirus, human herpesvirus-8, as a causative agent for KS, together with novel antiangiogenic compounds, such as metalloproteinase inhibitors, may offer promising targets for the therapy of KS.
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Epidemiological evidence and molecular basis of interactions between HIV and JC virus.
Berger, JR, Chauhan, A, Galey, D, Nath, A
Journal of neurovirology. 2001;(4):329-38