Severe morbidity after antiretroviral (ART) initiation: active surveillance in HIV care programs, the IeDEA West Africa collaboration.

BACKGROUND: The causes of severe morbidity in health facilities implementing Antiretroviral Treatment (ART) programmes are poorly documented in sub-Saharan Africa. We aimed to describe severe morbidity among HIV-infected patients after ART initiation, based on data from an active surveillance system established within a network of specialized care facilities in West African cities. METHODS: Within the International epidemiological Database to Evaluate AIDS (IeDEA)--West Africa collaboration, we conducted a prospective, multicenter data collection that involved two facilities in Abidjan, Côte d'Ivoire and one in Cotonou, Benin. Among HIV-infected adults receiving ART, events were recorded using a standardized form. A simple case-definition of severe morbidity (death, hospitalization, fever>38°5C, Karnofsky index<70%) was used at any patient contact point. Then a physician confirmed and classified the event as WHO stage 3 or 4 according to the WHO clinical classification or as degree 3 or 4 of the ANRS scale. RESULTS: From December 2009 to December 2011, 978 adults (71% women, median age 39 years) presented with 1449 severe events. The main diagnoses were: non-AIDS-defining infections (33%), AIDS-defining illnesses (33%), suspected adverse drug reactions (7%), other illnesses (4%) and syndromic diagnoses (16%). The most common specific diagnoses were: malaria (25%), pneumonia (13%) and tuberculosis (8%). The diagnoses were reported as syndromic in one out of five events recorded during this study. CONCLUSIONS: This study highlights the ongoing importance of conventional infectious diseases among severe morbid events occurring in patients on ART in ambulatory HIV care facilities in West Africa. Meanwhile, additional studies are needed due to the undiagnosed aspect of severe morbidity in substantial proportion.

Impact of risk factors for specific causes of death in the first and subsequent years of antiretroviral therapy among HIV-infected patients.

BACKGROUND: Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART). METHODS: Sixteen cohorts from Europe and North America contributed data on adult patients followed from the start of ART. Procedures for coding causes of death were standardized. Estimated hazard ratios (HRs) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load, and AIDS status, before and after the first year of ART. RESULTS: A total of 4237 of 65 121 (6.5%) patients died (median, 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio, 1.04 per year; 95% confidence interval [CI], 1.0-1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular, and malignancy deaths. Patients with presumed transmission through injection drug use had higher rates of all causes of death, particularly for liver-related causes (HRs compared with men who have sex with men: 18.1 [95% CI, 6.2-52.7] during the first year of ART and 9.1 [95% CI, 5.8-14.2] thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection, and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death. CONCLUSIONS: Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can aid in development of appropriate care for HIV-infected individuals and inform guidelines for risk factor management.

Incidence of serious morbidity in HIV-infected adults on antiretroviral therapy in a West African care centre, 2003-2008.

BACKGROUND: In resource-limited settings, scaling-up antiretroviral treatment (ART) has required the involvement of decentralized health facilities with limited equipment. We estimated the incidence of serious morbidity among HIV-infected adults receiving ART in one of these HIV routine care center in sub-Saharan Africa. METHODS: We conducted a prospective study at the Centre Medical de Suivi des Donneurs de Sang (CMSDS), which is affiliated with the National Centre for Blood Transfusion in Abidjan, Côte d'Ivoire. Adult patients infected with HIV-1 or HIV-1/HIV-2 who initiated ART between January 2003 and December 2008 were eligible for the study. Standardized clinical data were collected at each visit. Serious morbidity was defined as a new episode of malaria, WHO stage 3-4 event, ANRS grade 3-4 adverse event, or any event leading to death or to hospitalization. RESULTS: 1008 adults, 67% women, with a median age of 35 years, and a median pre-ART CD4 count of 186/mm3 started ART and were followed for a median of 17.3 months. The overall incidences of loss to follow-up, death, and attrition were 6.2/100 person-years (PY) [95% CI 5.1-7.2], 2.3/100 PY [95% CI 1.6-2.9], and 8.1/100 PY [95% CI 7.0-9.4], respectively. The incidence of first serious event was 11.5/100 PY overall, 15.9/100 PY within the first year and 8.3/100 PY thereafter. The most frequently documented specific diagnoses were malaria, tuberculosis, bacterial septicemia and bacterial pneumonia. CONCLUSION: Among HIV-infected adults followed in routine conditions in a West African primary care clinic, we recorded a high incidence of serious morbidity during the first year on ART. Providing care centers with diagnostic tools and standardizing data collection are necessary steps to improve the quality of care in primary care facilities in sub-Saharan Africa.

AIDS and non-AIDS morbidity and mortality across the spectrum of CD4 cell counts in HIV-infected adults before starting antiretroviral therapy in Cote d'Ivoire.

BACKGROUND: In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell count-specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)-infected adults with high CD4 cell counts. In sub-Saharan Africa, these CD4 cell count-specific estimates are scarce. METHODS: From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Côte d'Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200 cells/µL once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count-specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum. RESULTS: Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ≥650, 500-649, 350-499, 200-349, 100-199, 50-99, and 0-49 cells/µL CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ≥200 CD4 cells/µL, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200-349 and ≥650 cells/µL, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY). CONCLUSIONS: Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ≥200 cells/µL. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub-Saharan Africa.

All-cause and liver-related mortality in HIV positive subjects compared to the general population: differences by HCV co-infection.

BACKGROUND & AIMS: We aimed at comparing overall and liver-related mortality rates, observed in HIV positive subjects followed-up in the Cohorts of Spanish Network on HIV/AIDS Research stratified by HCV co-infection status, with the expected mortality of the general population of same age and sex in Spain, for the period 1997 - 2008. METHODS: We estimated standardized mortality ratio (SMR) and excess mortality, comparing death rates from our cohort (globally and by HCV co-infection) with death rates from the general population standardized by sex in 5 year-age bands. RESULTS: Overall, 5914 HIV positive subjects were included, 37.3% of which were co-infected with HCV; 231 deaths occurred, 10.4% of which were liver-related. SMR for all causes mortality for the HIV positive subjects was 5.6 (CI 95% 4.9-6.4), 2.4 (1.9-3.1) for HCV negative subjects and 11.5 (9.9-13.4) for HCV positive ones. Having HCV co-infection and AIDS yielded an SMR of 20.8 (16.5-26.1) and having AIDS and being HCV negative had an SMR of 4.8 (3.5-6.7). SMR for liver-related mortality was 1.8 (0.6-5.7) for HCV negative subjects vs. 22.4 (14.6-34.3) for HCV positive ones. Overall, both mortality rates as SMR and excess mortality rates were higher for injecting drug users (IDUs) than men having sex with men (MSM) and heterosexuals, patients with AIDS, with and without cART and for subjects included between 1997 and 2003. CONCLUSIONS: There was an excess of all-cause and liver-related mortality in our cohorts compared with the general population. Furthermore, HCV co-infection in HIV positive patients increased the risk of death for both all causes and liver-related causes.

The Coding Causes of Death in HIV (CoDe) Project: initial results and evaluation of methodology.

BACKGROUND: The Coding Causes of Death in HIV (CoDe) Project aims to deliver a standardized method for coding the underlying cause of death in HIV-positive persons, suitable for clinical trials and epidemiologic studies. METHODS: The project incorporates detailed data collection, a classification system, and a centralized adjudication process performed by 2 independent reviewers. The methodology was tested in the Data Collection on Adverse events of Anti-HIV Drugs Study , and independent reviews of causes of death were compared. Logistic regression models identified factors associated with initial agreement by reviewers on underlying cause of death. RESULTS: A total of 491 reported fatal cases were adjudicated; in only 5% of cases the cause of death remained undetermined after adjudication. Reviewers initially agreed on the underlying cause for 339 (69%) deaths. As compared with deaths due to AIDS-related causes, the odds of agreement were more than 80% lower when deaths were ultimately deemed to be due to non-AIDS-related causes (odds ratio = 0.17 [95% confidence interval = 0.08-0.37]) or undetermined causes (0.11 [0.04-0.36]). The odds of initial agreement were also lower for deaths occurring in subjects with hypertension (0.43 [0.22-0.85]) and depression (0.43 [0.23-0.80]). CONCLUSIONS: The extent and format of data collected in the CoDe Project appear to be sufficient for an informed review, and the proposed coding scheme is adequate for obtaining an underlying cause of death.

Derivation of parameters used in Spectrum for eligibility for antiretroviral therapy and survival on antiretroviral therapy.

BACKGROUND: The Spectrum projection package uses estimates of national HIV incidence, demographic data and other assumptions to describe the consequences of the HIV epidemic in low and middle-income countries. The default parameters used in Spectrum are updated every 2 years as new evidence becomes available to inform the model. This paper reviews the default parameters that define the course of HIV progression among adults and children in Spectrum. METHODS: For adults, data available from published and grey literature and data from the ART-LINC International epidemiologic Database to Evaluate AIDS (IeDEA) collaboration were combined to estimate survival among those who started antiretroviral therapy (ART). For children, a review of published material on survival on ART and survival on ART and cotrimoxazole was used to derive survival probabilities. Historical data on the distribution of CD4 cell counts and CD4 cell percentages by age among children who were not treated (before treatment was available) were used to progress children from seroconversion to different CD4 cell levels. RESULTS: Based on the updated evidence estimated survival among adults aged over 15 years in the first year on ART was 86%, while in subsequent years survival was estimated at 90%. Survival among children during the first year on ART was estimated to be 85% and for subsequent years 93%. DISCUSSION: The revised default parameters based on additional data will make Spectrum estimates more accurate than previous rounds of estimates.

Risk behaviors in volunteer blood donors who seroconverted for HIV, Abidjan, Côte d'Ivoire 1997 to 2005.

BACKGROUND: The residual risk of human immunodeficiency virus (HIV) transmission from blood products in the Abidjan National Blood Transfusion Center was estimated to be 1 in 5780 blood donations over the period 2002 through 2004. We aimed at describing risk behaviors in blood donors who seroconverted for HIV in Abidjan to improve the pre-blood donation selection. STUDY DESIGN AND METHODS: We investigated the behavioral profile of HIV seroconverters assessed before their HIV diagnosis, during the blood donation selection at the blood bank of Abidjan, and compared it to the profile documented after this HIV diagnosis, at enrollment in the PRIMO-CI cohort. Since 1997, enrollment in this cohort is offered to every blood donor whose delay since HIV seroconversion was 36 months or less. RESULTS: Among the 418 blood donors who seroconverted for HIV between 1997 and 2005, 241 were enrolled in the cohort. Median age was 28 years and 63% were men. The median time between the last HIV-negative test and the first positive test was 7 months. Since the last blood donation, 29% of donors reported unprotected sexual intercourse with multiple casual sexual partners, 55% unprotected sexual intercourse with one casual sexual partner, and 36% sharing of nail clippers. During the pre-blood donation questionnaire, 69% of HIV seroconverters had reported unprotected sexual intercourse since the last blood donation (vs. 89% reported after donation), and 7% had had multiple casual sexual partners (vs. 32%). CONCLUSION: Volunteer blood donors who seroconverted for HIV in Abidjan reported a high proportion of unprotected sexual intercourse with casual sexual partners.

Low retention of HIV-infected patients on antiretroviral therapy in 11 clinical centres in West Africa.

OBJECTIVE: To study factors associated with the probability of retention in antiretroviral therapy (ART) programmes in West Africa. METHODS: The International epidemiologic Databases to Evaluate AIDS (IeDEA) in West Africa is a prospective, operational, observational cohort study based on collaboration between 11 cohorts of HIV-infected adult patients in Benin, Côte d'Ivoire, Gambia, Mali and Senegal. All patients aged 16 and older at ART initiation, with documented gender and date of ART initiation, were included. For those with at least 1 day of follow-up, Kaplan-Meier method and Weibull regression model were used to estimate the 12-month probability of retention in care and the associated factors. RESULTS: In this data merger, 14 352 patients (61% female) on ART were included. Median age was 37 (interquartile range (IQR): 31-44 years) and median CD4 count at baseline was 131 cells/mm(3) (IQR: 48-221 cells/mm(3)). The first-line regimen was NNRTI-based for 78% of patients, protease inhibitor-based for 17%, and three NRTIs for 3%. The probability of retention was 0.90 [95% confidence interval (CI): 0.89-0.90] at 3 months, 0.84 (95% CI: 0.83-0.85) at 6 months and 0.76 (95% CI: 0.75-0.77) at 12 months. The probability of retention in care was lower in patients with baseline CD4 count <50 cells/mm(3) [adjusted hazard ratio (aHR) = 1.37; 95% CI: 1.27-1.49; P < 0.0001] (reference CD4 > 200 cells/mm(3), in men (aHR = 1.17; 95% CI: 1.10-1.24; P = 0.0002), in younger patients (<30 years) (aHR = 1.10; 95% CI: 1.03-1.19; P = 0.01) and in patients with low haemoglobinaemia <8 g/dl (aHR = 1.33; 95% CI: 1.21-1.45; P < 0.0001). Availability of funds for systematic tracing was associated with better retention (aHR = 0.29; 95% CI: 0.16-0.55; P = 0.001). CONCLUSIONS: Close follow-up, promoting early access to care and ART and a decentralized system of care may improve the retention in care of HIV-infected patients on ART.

Changes in cancer mortality among HIV-infected patients: the Mortalité 2005 Survey.

BACKGROUND: The goal of the current study was to describe the distribution and characteristics of malignancy related deaths among human immunodeficiency virus (HIV)-infected patients with use of data obtained from a national survey conducted in France in 2005 and to compare with results obtained from a similar survey conducted in 2000. METHOD: The underlying cause of death was documented using a standardized questionnaire fulfilled in French hospital wards and networks that were involved in the treatment of HIV-infected patients. RESULTS: Among the 1042 deaths reported in 2005 (964 were reported in 2000), 344 were cancer related (34%), which represented a significant increase from 2000 (29% of deaths were cancer related) (P=.02); 134 of the cancer-related deaths were AIDS related and 210 were not AIDS related. Among the cancer-related causes of death, the proportion of hepatitis-related cancers (6% in 2000 vs. 11% in 2005) and non-AIDS/hepatitis-related cancers (38% in 2000 vs 50% in 2005) significantly increased from 2000 to 2005 (P=.03 and P=.01, respectively), compared with the proportion of cancer that was AIDS related and adjusting for age and sex. Among cases involving AIDS, the proportion of non-Hodgkin lymphoma-associated deaths did not change statistically significantly between 2000 and 2005 (11% and 10% of deaths, respectively). CONCLUSIONS: In this study, an increasing proportion of lethal non-AIDS-related cancers was demonstrated from 2000 to 2005; meanwhile, the proportion of lethal AIDS-related cancers remained stable among HIV-infected patients. Thus, cancer prophylaxis, early diagnosis, and improved management should be included in the routine long-term follow-up of HIV-infected patients.

Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: The French national Mortalité 2005 study.

BACKGROUND/AIMS: Longer exposure to hepatitis C (HCV) or B virus (HBV) and the increased use of hepatitis treatment might have an impact on liver-related deaths in patients co-infected with the Human Immunodeficiency Virus (HIV). We describe the proportion of liver-related deaths among HIV-infected patients in 2005 compared with 2000. METHODS: In a nationwide survey (341 hospital departments involved in HIV management), all deaths of HIV-infected patients were prospectively reported. Deaths from either cirrhosis, hepatocellular carcinoma or fulminant hepatitis were defined as liver-related deaths. RESULTS: Of the 898 deaths reported in 2005, liver-related causes accounted for 15.4%; this is compared to 13.4% in 2000. Among liver-related deaths, hepatocellular carcinoma increased from 15% to 25% (p=0.04). Among hepatocellular carcinoma-related deaths: in 2000, 10% were HCV-infected; in 2005, 25% were HCV-infected (p=0.03). Half of the HCV-related deaths had been treated for HCV but 98% remained HCV-RNA positive at time of death. The proportion of HBV-related deaths remained stable between 2000 and 2005. CONCLUSIONS: Liver-related deaths, mainly liver cancers, have increased in HIV-infected patients in France despite wide access to HCV treatment. The stability of HBV-related deaths might be explained by the use of dually active antiretroviral drugs in co-infected patients.

Duration from seroconversion to eligibility for antiretroviral therapy and from ART eligibility to death in adult HIV-infected patients from low and middle-income countries: collaborative analysis of prospective studies.

BACKGROUND: Estimation of the number of people in need of antiretroviral therapy (ART) in resource-limited settings requires information on the time from seroconversion to ART eligibility and from ART eligibility to death. OBJECTIVES: To estimate duration from seroconversion to different ART eligibility criteria and from ART eligibility to death in HIV-infected adults in low-income and middle-income countries. METHODS: Participants with documented seroconversion from five cohorts (two cohorts from Uganda, two from Thailand and one from Côte d'Ivoire) were analysed. We used Weibull survival models and Bayesian simulation methods to model true (unobserved) first time of treatment eligibility. We set a consistency constraint so that the mean duration from seroconversion to death was equal to the mean from seroconversion to ART eligibility plus the mean from eligibility to death. RESULTS: We analysed data from 2072 participants, 16 157 person-years of follow-up and 794 deaths. For the criterion CD4 T-lymphocyte count <200 cells x10(6)/l, the median duration from seroconversion to ART eligibility was 6.1 years (95% credibility interval 3.3-10.4) for all studies and 7.6 years (95% credibility interval 3.4-15.2) for all but the Thai cohorts. Corresponding estimates for the time from CD4 T-lymphocyte count <200 cells x10(6)/l to death were 2.1 years (0.7-4.8) and 2.7 years (0.8-8.4). When including all cohorts, the mean time from serconversion to CD4 T-lymphocyte count <200 cells x10(6)/l and from CD4 T-lymphocyte count <200 cells x10(6)/l to death represented 66% (38-87%) and 34% (13-62%), respectively of the total survival time. CONCLUSIONS: The duration of different ART eligibility criteria to death was longer than the estimates used in previous calculations of the number of people needing ART. However, uncertainty in estimates was considerable and heterogeneity across cohorts important.

The effect of depressive symptoms at ART initiation on HIV clinical progression and mortality: implications in clinical practice.

BACKGROUND: Depression is common in HIV-infected patients receiving antiretroviral therapy. However, longitudinal studies addressing the role that depression might play in HIV clinical progression and mortality remain rare. This is especially true for those studies that also consider the possible confounding influence of patient's adherence to treatment. METHODS: The ANRS CO-8 APROCO-COPILOTE cohort study enrolled 1,281 individuals at the initiation of a protease-inhibitor-containing regimen between 1997 and 1999. Adherence, depressive symptoms and other psychosocial factors were measured using self-administered questionnaires. Predictors of progression to AIDS or death were studied using Cox models. RESULTS: Out of 1,028 individuals eligible for the present analysis, 92 individuals either died or had an AIDS-defining event during a median follow up of 54 months. At baseline, 377 individuals (41%) reported depressive symptoms and 124 (12%) reported non-adherence at month 4. Depressive symptoms at baseline were associated with progression (hazard ratio [HR] 2.1; P = 0.001). Despite the association between depressive symptoms and nonadherence, depressive symptoms remained a predictor of clinical progression (adjusted HR [aHR] [95% confidence interval (CI)] 1.6 [1.0-2.5]) after adjustment for several factors: initial non-adherence (aHR [95% CI] 2.0 [1.1-3.6]), having a steady partner (aHR [95% CI] 0.5 [0.3-0.7]), older age (aHR [95% CI] 1.40 [1.12-1.74] per 10-year increment), HIV clinical stage C (aHR [95% CI] 2.5 [1.6-4.0]), plasma HIV RNA > or = 100,000 copies/ml (aHR [95% CI] 1.7 [1.1-2.87]) and more than 8 years since HIV diagnosis (aHR [95% CI] 1.8 [1.1-2.8]). CONCLUSION: Depressive symptoms and non-adherence are independent predictors of HIV clinical progression and mortality. Screening and appropriate treatment of depressive symptoms at antiretroviral treatment initiation should be included in the standard care of HIV-infected patients.

Causes of death among human immunodeficiency virus (HIV)-infected adults in the era of potent antiretroviral therapy: emerging role of hepatitis and cancers, persistent role of AIDS.

BACKGROUND: In the era of highly active antiretroviral therapy (HAART) mortality has decreased substantially among human immunodeficiency virus (HIV)-infected people with access to HAART, but there are concerns regarding co-morbidities and adverse effects of HAART, which may impair vital prognosis. The Mortality 2000 study examined the causes of death in HIV-infected adults at a national level in France in the year 2000. METHODS: All French hospital wards known to be involved in the management of HIV infection were asked to notify prospectively the deaths that occurred in 2000 among HIV-infected adults. The causes of death were documented using a standardized questionnaire. RESULTS: The 185 participating wards notified 964 deaths. The main underlying causes of death were AIDS-related (47%, non-Hodgkin's lymphoma: 23%), viral hepatitis (11%, hepatitis C: 9%, hepatitis B: 2%), cancer not related to AIDS or hepatitis (11%), cardiovascular disease (7%), bacterial infections (6%), suicide (4%), and adverse effect of antiretroviral treatments (1%). Among AIDS-related deaths, HIV infection had been diagnosed recently in 20%. Smoking was recorded in 72% of cancer-related deaths and alcohol consumption in 54% of hepatitis-related deaths. Among non-HIV related deaths between 25 and 64 years, the proportion of infectious diseases (including HCV and HBV-related deaths) was higher in HIV-infected adults than in the general population. CONCLUSIONS: Improved strategies for detecting HIV infection before AIDS-defining complications occur are needed in the era of HAART. The prevention of non-AIDS related cancers, especially lung cancer, the management of non-Hodgkin's lymphoma, and of viral hepatitis are also important priorities.

Impact of discontinuation of initial protease inhibitor therapy on further virological response in a cohort of human immunodeficiency virus-infected patients.

Although discontinuation of antiretroviral drug therapy is common, the impact on outcome in routine clinical practice is unknown. The Antiprotéases Cohorte (APROCO) Cohort Study enrolled 1281 patients at the time they started a protease inhibitor (PI)-containing regimen from 1997 through 1999. After a median duration of follow-up of 20 months, 51% of patients had discontinued their initial PI. Prospectively recorded reasons for discontinuation were intolerance (52% of patients), poor adherence (22%), and failure of therapy (15%). In a multivariate logistic regression analysis, only discontinuation due to poor adherence was associated with a lower frequency of human immunodeficiency virus RNA level in plasma of <500 copies/mL 12 months after initiation of therapy (odds ratio, 0.27 vs. no change; P<.0001); discontinuation due to intolerance was not associated with virological response (odds ratio, 0.89; P=.58). Patients experiencing intolerance should be reassured that changing therapy will probably not be harmful. Multidisciplinary efforts should concentrate on ways to avoid discontinuation of treatment for adherence reasons.

Impact of early versus late adherence to highly active antiretroviral therapy on immuno-virological response: a 3-year follow-up study.

OBJECTIVE: To assess the impact of different patterns of adherence to highly active antiretroviral therapy (HAART), in particular, the relative impact of early and late adherence, on long-term immuno-virological response in HIV-infected individuals started on a protease inhibitor-containing regimen. DESIGN: Clinical, immuno-virological and self-reported adherence data were collected at 4 (M4), 12 (M12), 20 (M20), 28 (M28) and 36 (M36) months after HAART initiation in the French APROCO cohort. METHODS: A standardized self-administered questionnaire classified patients as non-adherent, moderately or highly adherent at each visit. Stable viral suppression at both M28 to M36, and a CD4 cell increase > 200 between M0 and M36 were used as outcome measures. RESULTS: Of the 582 patients followed regularly through M36, 360 patients had complete adherence data. Although 59.2% were highly adherent at M4, only 25.8% maintained consistent high adherence throughout the follow-up. High adherence at M4 was independently associated with both stable viral suppression at M28-M36 [OR (95% CI): 2.8 (1.4-5.5)] and a CD4 cell increase > 200 during the same period [OR (95% CI): 3.9 (1.7-9.7)]. However, 'moderately adherent' patients between M12 and M36 had the same likelihood [OR (95% CI): 1.9 (1.1-3.2)] as patients who were always high adherent [OR (95% CI): 1.9 (1.1-3.2)] of achieving stable viral load suppression, relative to those who reported non-adherence episodes. CONCLUSION: Optimizing adherence in the early months of treatment is crucial to ensure long-term immuno-virological high adherence during follow-up have a less negative impact. Priority should be given to interventions aimed to improve adherence in the early months of HAART.

An example of nonrandom missing data for hepatitis C virus status in a prognostic study among HIV-infected patients.

PURPOSE: To describe information bias due to missing data for hepatitis C (HCV) status in the analysis of factors associated with mortality in HIV-infected patients. METHOD: The prospective APROCO cohort enrolled 1,151 HIV-infected adults at the first initiation of highly active antiretroviral treatment in 1997-1998. Conversely to other characteristics, hepatitis B and C serologic status were recorded retrospectively. RESULTS: In a first dataset, HCV status was missing in 29%. HCV infection was associated with a higher hazard of death (Cox model, hazard ratio [HR]=4.1; 95% confidence interval [95% CI], 1.5-11.3). After more efforts to actively document HCV status, the information remained missing in only 10%. All deceased patients who were secondarily documented were recorded as being HCV negative. In fact, before systematic collection of HCV status, nonstructured additional documentation for all deaths led to spontaneous notification of HCV-positive serology at death and not HCV negative. HCV was no longer associated with the hazard of death (HR=1.2; 95% CI, 0.6-2.7). CONCLUSION: These results underline the need to minimize missing data and to investigate the impact of missing data on the results, although the mechanism of bias is difficult to identify. In addition, these results might shed light on the current debate about the association between HCV and progression of HIV infection.

Disease patterns and causes of death of hospitalized HIV-positive adults in West Africa: a multicountry survey in the antiretroviral treatment era.

OBJECTIVE: We aimed to describe the morbidity and mortality patterns in HIV-positive adults hospitalized in West Africa. METHOD: We conducted a six-month prospective multicentre survey within the IeDEA West Africa collaboration in six adult medical wards of teaching hospitals in Abidjan, Ouagadougou, Cotonou, Dakar and Bamako. From April to October 2010, all newly hospitalized HIV-positive patients were eligible. Baseline and follow-up information until hospital discharge was recorded using standardized forms. Diagnoses were reviewed by a local event validation committee using reference definitions. Factors associated with in-hospital mortality were studied with a logistic regression model. RESULTS: Among 823 hospitalized HIV-positive adults (median age 40 years, 58% women), 24% discovered their HIV infection during the hospitalization, median CD4 count was 75/mm(3) (IQR: 25-177) and 48% had previously received antiretroviral treatment (ART). The underlying causes of hospitalization were AIDS-defining conditions (54%), other infections (32%), other diseases (8%) and non-specific illness (6%). The most frequent diseases diagnosed were: tuberculosis (29%), pneumonia (15%), malaria (10%) and cerebral toxoplasmosis (10%). Overall, 315 (38%) patients died during hospitalization and the underlying cause of death was AIDS (63%), non-AIDS-defining infections (26%), other diseases (7%) and non-specific illness or unknown cause (4%). Among them, the most frequent fatal diseases were: tuberculosis (36%), cerebral toxoplasmosis (10%), cryptococcosis (9%) and sepsis (7%). Older age, clinical WHO stage 3 and 4, low CD4 count, and AIDS-defining infectious diagnoses were associated with hospital fatality. CONCLUSIONS: AIDS-defining conditions, primarily tuberculosis, and bacterial infections were the most frequent causes of hospitalization in HIV-positive adults in West Africa and resulted in high in-hospital fatality. Sustained efforts are needed to integrate care of these disease conditions and optimize earlier diagnosis of HIV infection and initiation of ART.

Reasons for hospitalization in HIV-infected children in West Africa.

INTRODUCTION: Current knowledge on morbidity and mortality in HIV-infected children comes from data collected in specific research programmes, which may offer a different standard of care compared to routine care. We described hospitalization data within a large observational cohort of HIV-infected children in West Africa (IeDEA West Africa collaboration). METHODS: We performed a six-month prospective multicentre survey from April to October 2010 in five HIV-specialized paediatric hospital wards in Ouagadougou, Accra, Cotonou, Dakar and Bamako. Baseline and follow-up data during hospitalization were recorded using a standardized clinical form, and extracted from hospitalization files and local databases. Event validation committees reviewed diagnoses within each centre. HIV-related events were defined according to the WHO definitions. RESULTS: From April to October 2010, 155 HIV-infected children were hospitalized; median age was 3 years [1-8]. Among them, 90 (58%) were confirmed for HIV infection during their stay; 138 (89%) were already receiving cotrimoxazole prophylaxis and 64 children (40%) had initiated antiretroviral therapy (ART). The median length of stay was 13 days (IQR: 7-23); 25 children (16%) died during hospitalization and four (3%) were transferred out. The leading causes of hospitalization were WHO stage 3 opportunistic infections (37%), non-AIDS-defining events (28%), cachexia and other WHO stage 4 events (25%). CONCLUSIONS: Overall, most causes of hospitalizations were HIV related but one hospitalization in three was caused by a non-AIDS-defining event, mostly in children on ART. HIV-related fatality is also high despite the scaling-up of access to ART in resource-limited settings.