All-cause mortality after antiretroviral therapy initiation in HIV-positive women from Europe, Sub-Saharan Africa and the Americas.

BACKGROUND: Women account for over half of persons living with HIV/AIDS globally. We examined geographic variation in all-cause mortality after antiretroviral therapy (ART) for women living with HIV (WLWH) worldwide. METHODS: We pooled data from WLWH at least 18 years initiating ART 2000-2014 within COHERE (Europe) and IeDEA regions (East Africa, West Africa, South Africa, North America, Latin America/Caribbean). Mortality rates were calculated at 0-3, 3-6, 6-12, 12-24 and 24-48 months after ART, and mortality rate ratios were compared with European rates with piecewise exponential parametric survival models based on Poisson regression. FINDINGS: One hundred ninety thousand, one hundred and seventy-five WLWH (16% Europe, 47% East Africa, 13% West Africa, 19% South Africa, 1% South America, 3% North America and 2% Central America/Caribbean) were included. The highest death rates occurred 0-3 months after ART [1.51 (95% CI 1.25-1.82) per 100 person-years in Europe, 12.45 (11.30-13.73), 14.03 (13.12-15.02) and 9.44 (8.80-10.11) in East, West and South Africa, and 1.53 (0.97-2.43), 7.83 (5.44-11.27) and 17.02 (14.62-19.81) in North, South America and Central America/Caribbean, respectively] and declined thereafter. Mortality in Europe was the lowest, with regional differences greatest in the first 3 months and smaller at longer ART durations [adjusted rate ratios 24-48 months after ART: 3.63 (95% CI 3.04-4.33), 5.61 (4.84-6.51) and 3.47 (2.97-4.06) for East, West and South Africa; 2.86 (2.26-3.62), 2.42 (1.65-3.55) and 2.50 (1.92-3.26) for North, South America and Central America/Caribbean, respectively]. CONCLUSION: Global variations in short-term and long-term mortality among WLWH initiating ART may inform context-specific interventions.

Prognostic Factors of Mortality among Adult Patients on Antiretroviral Therapy in India: A Hospital Based Retrospective Cohort Study.

INTRODUCTION: HIV related deaths still continue to occur in large numbers in spite of good quality drugs being freely available in India. This study was therefore done to assess the prognostic factors of mortality among people living with HIV (PLHIV) on antiretroviral therapy (ART). This would help in planning strategies for further improving their survival. MATERIALS AND METHODS: Record based data from baseline and follow-up visits of a cohort of patients aged above 14 years on ART was retrospectively reviewed over a seven-year period. The Kaplan-Meier models were used to estimate life time survival probability, and Cox proportional hazard regression model was used to determine independent prognostic factors of death, among patients, after initiation of ART. RESULTS: Mean age of the total 285 patients enrolled in this study was 45.8±9.7 years. Mean duration of treatment on ART was 1127±611.8 days. During the follow-up period, 44/285(15.4%) patients died, resulting in incidence density of death rate as 3.12 per 100 person years. Good adherence with treatment was reported by 267(93.7%) patients. Nearly half of the deaths, i.e., 21(47.7%), occurred within three months of them starting ART. The mean survival time after initiation of ART was 2084.0±55.3 days (95% CI is 1975.5-2192.5). The presence of opportunistic infections (OIs) and tuberculosis before and poor/average adherence to ART and alcohol usage after starting ART were independent prognostic factors of mortality among patients. CONCLUSION: Several prognostic factors influencing mortality among adult HIV patients receiving treatment were identified in this study. Screening efforts is essential in early detection and management of OIs among PLHIV. Good counselling and monitoring is recommended to improve adherence and also to prevent alcohol usage after initiation of ART. Such measures would help in further reducing mortality among HIV patients in the settings.

Age Distribution of People Dying of HIV/AIDS that Shifted toward Older Ages by 10 Years in the Past 20 Odd Years.

The frequency of the ages at which HIV/AIDS-related deaths occurred and that of patients detected before or after development of AIDS followed a normal distribution. The median age of HIV/AIDS-related deaths was 40-44 years in 1995-1998 and 50-54 years in 2014-2016, whereas the median age at detection of "HIV" or "AIDS" infection was constantly 25-29 years, implying that the survival time of the HIV/AIDS patients became longer by 10 years in the past 20 odd years. The increased survival time could possibly be attributable to the introduction of HIV/AIDS therapies such as HAART. Importantly, however, during the same period, the life span of the Japanese population was lengthened by nearly 10 years. Under the assumption that HIV/AIDS patients died 20 years after the detection of the infection, the total number of deaths was 1,446 in 1990-2016, which was close to 1,532, the total number of deaths in Vital Statistics during the same period.

Síndrome de reconstitución inmune en un paciente de sida con una tuberculosis diseminada / Immune reconstitution syndrome in an AIDS patient with disseminated tuberculosis

La tuberculosis es un factor de riesgo en los pacientes con sida, ya que una vez iniciado el tratamiento antirretroviral pueden de desarrollar un síndrome de reconstitución inmune, lo que favorecería el deterioro del su estado clínico. Se presenta el caso de un paciente masculino, de 24 años de edad, diagnosticado de sida hace 4 años, y tratamiento irregular con antirretrovirales. Acudió al Hospital Universitario Clínico Quirúrgico "Comandante Faustino Pérez Hernández" con fiebre elevada, acompañado de cuadro general, manifestaciones respiratorias y dolor inguinal derecho. En el examen físico se constató un cuadro adénico generalizado, fue hospitalizado para estudio y tratamiento. Se diagnosticó un síndrome de reconstitución inmune en un paciente de sida con una tuberculosis diseminada, el cual fallece a pesar de la terapéutica impuesta. Este síndrome se caracteriza por una restauración gradual de la inmunidad patógeno-específica, donde el sistema inmune es capaz de reconocer patógenos presentes pero clínicamente ocultos. Se asocia a otros factores de riesgo y puede ser letal; de ahí que el reconocimiento oportuno de los pacientes con alto riesgo de contraerlo, así como un adecuado manejo sobre cuándo iniciar la terapia antirretroviral en cada caso específico, es quizá la única forma de prevenir su desarrollo (AU).

Tuberculosis is a risk factor in patients with AIDS, because once the retroviral treatment begins they can develop an immune reconstitution syndrome that would favor the deterioration of their clinical status. The case of a male patient, aged 24 years is presented. He was diagnosed with AIDS four years ago, and was irregularly treated with antiretroviral. The patient assisted the Clinic-surgical University Hospital "Comandante Faustino Pérez Hernández" with high fever accompanied by general characteristics, respiratory manifestations and right inguinal pain. At the physical examination, generalized adenic characteristics were found. A syndrome of immune reconstitution was diagnosed in an AIDS patient with disseminated tuberculosis; the patient died in spite of the imposed therapy. This syndrome is characterized by the gradual restoration of the pathogen-specific immunity, where the immune system is able of recognizing the pathogens that are present but clinically hidden. It is associated to other risk facts and may be lethal; therefore the timely recognition of the patients at high risk of suffering it, and also an adequate management about when to begin the anti-retroviral therapy in each specific case, is the unique way of preventing its development (AU).

Treatment guidelines and early loss from care for people living with HIV in Cape Town, South Africa: A retrospective cohort study.

BACKGROUND: South Africa has undergone multiple expansions in antiretroviral therapy (ART) eligibility from an initial CD4+ threshold of ≤200 cells/µl to providing ART for all people living with HIV (PLWH) as of September 2016. We evaluated the association of programmatic changes in ART eligibility with loss from care, both prior to ART initiation and within the first 16 weeks of starting treatment, during a period of programmatic expansion to ART treatment at CD4+ ≤ 350 cells/µl. METHODS AND FINDINGS: We performed a retrospective cohort study of 4,025 treatment-eligible, non-pregnant PLWH accessing care in a community health center in Gugulethu Township affiliated with the Desmond Tutu HIV Centre in Cape Town. The median age of participants was 34 years (IQR 28-41 years), almost 62% were female, and the median CD4+ count was 173 cells/µl (IQR 92-254 cells/µl). Participants were stratified into 2 cohorts: an early cohort, enrolled into care at the health center from 1 January 2009 to 31 August 2011, when guidelines mandated that ART initiation required CD4+ ≤ 200 cells/µl, pregnancy, advanced clinical symptoms (World Health Organization [WHO] stage 4), or comorbidity (active tuberculosis); and a later cohort, enrolled into care from 1 September 2011 to 31 December 2013, when the treatment threshold had been expanded to CD4+ ≤ 350 cells/µl. Demographic and clinical factors were compared before and after the policy change using chi-squared tests to identify potentially confounding covariates, and logistic regression models were used to estimate the risk of pre-treatment (pre-ART) loss from care and early loss within the first 16 weeks on treatment, adjusting for age, baseline CD4+, and WHO stage. Compared with participants in the later cohort, participants in the earlier cohort had significantly more advanced disease: median CD4+ 146 cells/µl versus 214 cells/µl (p < 0.001), 61.1% WHO stage 3/4 disease versus 42.8% (p < 0.001), and pre-ART mortality of 34.2% versus 16.7% (p < 0.001). In total, 385 ART-eligible PLWH (9.6%) failed to initiate ART, of whom 25.7% died before ever starting treatment. Of the 3,640 people who started treatment, 58 (1.6%) died within the first 16 weeks in care, and an additional 644 (17.7%) were lost from care within 16 weeks of starting ART. PLWH who did start treatment in the later cohort were significantly more likely to discontinue care in <16 weeks (19.8% versus 15.8%, p = 0.002). After controlling for baseline CD4+, WHO stage, and age, this effect remained significant (adjusted odds ratio [aOR] = 1.30, 95% CI 1.09-1.55). As such, it remains unclear if early attrition from care was due to a "healthy cohort" effect or to overcrowding as programs expanded to accommodate the broader guidelines for treatment. Our findings were limited by a lack of generalizability (given that these data were from a single high-volume site where testing and treatment were available) and an inability to formally investigate the effect of crowding on the main outcome. CONCLUSIONS: Over one-quarter of this ART-eligible cohort did not achieve the long-term benefits of treatment due to early mortality, ART non-initiation, or early ART discontinuation. Those who started treatment in the later cohort appeared to be more likely to discontinue care early, and this outcome appeared to be independent of CD4+ count or WHO stage. Future interventions should focus on those most at risk for early loss from care as programs continue to expand in South Africa.

Predictors of Survival among Adult Ethiopian Patients in the National ART Program at Seven University Teaching Hospitals: A Prospective Cohort Study.

BACKGROUND: In Ethiopia, the publicly funded antiretroviral treatment (ART) program was started in 2005. Two hundred seventy-five thousand patients were enrolled in the national ART program by 2012. However, there is limited data on mortality and predictors of death among adult patients in the ART program. The study aimed to estimate mortality and risk factors for death among adult, ART-naïve patients, started in the national ART program from January 2009 to July 2013. METHODS: Multi-site, prospective, observational cohort study of adult, age > 18 years, ART-naïve patients, started in the national ART program at seven university-affiliated hospitals from January 2009 - July 2013. Kaplan-Meier and Cox regression analyses were used to estimate survival and determine risk factors for death. RESULTS: A total of 976 patients, 594 females (60.9 %), were enrolled into the study. Median age of the cohort was 33years. The median CD4 count at start of ART was 144 cells/µl (interquartile range (IQR) 78-205), and 34.2% (330/965) had CD4 < 100. Sixty-three percent (536/851) had viral load greater than 5 log copies/ml (IQR 4.7-5.7) at base line. One hundred and one deaths were recorded during follow-up period, all-cause mortality rate 10.3%; 5.4 deaths/100 person years of observation, 95% confidence interval 4.4-6.5. Seventy percent of the deaths occurred within six months of starting ART. Cox regression analyses showed that the following measures independently predicted mortality: age >51 years, (Adjusted Hazard Ratio (AHR) 4.01, P=0.003), WHO stages III&IV, (AHR 1.76, p = 0.025), CD4 count, <100, (AHR 2.36, p =0.006), and viral load >5 log copies /ml (CHR 1.71, p = 0.037). CONCLUSION: There is high early on- ART mortality in patients presenting with advanced immunodeficiency. Detecting cases and initiating ART before onset of advanced immunodeficiency might improve survival.

Caracterización de la mortalidad por sida en la provincia Sancti Spíritus. 1986-2011 / Characterization of the mortality by AIDS in the county Sancti Spíritus. 1986-2011

Fundamento: El sida es una de principales causas de muerte en pacientes jóvenes y en la provincia esta enfermedad ha tenido un aumento. Objetivo: Caracterizar la mortalidad por VIH/sida en Sancti Spíritus del 1986 al 2011. Metodología: Se realizó un estudio descriptivo, con análisis de información retrospectiva, que incluyó 90 fallecidos por esta causa, las variables incluyeron edad, sexo, años vividos con diagnóstico de VIH/sida, municipio de residencia, causa del fallecimiento, uso de tratamiento antirretroviral y grado de inmunodepresión. Resultados: Cabaiguán y Sancti Spíritus aportaron el mayor número de fallecidos, el sexo masculino y las edades de 21-40 fueron los más frecuentes, en los periodos de 1996-2000 y 2006-2010; la tendencia fue siempre ascendente. Alrededor de 70 de ellos tenían pocos años de infección por VIH y no utilizaron tratamiento, para un 77.8 %, fallecieron 26 antes de recibir Tratamiento Antirretroviral de Gran Actividad en 1996. Las causas de muerte fundamentales fueron: síndrome de desgaste, neumonía por Pneumocisty jeroveci, neurotoxoplasmosis y cryptosporidiasis Conclusiones: En el período se manifestó tendencia ascendente de la mortalidad en la provincia. El estado de inmunodepresión marcada y alto porcentaje de no uso de Tratamiento Antirretroviral de Gran Actividad que favoreció la aparición de enfermedades oportunistas causantes de las defunciones.

Background: The AIDS is one of main causes of death in young patients and in this county where this illness has had an increase. Objective: To characterize the mortality by HIV/AIDS in Sancti Spíritus from 1986 to 2011. Methodology: It was carried out a descriptive study, with retrospective analysis of the information that included 90 deaths by this cause, the variables included age, sex, lived years with the HIV/AIDS diagnose, residence municipality, causes of the death, use of antiretroviral treatment and immunodepression grade. Results: Cabaiguán and Sancti Spíritus contributed to the biggest number of deceases, the masculine sex and the ages from 21-40 were the most frequent, in the period from 1996-2000 and 2006-2010; the tendency was always upward. Around 70 of them had few years of infection for HIV and they didn't use treatment, from a 77.8%, 26 died before receiving Antiretroviral Treatment of Great Activity in 1996. The fundamental causes of death were: waste syndrome, pneumonia for Pneumocystis jeroveci, neurotoxoplasmosis and cryptosporidiosis. Conclusions: In the period it showed an upward tendency of the mortality in the county. The state of marked immunodepression and high percentage of no use of the Antiretroviral Treatment of Great Activity favored the appearance of opportunist illnesses causing the deceases.

Causes of Death in Hospitalized HIV Patients in the Early Anti-Retroviral Therapy Era.

OBJECTIVE: To establish the cause(s) of death among persons with HIV and AIDS admitted to the Fevers Unit of the Korle-Bu Teaching Hospital (KBTH) in 2007 and to determine whether they were AIDS-related in the era of availability of HAART. METHOD: Retrospective chart review of all deaths that occurred in the year 2007 among inpatients with HIV infection. Cause of Death (COD) was established with post mortem diagnosis, where not available ICD-10 was reviewed independently by two physicians experienced in HIV medicine and a consensus reached as to the most likely COD. RESULTS: In the year under review, 215 (97%) of the 221 adult deaths studied were caused by AIDS and HIV-associated illnesses. Of these, 123 (55.7%) were due to an AIDS-defining illness as described in CDC Category 3 or WHO stage 4. Infections accounted for most of the deaths 158 (71.5%), many of them opportunistic 82 (51.8%). Tuberculosis was the commonest COD. Clinical diagnosis of TB was accurate in 54% of deaths, but was not validated by autopsy in 36% of deaths. There were few deaths (14.5%) in patients on HAART. CONCLUSION: In a developing country like Ghana where HAART was still not fully accessible, AIDS-related events remained the major causes of death in persons living with HIV. Total scale-up of the ART programme with continuous availability of antiretrovirals is therefore imperative to reduce deaths from AIDS and HIV associated illnesses. There is need for interventions for early diagnosis as well as reduction in late presentation and also better diagnostic tools for tuberculosis.

Outcomes of human immunodeficiency virus-infected children after anti-retroviral therapy in Malaysia.

AIMS: To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART). METHODS: Retrospective and prospective data collected through March 2009 from children in four different states in Malaysia enrolled in TREAT Asia's Pediatric HIV Observational Database were analysed. RESULTS: Of 347 children in the cohort, only 278 (80.1%) were commenced on ART. The median CD4 count and median age at baseline prior to ART was 272 cells/µL and 4.2 years (interquartile range (IQR): 1.4, 7.4 years), respectively. The median duration of follow-up was 3.7 years (IQR: 1.8, 6.0) with 32 deaths giving a crude mortality rate of 2.86 per 100 child-years. The mortality rate highest in the first 6 months of ART was 10.62 per 100 child-years and declined to 1.83 per 100 child-years thereafter. On univariate analyses, only baseline median CD4 percentage, weight for age z score, height for age z score and anaemia were significantly associated with mortality. Upon including all four of these predictors into a single multivariate model, only weight for age z score remained statistically significantly predictive of mortality. CONCLUSIONS: Children commenced on ART had high mortality in the first 6 months especially in those with low CD4 percentage, wasting and anaemia. Poor nutritional status is an important independent predictor of mortality in this study. Besides initiating ART therapy, nutritional support and intervention must receive the utmost attention.

Mortality in patients with HIV-1 infection starting antiretroviral therapy in South Africa, Europe, or North America: a collaborative analysis of prospective studies.

BACKGROUND: High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. METHODS AND FINDINGS: Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. CONCLUSIONS: After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary.

The HIV epidemic in Greenland--a slow spreading infection among adult heterosexual Greenlanders.

INTRODUCTION: We aimed to characterise the HIV epidemic in Greenland and to determine incidence, prevalence, mortality rates (MR) and specific causes of deaths. STUDY DESIGN: The study design used was population-based nationwide cohort study. METHODS: We included all patients diagnosed with HIV in Greenland before 2011. Data were obtained from patient files, death certificates and the mandatory reports of HIV cases. Incidence and prevalence were estimated as cases/100,000 adults/year and MR as deaths/1,000 person-years (PYR). MRs were estimated for the pre-HAART (≤1996), early-HAART (1997-2004) and late-HAART (≥2005) periods. Deaths were considered AIDS related, if CD4 count <6 months before death was <200 cells/µL and/or an AIDS-related event occurred <12 months of death. RESULTS: We identified 171 cases of HIV among adult Greenlanders. Of these, 133 (78%) were infected in Greenland, 17 (10%) in Denmark and 21 (12%) in other places. The majority was infected through heterosexual contact [127 (74%)], 30 (18%) through homosexual contact, 3 (2%) through intravenous drug use and 11 (6%) through other or unknown routes of transmission. The median age at HIV diagnosis was 46 years (interquartile range 34-56). The incidence increased from 3.8 before 1989 to 29.7 cases/100,000 adults/year in the late 1990s. The incidence has slowly declined to approximately eight cases/100,000 adults/year. Prevalence increased to a maximum in 2009 (174.9/100,000 inhabitants), and slowly declined since then. A total of 79 have died and 25 have emigrated. MRs were high in the pre- and early-HAART periods, 65.3 [95% confidence intervals (CI) 40.0-106.6] and 87.0 [95% CI 63.5-119.0], and a large fraction of deaths were AIDS related. In the late-HAART period, MR has declined markedly to 53.4 (95% CI 35.8-79.7) with a substantial decline in AIDS-related MR. CONCLUSION: Heterosexual contact is the main route of HIV infection and the patients are diagnosed at a median age of 46. The incidence of newly diagnosed HIV patients has decreased markedly since year 2000. Mortality is high although declining in recent years.

Prevalent and incident tuberculosis are independent risk factors for mortality among patients accessing antiretroviral therapy in South Africa.

BACKGROUND: Patients with prevalent or incident tuberculosis (TB) in antiretroviral treatment (ART) programmes in sub-Saharan Africa have high mortality risk. However, published data are contradictory as to whether TB is a risk factor for mortality that is independent of CD4 cell counts and other patient characteristics. METHODS/FINDINGS: This observational ART cohort study was based in Cape Town, South Africa. Deaths from all causes were ascertained among patients receiving ART for up to 8 years. TB diagnoses and 4-monthly CD4 cell counts were recorded. Mortality rates were calculated and Poisson regression models were used to calculate incidence rate ratios (IRR) and identify risk factors for mortality. Of 1544 patients starting ART, 464 patients had prevalent TB at baseline and 424 developed incident TB during a median of 5.0 years follow-up. Most TB diagnoses (73.6%) were culture-confirmed. A total of 208 (13.5%) patients died during ART and mortality rates were 8.84 deaths/100 person-years during the first year of ART and decreased to 1.14 deaths/100 person-years after 5 years. In multivariate analyses adjusted for baseline and time-updated risk factors, both prevalent and incident TB were independent risk factors for mortality (IRR 1.7 [95% CI, 1.2-2.3] and 2.7 [95% CI, 1.9-3.8], respectively). Adjusted mortality risks were higher in the first 6 months of ART for those with prevalent TB at baseline (IRR 2.33; 95% CI, 1.5-3.5) and within the 6 months following diagnoses of incident TB (IRR 3.8; 95% CI, 2.6-5.7). CONCLUSIONS: Prevalent TB at baseline and incident TB during ART were strongly associated with increased mortality risk. This effect was time-dependent, suggesting that TB and mortality are likely to be causally related and that TB is not simply an epiphenomenon among highly immunocompromised patients. Strategies to rapidly diagnose, treat and prevent TB prior to and during ART urgently need to be implemented.

Impact of previous ART and of ART initiation on outcome of HIV-associated tuberculosis.

BACKGROUND: Combination antiretroviral therapy (cART) has progressively decreased mortality of HIV-associated tuberculosis .To date, however, limited data on tuberculosis treatment outcomes among coinfected patients who are not ART-naive at the time of tuberculosis diagnosis are available. METHODS: A multicenter, observational study enrolled 246 HIV-infected patients diagnosed with tuberculosis, in 96 Italian infectious diseases hospital units, who started tuberculosis treatment. A polytomous logistic regression model was used to identify baseline factors associated with the outcome. A Poisson regression model was used to explain the effect of ART during tuberculosis treatment on mortality, as a time-varying covariate, adjusting for baseline characteristics. RESULTS: Outcomes of tuberculosis treatment were as follows: 130 (52.8%) were successfully treated, 36 (14.6%) patients died in a median time of 2 months (range: 0-16), and 80 (32.6%) had an unsuccessful outcome. Being foreign born or injecting drug users was associated with unsuccessful outcomes. In multivariable Poisson regression, cART during tuberculosis treatment decreased the risk of death, while this risk increased for those who were not ART-naive at tuberculosis diagnosis. CONCLUSIONS: ART during tuberculosis treatment is associated with a substantial reduction of death rate among HIV-infected patients. However, patients who are not ART-naive when they develop tuberculosis remain at elevated risk of death.

Prevalent tuberculosis and mortality among HAART initiators.

The effect of tuberculosis on mortality in people initiating highly-active antiretroviral therapy (HAART) remains unclear; here, we strengthened a previous cohort analysis. Multivariate Cox proportional hazards models were used to assess the association of baseline tuberculosis and time to all-cause mortality among HAART initiators. In reanalysis, treatment for tuberculosis at time of HAART initiation remained unassociated with increased risks of all-cause mortality, with adjusted hazard ratios ranging from 1.00 to 1.09.

Immune reconstitution inflammatory syndrome: incidence and implications for mortality.

OBJECTIVE: To describe incidence of immune reconstitution inflammatory syndrome (IRIS) and its association with mortality in a large multisite US HIV-infected cohort applying an objective, comprehensive definition. DESIGN: We studied 2,610 patients seen during 1996-2007 who initiated or resumed highly active combination antiretroviral therapy (cART) and, during the next 6 months, demonstrated a decline in plasma HIV-RNA viral load of at least 0.5 log(10) copies/ml or an increase of at least 50% in CD4 cell count per microliter. We defined IRIS as the diagnosis of a type B or C condition [as per the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition] or any new mucocutaneous disorder during this same 6-month period. METHODS: We assessed the incidence of IRIS and evaluated risk factors for IRIS using conditional logistic regression and for all-cause mortality using proportional hazards models. RESULTS: We identified 370 cases of IRIS (in 276 patients). Median and nadir CD4 cell counts at cART initiation were 90 and 43 cells/µl, respectively; median viral load was 2.7 log(10) copies/ml. The most common IRIS-defining diagnoses were candidiasis (all forms), cytomegalovirus infection, disseminated Mycobacterium avium intracellulare, Pneumocystis pneumonia, varicella zoster, Kaposi's sarcoma and non-Hodgkin lymphoma. Only one case of Mycobacterium tuberculosis was observed. IRIS was independently associated with CD4 cell count less than 50 cells/µl vs. at least 200 cells/µl [odds ratio (OR) 5.0] and a viral load of at least 5.0 log(10) copies vs. less than 4.0 log(10) copies (OR 2.3). IRIS with a type B-defining or type C-defining diagnosis approximately doubled the risk for all-cause mortality. CONCLUSION: In this large US-based HIV-infected cohort, IRIS occurred in 10.6% of patients who responded to effective ART and contributed to increased mortality.

Causes of death in the HAART era.

PURPOSE OF REVIEW: Compared with vast literature on the clinical, imaging, and in-vivo microbiology aspects of HIV disease, there is less on biopsy pathology and even less on autopsy data. This review focuses on some current clinico-pathological issues, with indications of where there is less certainty than we would like. RECENT FINDINGS: The most important change in causes of death in HIV disease, since the advent of highly active antiretroviral therapy (HAART), is the reduction of classical AIDS-defining opportunistic diseases, with the compensating increase in background comorbidities related to lifestyle, infections including the hepatitis viruses and HHV8, ageing, drug toxicity and immune reconstitution inflammatory syndrome phenomena. In low-income countries, HIV contributes significantly to maternal mortality. SUMMARY: To understand HIV disease better and manage future patients better, we need more tissue clinico-pathological correlation, including quality biopsy and autopsy evaluations.

Risk factors associated with increased mortality among HIV infected children initiating antiretroviral therapy (ART) in South Africa.

OBJECTIVE: To identify demographic and clinical risk factors associated with mortality after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency (HIV) infected children in KwaZulu-Natal, South Africa. METHODS: We performed a retrospective cohort study of 537 children initiating antiretroviral therapy at McCord Hospital in KwaZulu-Natal, South Africa. Data were extracted from electronic medical records and risk factors associated with mortality were assessed using Cox regression analysis. RESULTS: Overall there were 47 deaths from the cohort of 537 children initiating ART with over 991 child-years of follow-up (median 22 months on ART), yielding a mortality rate of 4.7 deaths per 100 child years on ART. Univariate analysis indicated that mortality was significantly associated with lower weight-for-age Z-score (p<0.0001), chronic diarrhea (p = 0.0002), lower hemoglobin (p = 0.002), age <3 years (p = 0.003), and CD4% <10% (p = 0.005). The final multivariable Cox proportional hazards mortality model found age less than 3 years (p = 0.004), CD4 <10% (p = 0.01), chronic diarrhea (p = 0.03), weight-for-age Z-score (<0.0001) and female gender as a covariate varying with time (p = 0.03) all significantly associated with mortality. CONCLUSION: In addition to recognized risk factors such as young age and advanced immunosuppression, we found female gender to be significantly associated with mortality in this pediatric ART cohort. Future studies are needed to determine whether intrinsic biologic differences or socio-cultural factors place female children with HIV at increased risk of death following initiation of ART.