Multicentre derivation and validation of a prognostic scoring system for mortality assessment in HIV-infected patients with talaromycosis.

BACKGROUND: Although the widespread use of modern antiretroviral therapy (ART) has reduced the incidence of talaromycosis in people living with HIV, mortality remains as high as 20% in this population, even after appropriate antifungal treatment. OBJECTIVES: The objective of our study was to develop a risk assessment system for HIV-infected patients with comorbid talaromycosis, in order to provide these patients with appropriate, effective and potentially life-saving interventions at an early stage of their illness. PATIENTS/METHODS: This was a multicentre, retrospective cohort study conducted in China. We built a predictive model based on data from 11 hospitals, and a validated model using the data of 1 hospital located in an endemic area. RESULTS: Forward stepwise multivariate statistical calculations indicated that age, aspartate aminotransferase/alanine transaminase ratio and albumin levels, and BUN levels were valid, independent predictors of the risk of death in HIV-infected patients with talaromycosis. Our developed and validated risk scoring system is effective for the identification of HIV-infected patients with talaromycosis at high risk of death at hospital admission (p < .001; AUC = 0.860). In our study, our risk prediction model provided functional and robust discrimination in the validation cohort (p < .001; AUC = 0.793). CONCLUSION: The prognostic scoring system for mortality assessment developed in the present study is an easy-to-use clinical tool designed to accurately assist clinicians in identifying high-risk patients with talaromycosis.

Diagnosis and clinical outcomes of extrapulmonary tuberculosis in antiretroviral therapy programmes in low- and middle-income countries: a multicohort study.

INTRODUCTION: Extrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. Diagnosis can be especially challenging in under-resourced settings. We studied diagnostic modalities and clinical outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV-positive adults in antiretroviral therapy (ART) programmes in low- and middle-income countries (LMIC). METHODS: We collected data from HIV-positive TB patients (≥16 years) in 22 ART programmes participating in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in sub-Saharan Africa, Asia-Pacific, and Caribbean, Central and South America regions between 2012 and 2014. We categorized TB as PTB or EPTB (EPTB included mixed PTB/EPTB). We used multivariable logistic regression to assess associations with clinical outcomes. RESULTS AND DISCUSSION: We analysed 2695 HIV-positive TB patients. Median age was 36 years (interquartile range (IQR) 30 to 43), 1102 were female (41%), and the median CD4 count at TB treatment start was 114 cells/µL (IQR 40 to 248). Overall, 1930 had PTB (72%), and 765 EPTB (28%). Among EPTB patients, the most frequently involved sites were the lymph nodes (24%), pleura (15%), abdomen (11%) and meninges (6%). The majority of PTB (1123 of 1930, 58%) and EPTB (582 of 765, 76%) patients were diagnosed based on clinical criteria. Bacteriological confirmation (using positive smear microscopy, culture, Xpert MTB/RIF, or other nucleic acid amplification tests result) was obtained in 897 of 1557 PTB (52%) and 183 of 438 EPTB (42%) patients. EPTB was not associated with higher mortality compared to PTB (adjusted odd ratio (aOR) 1.0, 95% CI 0.8 to 1.3), but TB meningitis was (aOR 1.9, 95% CI 1.0 to 3.1). Bacteriological confirmation was associated with reduced mortality among PTB patients (aOR 0.7, 95% CI 0.6 to 0.8) and EPTB patients (aOR 0.3 95% CI 0.1 to 0.8) compared to TB patients with a negative test result. CONCLUSIONS: Diagnosis of EPTB and PTB at ART programmes in LMIC was mainly based on clinical criteria. Greater availability and usage of TB diagnostic tests would improve the diagnosis and clinical outcomes of both EPTB and PTB.

The cost of hospital care for HIV patients in Colombia: an insurer's perspective.

The aim of this study was to evaluate the cost derived from the hospitalization of people living with HIV (PLHIV) in Colombia between 2011 and 2015. This is an analysis of the direct cost of PLHIV hospitalization from the perspective of an insurer of the Colombian General Social Security System. The costs were calculated in Colombian pesos and corrected for inflation on the basis of the 2017 Consumer Price Index of the Bank of the Republic of Colombia. It was converted to US dollars at the Market Representative Exchange Rate of the same year. We analyzed 1129 hospitalizations in 612 PLHIV, of which 12% started with a diagnosis of HIV during the same hospitalization, with the majority in the AIDS stage (63%). The median overall cost of hospitalizations was US$1509 (25th and 75th percentiles: US$711-US$3254), being even higher in patients with AIDS and as the CD4 T lymphocyte count decreased. The cost derived from the medical care of PLHIV increases as the clinical control of the disease worsens, and it is a key indicator of the impact of the strategies implemented for the timely identification of the infection and subsequent management of the disease.

Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis.

BACKGROUND: Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda. METHODS: We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/µL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization. RESULTS: In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/µL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted. CONCLUSION: CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective.

Cryptococcal Meningitis Treatment Strategies Affected by the Explosive Cost of Flucytosine in the United States: A Cost-effectiveness Analysis.

BACKGROUND: In the United States, cryptococcal meningitis causes approximately 3400 hospitalizations and approximately 330 deaths annually. The US guidelines recommend treatment with amphotericin B plus flucytosine for at least 2 weeks, followed by fluconazole for a minimum of 8 weeks. Due to generic drug manufacturer monopolization, flucytosine currently costs approximately $2000 per day in the United States, with a 2-week flucytosine treatment course costing approximately $28 000. The daily flucytosine treatment cost in the United Kingdom is approximately $22. Cost-effectiveness analysis was performed to determine the value of flucytosine relative to alternative regimens. METHODS: We estimated the incremental cost-effectiveness ratio (ICER) of 3 cryptococcal induction regimens: (1) amphotericin B deoxycholate for 4 weeks; (2) amphotericin and flucytosine (100 mg/kg/day) for 2 weeks; and (3) amphotericin and fluconazole (800 mg/day) for 2 weeks. Costs of care were calculated using 2015 US prices and the medication costs. Survival estimates were derived from a randomized trial and scaled relative to published US survival data. RESULTS: Cost estimates were $83 227 for amphotericin monotherapy, $75 121 for amphotericin plus flucytosine, and $44 605 for amphotericin plus fluconazole. The ICER of amphotericin plus flucytosine was $23 842 per quality-adjusted life-year. CONCLUSIONS: Flucytosine is currently cost-effective in the United States despite a dramatic increase in price in recent years. Combination therapy with amphotericin and flucytosine is the most attractive treatment strategy for cryptococcal meningitis, though the rising price may be creating access issues that will exacerbate if the trend of profiteering continues.

[Correcting for misclassified HIV/aids deaths in Mexico: Retrospective analysis, 1983-2012]. / Corrección de la mala clasificación de las muertes por sida en México: Análisis retrospectivo de 1983 a 2012.

OBJECTIVE: To identify and reassign misclassified AIDS deaths in Mexico, reconstructing the time series of mortality from 1983 to 2012, by state, sex, age, and affiliation to social security. MATERIALS AND METHODS: 15.5 million deaths from 1979 to 2012 were analyzed. The HIV-AIDS mortality correction was done in three phases: a) those causes directly related to AIDS; b) by miscoded deaths, and c) AIDS deaths hidden in other underlying causes of death. Age-standardized rates of mortality (SMR) were calculated by sex, affiliation to social security, and state. RESULTS: 107 981 AIDS deaths from 1983 to 2012 were accumulated, representing 11% of total deaths observed for the period. The SMR in men for all age groups begins to decline since 1996, while for women the decline started in 2008. A similar picture is observed for the population with / without social security. Heterogeneity is a feature for SMR by state. CONCLUSION: An easily replicable methodology for the correction of mortality from AIDS, which generates relevant information for decision making based on the evidence is presented.

[In-hospital mortality in HIV-infected patients: 10 years after the implementation of universal access to HAART in Mexico]. / Mortalidad hospitalaria en pacientes con infección por VIH: a diez años del acceso universal a TARAA en México.

OBJECTIVE: To establish the characteristics and causes of death of HIV patients who die while hospitalized. MATERIALS AND METHODS: We included HIV+ patients who died during hospitalization, in three hospitals in Mexico City between 2010 and 2013. Sociodemographic and clinical data were collected as well as causes of death. We identified preventable deaths (defined as deaths that occurred in patients with less than six months of HAART, or without HAART, with less than 350 CD4 at diagnosis and/or opportunistic events as the cause of hospitalization). RESULTS: 128 deaths were analyzed. The median of CD4 count was 47 cells/mm³; 18% of the patients ignored their HIV status at the time of hospitalization, 51% had less than six months of HAART, 40.5% had never received HAART before. The main causes of death were AIDS defining events, with 65.6%. We identified 70 preventable deaths (57%). CONCLUSIONS: Despite universal access to HAART, HIV patients in Mexico are still dying of AIDS defining illnesses, an indicator of late diagnosis. It is urgent to implement HIV testing programs to allow earlier diagnosis and make HAART benefit accessible to all.

Association between Highly Active Antiretroviral Therapy and Type of Infectious Respiratory Disease and All-Cause In-Hospital Mortality in Patients with HIV/AIDS: A Case Series.

BACKGROUND: Respiratory manifestations of HIV disease differ globally due to differences in current availability of effective highly active antiretroviral therapy (HAART) programs and epidemiology of infectious diseases. OBJECTIVE: To describe the association between HAART and discharge diagnosis and all-cause in-hospital mortality among hospitalized patients with infectious respiratory disease and HIV/AIDS. MATERIAL AND METHODS: We retrospectively reviewed the records of patients hospitalized at a specialty hospital for respiratory diseases in Mexico City between January 1st, 2010 and December 31st, 2011. We included patients whose discharge diagnosis included HIV or AIDS and at least one infectious respiratory diagnosis. The information source was the clinical chart. We analyzed the association between HAART for 180 days or more and type of respiratory disease using polytomous logistic regression and all-cause hospital mortality by multiple logistic regressions. RESULTS: We studied 308 patients, of whom 206 (66.9%) had been diagnosed with HIV infection before admission to the hospital. The CD4+ lymphocyte median count was 68 cells/mm3 [interquartile range (IQR): 30-150]. Seventy-five (24.4%) cases had received HAART for more than 180 days. Pneumocystis jirovecii pneumonia (PJP) (n = 142), tuberculosis (n = 63), and bacterial community-acquired pneumonia (n = 60) were the most frequent discharge diagnoses. Receiving HAART for more than 180 days was associated with a lower probability of PJP [Adjusted odd ratio (aOR): 0.245, 95% Confidence Interval (CI): 0.08-0.8, p = 0.02], adjusted for sociodemographic and clinical covariates. HAART was independently associated with reduced odds (aOR 0.214, 95% CI 0.06-0.75) of all-cause in-hospital mortality, adjusting for HIV diagnosis previous to hospitalization, age, access to social security, low socioeconomic level, CD4 cell count, viral load, and discharge diagnoses. CONCLUSIONS: HAART for 180 days or more was associated with 79% decrease in all-cause in-hospital mortality and lower frequency of PJP as discharge diagnosis. The prevalence of poorly controlled HIV was high, regardless of whether HIV was diagnosed before or during admission. HIV diagnosis and treatment resources should be improved, and strengthening of HAART program needs to be promoted.

Assessment of duration of staying free from acquiring rehappening opportunistic infections among pre-ART people living with HIV/AIDS between 2008 and 2013.

Introduction. In regional state of the study area, HIV (Human Immunodeficiency Virus) prevalence is 2.2% and opportunistic infections (OIs) occurred in 88.9% of pre-ART (Antiretroviral Therapy) people living with HIV/AIDS (PLWHA). Even though OIs are prevalent in the study area, duration of staying free from acquiring rehappening opportunistic infections and its determinant factors are not studied. Method. The study was conducted in randomly selected 341 adult Pre-ART PLWHA who are included in chronic HIV care. OI free duration was estimated using the actuarial life table and Kaplan Meier survival. Cox proportional-hazard model was used to calculate hazard rate. Result. OIs were rediagnosed in three quarters (75.37%) participants. In each week the probability of getting new recurrence OI was about 15.04 per 1000 person weeks. The median duration of not acquiring OI recurrence was 54 weeks. After adjustment, variables associated with recurrence were employment status, marital status, exposure for prophylaxis and adherence to it, CD4 count, and hemoglobin value. Conclusion. Giving prophylaxis and counseling to adhere it, rise in CD4 and hemoglobin level, and enhancing job opportunities should be given for PLWHA who are on chronic HIV care while continuing the care.

Assessment of the efficacy and safety of pre-emptive anti-cytomegalovirus (CMV) therapy in HIV-infected patients with CMV viraemia.

A number of studies have demonstrated that cytomegalovirus (CMV) viraemia is a strong predictor for CMV end-organ disease (EOD) and death in HIV-infected patients. We assess the efficacy and safety of pre-emptive anti-CMV therapy (PACT) for preventing these events. We performed a retrospective study of all HIV-infected patients seen in our institution who had detectable CMV viraemia in 2007. Seventy-one patients with advanced HIV disease (median CD4 cell count = 61 cells/mm(3)) were studied. Sixteen patients received PACT (mainly valganciclovir). Patients who received PACT had lower CD4 cell counts and higher blood CMV DNA levels. The cumulative incidence of CMV EOD and death at one year was 44% and 21% in patients with and without PACT, respectively (p = 0.013). Both PACT and high blood CMV DNA levels were significantly associated with CMV EOD and death in unadjusted analysis. In adjusted analyses, only blood CMV DNA levels remained significantly associated with the risk of CMV EOD and death, whereas PACT was associated with a non-significant trend towards reduced CMV EOD or death (hazard ratio: 0.25, p = 0.13). Five patients with PACT experienced severe drug-related adverse events. In conclusion, the use of PACT in HIV-infected patients with CMV viraemia could improve outcome but is associated with significant toxicity.

Corrección de la mala clasificación de las muertes por sida en México: Análisis retrospectivo de 1983 a 2012 / Correcting for misclassified HIV/aids deaths in Mexico: Retrospective analysis, 1983-2012

Objetivo. Identificar y reasignar defunciones mal clasificadas por sida en México, y reconstruir la mortalidad 1983-2012, por entidad federativa, sexo, edad y derechohabiencia a la seguridad social. Material y métodos. Se analizaron 15.5 millones de defunciones de 1979 a 2012. La corrección de la mortalidad por sida se hizo en tres fases: a) por causas directamente relacionadas con sida, y b) por muertes mal codificadas; c) muertes por sida ocultas en otras causas. Se calcularon tasas estandarizadas por edad de mortalidad (TEM) por sexo, derechohabiencia a la seguridad social y entidad federativa. Resultados. Se acumularon 107981 muertes por sida entre 1983 y 2012 (11% más del total de muertes observadas). La TEM en hombres, para todos los grupos de edad, empieza a descender desde 1996, mientras que para las mujeres la caída inicia en 2008. Un panorama similar se observa para la población con/sin seguridad social. La heterogeneidad caracteriza la TEM estatal. Conclusión. Se presenta una metodología fácilmente replicable para la corrección de la mortalidad de sida que genera información relevante para la toma de decisiones fundamentada en la evidencia.

Objective. To identify and reassign misclassified AIDS deaths in Mexico, reconstructing the time series of mortality from 1983 to 2012, by state, sex, age, and affiliation to social security. Materials and methods. 15.5 million deaths from 1979 to 2012 were analyzed. The HIV-AIDS mortality correction was done in three phases: a) those causes directly related to AIDS; b) by miscoded deaths, and c) AIDS deaths hidden in other underlying causes of death. Age-standardized rates of mortality (SMR) were calculated by sex, affiliation to social security, and state. Results. 107 981 AIDS deaths from 1983 to 2012 were accumulated, representing 11% of total deaths observed for the period. The SMR in men for all age groups begins to decline since 1996, while for women the decline started in 2008. A similar picture is observed for the population with / without social security. Heterogeneity is a feature for SMR by state. Conclusion. An easily replicable methodology for the correction of mortality from AIDS, which generates relevant information for decision making based on the evidence is presented.

Primary prophylaxis of disseminated histoplasmosis in HIV patients in French Guiana: arguments for cost effectiveness.

Histoplasmosis is the first cause of acquired immunodeficiency syndrome (AIDS) and AIDS-related deaths in French Guiana. Cohort data were used to determine whether primary prophylaxis with 100 mg itraconazole for patients with CD4 counts < 150/mm(3) was cost-effective with different scenarios. For a scenario where 12% of patients died, 60% were aware of their human immunodeficiency virus (HIV) infection and adherence was only 50%, primary prophylaxis would prevent 1 death and 9 cases of histoplasmosis for a cost of 36,792 Euros per averted death, 1,533 per life-year saved, 4,415 Euros per averted case, when only counting the costs of itraconazole prophylaxis. Taking into account the total costs of hospitalization showed that primary prophylaxis would allow a savings of 185,178 Euros per year. Even in a scenario of low adherence, primary prophylaxis would be cost-effective in French Guiana, and presumably in the rest of the Guianas and the Amazon.

Risk factors for mortality among MDR- and XDR-TB patients in a high HIV prevalence setting.

SETTING: Recent studies suggest that the prevalence of drug-resistant tuberculosis (TB) in sub-Saharan Africa may be rising. This is of concern, as human immunodeficiency virus (HIV) co-infection in multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has been associated with exceedingly high mortality rates. OBJECTIVE: To identify risk factors associated with mortality in MDR- and XDR-TB patients co-infected with HIV in South Africa. DESIGN: Case-control study of patients who died of all causes within 2 years of diagnosis with MDR- or XDR-TB. RESULTS: Among 123 MDR-TB patients, 78 (63%) died following diagnosis. CD4 count ≤ 50 (HR 4.64, P = 0.01) and 51-200 cells/mm(3) (HR 4.17, P = 0.008) were the strongest independent risk factors for mortality. Among 139 XDR-TB patients, 111 (80%) died. CD4 count ≤ 50 cells/mm(3) (HR 4.46, P = 0.01) and resistance to all six drugs tested (HR 2.54, P = 0.04) were the principal risk factors. Use of antiretroviral therapy (ART) was protective (HR 0.34, P = 0.009). CONCLUSIONS: Mortality due to MDR- and XDR-TB was associated with greater degree of immunosuppression and drug resistance. Efforts to reduce mortality must focus on preventing the amplification of resistance by strengthening TB treatment programs, as well as reducing the pool of immunosuppressed HIV-infected patients through aggressive HIV testing and ART initiation.

The cost-effectiveness of cotrimoxazole in people with advanced HIV infection initiating antiretroviral therapy in sub-Saharan Africa.

BACKGROUND: In sub-Saharan Africa, high mortality rates have been reported among patients with advanced HIV infection initiating antiretroviral therapy (ART). We evaluated the cost-effectiveness of expanding access to cotrimoxazole (CTX) for persons with HIV in averting mortality during the first 6 months of ART. We also evaluated possible cost savings related to prevention of specific opportunistic infections (OIs). METHODS: We developed a decision-analytic model to estimate the incremental cost, deaths averted, and incremental cost-effectiveness ratio. The model compared 2 scenarios for providing CTX and evaluated potential benefits of increased CTX coverage in reducing deaths and cases of OI. The base case scenario represents an estimated current level of CTX coverage among adults initiating ART in low-income countries (65%). The comparator is 97% coverage (excluding only those with contraindications to CTX). We conducted sensitivity analyses on all parameters in the model. RESULTS: Full coverage reduced deaths from 94 to 72 per 1000 patients, averting 22 deaths during the first 6 months of ART compared with the base case. The incremental cost of moving from base case to full coverage was estimated at $3.29 per person on ART and $146.91 per death averted over 6 months. Additional benefits from averted OI cases would likely be realized as well as savings from averted OI treatment costs. CONCLUSIONS: Our findings suggest that expanding CTX coverage is a cost-effective approach to reducing mortality among patients who present with advanced HIV and initiate ART. The expansion of coverage may also yield benefits for OIs.

Newer drugs and earlier treatment: impact on lifetime cost of care for HIV-infected adults.

OBJECTIVE: To determine the component costs of care to optimize treatment with limited resources. DESIGN: We used the Cost-Effectiveness of Preventing AIDS Complications Model of HIV disease and treatment to project life expectancy and both undiscounted and discounted lifetime costs (2010 €). METHODS: We determined medical resource utilization among HIV-infected adults followed from 1998 to 2005 in northern France. Monthly HIV costs were stratified by CD4 cell count. Costs of CD4, HIV RNA and genotype tests and antiretroviral therapy (ART) were derived from published literature. Model inputs from national data included mean age 38 years, mean initial CD4 cell count 372 cells/µl, ART initiation at CD4 cell counts less than 350 cells/µl, and ART regimen costs ranging from €760 to 2570 per month. RESULTS: The model projected a mean undiscounted life expectancy of 26.5 years and a lifetime undiscounted cost of €535,000/patient (€320,700 discounted); 73% of costs were ART related. When patients presented to care with mean CD4 cell counts of 510 cells/µl and initiated ART at CD4 cell counts less than 500 cells/µl or HIV RNA more than 100,000 copies/ml, life expectancy was 27.4 years and costs increased 1-2%, to €546,700 (€324,500 discounted). When we assumed introducing generic drugs would result in a 50% decline in first-line ART costs, lifetime costs decreased 4-6%, to €514,200 (€302 ,800 discounted). CONCLUSION: As HIV disease is treated earlier with more efficacious drugs, survival and thus costs of care will continue to increase. The availability in high-income countries of widely used antiretroviral drugs in generic form could reduce these costs.

Immune reconstitution inflammatory syndrome in a resource-poor setting.

The immune reconstitution inflammatory syndrome (IRIS) associated with highly active antiretroviral therapy (HAART) was studied in rural Ethiopian HIV-infected patients. Review of 1002 charts in an outpatient clinic was conducted. The median CD4 count was 89 cells/mm(3). Ninety-eight patients were hospitalized after initiation of HAART, of whom 74 were hospitalized for manifestations of IRIS (ie, 7% of patients on HAART). Of the 74 patients hospitalized with IRIS, 27 patients had tuberculosis; 12 patients, cryptococcal meningitis; 7 patients, toxoplasmosis; 6 patients, pneumonia and/or effusion; and 5 patients, Pneumocystis jiroveci pneumonia (PCP). Ten adult patients were admitted with gastroenteritis, heretofore not recognized as a manifestation of IRIS. Eighty-one percent of IRIS patients were hospitalized within 3 months of beginning HAART and 99% by 6 months. Of those hospitalized with IRIS, 4 patients (5%) died while in the hospital (3 with cryptococcal meningitis). Thirty-seven or 50% of those hospitalized with IRIS were lost to medical follow up, thus the mortality rate is likely a gross underestimate of the severity of IRIS. In resource-poor settings where the primary goal is to initiate HAART, IRIS may go unrecognized and have fatal consequences.

Vaccines to prevent pneumonia and improve child survival.

For more than 30 years, vaccines have played an important part in pneumonia prevention. Recent advances have created opportunities for further improving child survival through prevention of childhood pneumonia by vaccination. Maximizing routine immunization with pertussis and measles vaccines, coupled with provision of a second opportunity for measles immunization, has rapidly reduced childhood deaths in low-income countries especially in sub-Saharan Africa. Vaccines against the two leading bacterial causes of child pneumonia deaths, Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus), can further improve child survival by preventing about 1,075,000 child deaths per year. Both Hib and pneumococcal conjugate vaccines have proven safety and effectiveness for prevention of radiologically confirmed pneumonia in children, including in low-income and industrializing countries. Both are recommended by WHO for inclusion in national programmes, and, at sharply tiered prices, these vaccines generally meet international criteria of cost-effectiveness for low-income countries. Vaccines only target selected pneumonia pathogens and are less than 100% effective, so they must be complemented by curative care and other preventative strategies. As part of a comprehensive child survival package, the particular advantages of vaccines include the ability to reach a high proportion of all children, including those who are difficult to reach with curative health services, and the ability to rapidly scale up coverage with new vaccines. In this review, we discuss advances made in optimizing the use of established vaccines and the potential issues related to newer bacterial conjugate vaccines in reducing childhood pneumonia morbidity and mortality.

When to initiate highly active antiretroviral therapy in low-resource settings: the Moroccan experience.

BACKGROUND: The aim of this study was to assess the cost-effectiveness of HIV treatment alternatives - with and without highly active antiretroviral therapy (HAART) - within alternative strata based on the CD4+ T-cell count at the initiation of treatment in a low-resource setting. METHODS: A retrospective observational study was conducted following 286 HIV-positive individuals admitted to the principal teaching hospital in Casablanca, Morocco, between 1995 and 2002. Patients were stratified by CD4+ T-cell count and regression models were fitted to determine risk of opportunistic infection. Data on healthcare resource use were derived from patient records and were evaluated from the hospital perspective. RESULTS: HAART led to a significant reduction in the number of HIV-related opportunistic infections (P<0.0001), extended survival (61.3 versus 55.2 months; P<0.0001) and reduced hospital stays (P<0.0001) in comparison with care in the absence of HAART. When medical care and drug costs were considered together, HAART was more costly than providing treatment for opportunistic infections. The incremental cost-effectiveness ratio was lower than gross domestic product (GDP) per capita for patients starting HAART with a CD4+ T-cell count <200 cells/mm3, but this increased to nearly three times GDP per capita when HAART was initiated at CD4+ T-cell counts above this threshold. CONCLUSIONS: HAART is more cost-effective than treating HIV-related opportunistic infections and, contrary to conclusions drawn in developed countries, HAART is more cost-effective when the CD4+ T-cell count drops to <200 cells/mm3.

[Clinical and laboratory findings in HIV-infected patients at the Jeanne Ebori Foundation in Libreville, Gabon (2002-2005)]. / Bilan clinico-biologique des patients infectés par le VIH à la Fondation Jeanne Ebori de Libreville (2002-2005).

The purpose of this study was to evaluate management of HIV-infected/AIDS patients within the framework of the ACCESS program at Center N 3 over a 4-year period. This retrospective single-center study included HIV-positive patients treated at the Jeanne Ebori Foundation in Libreville, Gabon between January 2002 and December 2005. The active file included 749 patients, i.e., 436 undergoing antiretroviral therapy and 313 with intention to treat. The population consisted mainly of city dwellers. Mean patient age was 38.8 years with a female predominance (sex ratio, 0.8). The highest incidence of infection was observed in the 20- to 30-year age group. Socioeconomic position was low in 63.2 % of patients. Clinical suspicion (67%) was the main reason for testing. In order of frequency, symptoms defined according to the WHO criteria were classified as stage B (33.5 %) and stage C (27.1%). Opportunistic infections were observed in 95% of cases: fungal: 57%, bacterial: 30.7%, and viral: 7.3%. Tritherapy, i.e., 2INTI + 1INNTI (72.9%) and 2INTI+1 IP (17.1%), was used in most cases. Treatment led to clinical improvement with a gradual, steady, and sustained increase in CD4 lymphocyte count. Adverse events were noted including gastrointestinal reactions (16%), neurological manifestations (12%), and general symptoms (12%). Concurrent disturbances in lipid levels and liver function were noted. Overall outcome was positive with a decrease in mortality from 39.2% (M0-M6) to 2.7% (M30-M36). The findings of this study show that improvement in socioeconomic conditions and availability of adequate diagnostic and therapeutic resources at management centers to obtain long-term control of HIV infection are still current issues.