Mortality In HIV-infected Adults Research Articles

Biomarkers of mortality in adults and adolescents with advanced HIV in sub-Saharan Africa

One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and mortality in participants with advanced HIV randomised to cotrimoxazole or enhanced antimicrobial prophylaxis in the Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial (ISRCTN43622374). Biomarkers were assayed using ELISA and Luminex. Associations between baseline values and all-cause 24-week mortality were analysed using Cox models, and for cause-specific mortality used Fine & Gray models, including prophylaxis randomisation, viral load, CD4, WHO stage, age, BMI, and site as covariates; and weighted according to inverse probability of selection into the substudy. Higher baseline CRP, IFN-γ, IL-6 and IP-10 were associated with higher all-cause mortality; and higher IL-23, IL-2 and RANTES with lower all-cause mortality. Associations varied by cause of death: tuberculosis-associated mortality was most strongly associated with higher CRP and sST2, and cryptococcosis-associated mortality with higher IL-4 and lower IL-8. Changes in I-FABP (p = 0.002), faecal alpha-1 antitrypsin (p = 0.01) and faecal myeloperoxidase (p = 0.005) between baseline and 4 weeks post-ART were greater in those receiving enhanced versus cotrimoxazole prophylaxis. Our findings highlight how the immune milieu shapes outcomes following ART initiation, and how adjunctive antimicrobials can modulate the gut environment in advanced HIV.

A social worker intervention to reduce post-hospital mortality in HIV-infected adults in Tanzania (Daraja): Study protocol for a randomized controlled trial

BackgroundIn sub-Saharan Africa (SSA), hospitalized HIV-infected patients who are discharged home have been shown to experience extremely high mortality rate. Daraja is an individual-level, time-limited, five-session case management intervention aiming to link hospitalized HIV-infected patients to outpatient HIV care upon discharge. MethodsA randomized control trial will aim at evaluating the efficacy of Daraja intervention on reducing mortality in hospitalized HIV-infected patients upon discharge from hospital. The study will recruit 500 hospitalized HIV-infected adults who are ART naïve or defaulted for >7 days from hospitals in Mwanza region, Tanzania. Participants will be enrolled during hospitalization and a baseline assessment will be done. Participants will be randomized to receive either the standard of care HIV linkage, or the Daraja intervention a day before the expected hospital discharge date. The Daraja intervention includes five sessions delivered by a social worker over a 3-month period. All participants will complete follow-up assessment at month 12 and 24. Measures will include 1-year survival, HIV care continuum outcomes (linkage, retention, antiretroviral adherence, and viral suppression), and cost (incremental cost of the intervention and cost per life saved). Quality assurance data will be collected, and the feasibility and acceptability of the intervention will be described. Statistical analysis will assess the effectiveness of the Daraja intervention on improving survival and HIV care continuum outcomes. DiscussionHospitalized HIV-infected patients who are being discharged home have higher mortality due to poor linkage to primary HIV care. The Daraja intervention has the potential to address barriers that prevent successful transition from hospital to primary HIV care.Trial registration: ClinicalTrials.gov, NCT03858998. Registered on 01 March 2019.

Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts.

BackgroundHigh HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were associated with a higher risk of severe morbidity and a faster decline in CD4 count in ART-naive patients. We report the association between HIV-1 DNA and mortality in HIV-infected adults in a trial of early ART in West Africa.MethodsIn the Temprano trial, HIV-infected adults were randomly assigned to start ART immediately or defer ART. After trial termination, HIV-1 DNA was measured in whole blood samples frozen at baseline. We analyzed the association between baseline PBMC HIV-1 DNA and long-term mortality.Findings2019 patients were followed for 9253 patient-years (median 4.9 years). At baseline, the median CD4 count was 462/mm3 [IQR 368–571], the median plasma HIV-1 RNA 4.7 log10 copies/ml [IQR 4.0–5.2], and the median HIV-1 DNA 2.9 log10 copies/million PBMC [IQR 2.5–3.3]. During follow-up, 86 participants died. In univariate analysis, the hazard ratio [HR] of death was 2.67 (95% CI, 1.68–4.22) for patients with HIV-1 DNA ≥3 log10 copies/million PBMC vs. others, and 2.10 (95% CI, 1.38–3.21) for patients with HIV-1 RNA ≥5 log10 copies/ml vs. others. In multivariate Cox regression analysis, HIV-1 DNA levels ≥3 log10 copies/million PBMC were strongly associated mortality (adjusted HR = 2.09, 95% CI 1.24–3.52, p= 0.005) while the association between baseline plasma HIV-1 RNA and mortality was not significant.InterpretationIn these African adults who started ART with high CD4 counts, HIV-1 DNA was a strong independent predictor of death. The HIV reservoir still plays a prognostic role in the early ART era.FundingThis trial was supported by the French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, 12224 and 12253)

Association between statin use, atherosclerosis, and mortality in HIV-infected adults.

While HIV infection is associated with increased cardiovascular risk, benefit from statin is not well established in HIV-infected adults. We assessed whether statins are associated with a decrease in carotid artery intima-media thickness (cIMT) progression and all-cause mortality in HIV-infected adults who are at elevated ASCVD risk and recommended for statins. Carotid IMT was measured at baseline and follow-up in 127 HIV-infected adults who meet ACC/AHA criteria to be on statins. Inverse probability of treatment weighting (IPTW) was used to address selection bias. Multivariable models were used to control for baseline characteristics. 28 subjects (22%) were on statins and 99 subjects (78%) were not. Mean cIMT at baseline was 1.2 mm (SD = 0.34) in statin users and 1.1 mm (SD = 0.34) in non-users, and the multivariable adjusted difference was 0.05mm (95%CI -0.11, 0.21 p = 0.53). After 3.2 years of follow-up, average cIMT progression was similar in statin users and non-users (0.062mm/yr vs. 0.058 mm/yr) and the multivariable adjusted difference over the study period was 0.004 mm/yr (95% CI -0.018, 0.025, p = 0.74). All-cause mortality appeared higher in non-statin users compared with statin users, but the difference was not significant (adjusted HR = 0.74, 95%CI 0.17-3.29, p = 0.70). In a HIV cohort who had elevated ASCVD risk and meet ACC/AHA criteria for statins, treatment with statins was not associated with a reduction in carotid atherosclerosis progression or total mortality. Future studies are needed to further explore the impact of statins on cardiovascular risk in the HIV-infected population.

Severe anaemia complicating HIV in Malawi; Multiple co-existing aetiologies are associated with high mortality.

Severe anaemia is a major cause of morbidity and mortality in HIV-infected adults living in resource-limited countries. Comprehensive data on the aetiology are lacking but are needed to improve outcomes. HIV-infected adults with severe (haemoglobin ≤70g/l) or very severe anaemia (haemoglobin ≤ 50 g/l) were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Fifteen potential causes and associations with anaemia severity and mortality were explored. 199 patients were enrolled: 42.2% had very severe anaemia and 45.7% were on ART. More than two potential causes for anaemia were present in 94% of the patients including iron deficiency (55.3%), underweight (BMI<20: 49.7%), TB infection (41.2%) and unsuppressed HIV infection (viral load >1000 copies/ml) (73.9%). EBV/CMV co-infection (16.5%) was associated with very severe anaemia (OR 2.8 95% CI 1.1-6.9). Overall mortality was high (53%; 100/199) with a median time to death of 17.5 days (IQR 6-55) days. Death was associated with folate deficiency (HR 2.2; 95% CI 1.2-3.8) and end stage renal disease (HR 3.2; 95% CI 1.6-6.2). Mortality among severely anaemic HIV-infected adults is strikingly high. Clinicians should be aware of the urgent need for a multifactorial approach including starting or optimising HIV treatment, considering TB treatment, nutritional support and optimising renal management.

Association of Plasma sVCAM-1 and sCD14 with Mortality in HIV-1 Infected West African Adults with High CD4 Counts

Background: Several biomarkers of inflammation and coagulation were reported to be associated with HIV disease progression in different settings. Here we report the association between eleven biomarkers and medium-term mortality in HIV-infected adults who participated in a trial of early antiretroviral therapy (ART) in West Africa (Temprano ANRS 12136). Methods: In Temprano, ART-naive HIV-infected adults with high CD4 counts were randomly assigned either to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the 30-month trial follow-up were invited to participate in a post-trial phase (PTP). The PTP endpoint was all-cause death. We used multivariate Cox proportional models to analyze the association between baseline plasma biomarkers (IL-1ra, IL-6, sVCAM-1, sCD14, D-dimer, Fibrinogen, IP-10, sCD163, albumin, hsCRP, 16S rDNA) and all-cause death in the Temprano participants randomized to defer ART. Findings: 477 patients (median age 35, 78% women) were randomly assigned to defer starting ART until the WHO criteria were met. At baseline, the median CD4 count was 379 cells/mm3, the median plasma HIV-1 RNA level 4·6 log10 copies/mL and the median PBMC HIV-1 DNA level 3·0 log10 copies per million PBMC. The participants were followed for 2646 person-years (median 5·8 years). In the follow-up, 89% of participants started ART and 30 died. In the multivariate analysis adjusted for the study center, sex, baseline CD4 count, isoniazid preventive therapy, plasma HIV-1 RNA, PBMC HIV-1 DNA and ART, the risk of death was significantly associated with baseline sVCAM-1 (≥ 1458 vs. < 1458: adjusted hazard ratio [aHR] 2·57, 95% CI 1·13-5·82) and sCD14 (≥ 2187 vs. < 2187: aHR 2·79, IQR 1·29-6·02) levels. Interpretation: In these sub-Saharan African adults with high CD4 counts, pre-ART plasma sVCAM-1 and sCD14 levels were independently associated with mortality. Trial Registration: Registered at Clinical Trials.gov (NCT00495651). Funding Statement: French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, ANRS 12224, ANRS 12253). Declaration of Interests: All authors report no conflict of interest. Ethics Approval Statement: The Temprano protocol, which included the post-trial phase, was approved by the Cote d'Ivoire National Ethics Committee for Health Research. All patients gave written informed consent.

Association between Cellular HIV-1 DNA Level and Mortality in HIV-1 Infected African Adults Starting ART with High CD4 Counts

Background: High HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were associated with a higher risk of severe morbidity and a faster decline in CD4 count in ART-naive patients. We report the association between HIV-1 DNA and mortality in HIV-infected adults in a trial of early ART in West Africa. Methods: In the Temprano trial, HIV-infected adults were randomly assigned to start ART immediately or defer ART. After trial termination, HIV-1 DNA was measured in whole blood samples frozen at baseline. We analyzed the association between baseline PBMC HIV-1 DNA and long-term mortality. Results: 2,019 patients were followed for 9,253 patient-years (median 4.9 years). At baseline, the median CD4 count was 462/mm3 [IQR 368-571], the median plasma HIV-1 RNA 4.7 log10 copies/ml [IQR 4.0-5.2], and the median HIV-1 DNA 2.9log10 copies/million PBMC [IQR 2.5-3.3]. During follow-up, 86 participants died. In univariate analysis, the hazard ratio [HR] of death was 2.67 (95% CI, 1.68-4.22) for patients with HIV-1 DNA ≥3 log10 copies/million PBMC vs. others, and 2.10 (95% CI, 1.38-3.21) for patients with HIV-1 RNA ≥5 log10 copies/ml vs. others. In multivariate Cox regression analysis, HIV-1 DNA levels ≥3 log10 copies/million PBMC were strongly associated mortality (adjusted HR = 2.09, 95% CI 1.24-3.52, p = 0.005) while the association between baseline plasma HIV-1 RNA and mortality was not significant. Conclusions: In these African adults who started ART with high CD4 counts, HIV-1 DNA was a strong independent predictor of death. The HIV reservoir still plays a prognostic role in the early ART era. Trial Registration: Clinical Trials.gov (NCT00495651). Funding Statement: This trial was supported by grants from the French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, ANRS 12224, ANRS 12253. Declaration of Interests: All authors report no conflict of interest. Ethics Approval Statement: The Temprano protocol, which included the post-trial phase, was approved by the Cote d'Ivoire National Ethics Committee for Health Research.

Reducing Post-Hospital Mortality in HIV-infected Adults in Tanzania

Reducing Post-Hospital Mortality in HIV-infected Adults in Tanzania

“Treatment is not yet necessary”: delays in seeking access to HIV treatment in Uganda and Zimbabwe

We examined the logic that individuals use to account for delaying HIV testing and/or initiating HIV treatment. Our qualitative study, situated within the REALITY trial (Reduction of EArly mortaLITY in HIV infected adults and children starting antiretroviral therapy), was conducted in Uganda and Zimbabwe in 2015. Forty-eight participants (different age groups, sex and viral load/WHO disease stage) were included. Each participant had 2 interviews (1 after 4 weeks of participation in the trial the other after 12 weeks). If a person could manage presenting symptoms, they felt they had “more time” before starting antiretroviral therapy (ART). Their reluctance to have an HIV test (despite deteriorating health) arose from a belief that they were not “sick”, that treatment was “not yet necessary”. People in our study did not consider themselves as presenting “late”, and treatment was not considered urgent as long as they considered their health to be “good enough”.

Blood pressure and mortality in a prospective cohort of HIV-infected adults in Port-au-Prince, Haiti.

The objective of this study was to determine how baseline blood pressure and incident hypertension related to antiretroviral therapy (ART) initiation, HIV-related inflammation and mortality in HIV-infected adults in a low-income country. We conducted long-term follow-up of HIV-infected adults who had participated in a trial of early vs. delayed initiation of ART in Port-au-Prince, Haiti. Between 2005 and 2008, 816 HIV-infected adults were randomized to early (N = 408) vs. delayed ART (when CD4 cell count <200 cells/μl or AIDS-defining condition; N = 408). Blood pressure was measured every 3 months. Hypertension was diagnosed according to the Joint National Committee (JNC-7) guidelines. Biomarkers of inflammation and coagulation were measured from banked enrolment plasma samples. Survival analyses were performed using Stata 14. The median age at enrolment was 39 years. The median follow-up time was 7.3 years. The hypertension incidence rate was 3.41 per 100 person-years, and was similar in early and delayed ART groups. In multivariable models, independent predictors of incident hypertension were older age, higher BMI and plasma interleukin (IL)-6 levels (adjusted hazard ratio, aHR = 1.23, P < 0.001). Systolic pressure more than 140 mmHg at enrolment was associated with increased mortality (aHR = 2.47, P = 0.03) as was systolic pressure less than 90 mmHg (aHR = 2.25, P = 0.04). Prevalent and incident hypertension were also significantly associated with mortality. In a large prospective study of HIV-infected adults, we found a high incidence of hypertension associated with HIV-related inflammation. Baseline hypertension conferred a more than two-fold increased risk of death. Among HIV-infected adults in low-income countries, hypertension should be considered a serious threat to long-term survival.

Hypertension in HIV-Infected Adults: Novel Pathophysiologic Mechanisms.

Globally, 37 million people are living with the HIV virus.1 Since the year 2000, the number of individuals with access to antiretroviral therapy (ART) has significantly increased from 700,000 to over 16 million.1,2 Wide-spread ART use has halved the HIV-related mortality rate, from an estimated 2 million deaths in 2005 to 1 million in 2016.1,2 During the same time period though, cardiovascular disease mortality rates more than doubled in people living with HIV (PLWH).3 Hypertension, the leading risk factor for mortality worldwide, is a growing problem in HIV-infected adults.4–11 HIV-infected adults on ART have a higher prevalence of hypertension when compared with HIV-uninfected individuals.4–6,12–15 A recent meta-analysis of data from around the globe demonstrated that 35% of all HIV-infected adults on ART have hypertension, compared to an estimated 30% of HIV-uninfected adults.6 Among ART-experienced individuals older than 50 years, more than 50% have hypertension.6 In addition, HIV-infected adults with hypertension have a higher risk of cardiovascular events and all-cause mortality than HIV-uninfected adults with hypertension or HIV-infected adults with normal blood pressure.8,13,16–18 A prospective cohort study of over 80,000 HIV-infected and uninfected American veterans followed over a median six-year period, for example, found that HIV-infected adults with hypertension had a 2-fold higher risk of incident acute myocardial infarction as compared with HIV-uninfected adults with hypertension.17 Although the epidemiologic problem of hypertension in HIV-infected adults is well defined,6,7,9 fewer studies have evaluated the pathophysiologic mechanisms leading to hypertension in PLWH. Traditional cardiovascular risk factors explain some, but not all, of the increased hypertension risk among HIV-infected adults.14,19,20 A number of virologic- and treatment-related factors have been implicated, among them chronic inflammation, immune reconstitution, and lipodystrophy, all of which uniquely influence common downstream pathways such as the sympathetic and renin-angiotensin-aldosterone systems.21–25 Therefore, in this review we explore the mechanisms of hypertension in HIV infection. Understanding the mechanisms of hypertension in HIV-infected adults is important for two reasons. First, increased knowledge of the mechanisms of hypertension in HIV-infected adults will be critical to public health efforts to prevent hypertension, cardiovascular disease and premature mortality in HIV-infected adults. Second, the study of HIV-specific pathophysiology of hypertension may reveal important immunologic and inflammatory mechanisms of hypertension in the general population. Our review is not intended to be a comprehensive analysis of the numerous mechanisms of hypertension. Instead, we have focused on those mechanisms which might be particularly important in HIV-infected adults. An enhanced understanding of these processes may thereby aid in the development of new preventative and therapeutic interventions for hypertension in HIV-infected adults and for the general population.

Documenting and explaining the HIV decline in east Zimbabwe: the Manicaland General Population Cohort

PurposeThe Manicaland cohort was established to provide robust scientific data on HIV prevalence and incidence, patterns of sexual risk behaviour and the demographic impact of HIV in a sub-Saharan African...

Molecular diagnosis of central nervous system opportunistic infections and mortality in HIV-infected adults in Central China

BackgroundCSF PCR is the standard diagnostic technique used in resource-rich settings to detect pathogens of the CNS infection. However, it is not currently used for routine CSF testing in China. Knowledge of CNS opportunistic infections among people living with HIV in China is limited.MethodsIntensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral and fungal etiologies. Pathogen-specific primers were used to detect DNA from cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and John Cunningham virus (JCV) via real-time polymerase chain reaction (PCR).ResultsCryptococcal meningitis accounted for 63.0% (34 of 54) of all causes of meningitis, 13.0% (7/54) for TB, 9.3% (5/54) for Toxoplasma gondii. Of 54 samples sent for viral PCR, 31.5% (17/54) were positive, 12 (22.2%) for CMV, 2 (3.7%) for VZV, 1 (1.9%) for EBV, 1 (1.9%) for HHV-6 and 1 (1.9%) for JCV. No patient was positive for HSV. Pathogen-based treatment and high GCS score tended to have a lower mortality rate, whereas patients with multiple pathogens infection, seizures or intracranial hypertension showed higher odds of death.ConclusionCNS OIs are frequent and multiple pathogens often coexist in CSF. Cryptococcal meningitis is the most prevalent CNS disorders among AIDS. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve the diagnosis of AIDS related OIs in resource-limited developing countries, but the cost-efficacy remains to be further evaluated.

Changing Antiretroviral Eligibility Criteria: Impact on the Number and Proportion of Adults Requiring Treatment in Swaziland.

Objective:Early initiation of antiretroviral treatment (ART) at CD4+ cell count ≥500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment.Design:A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012.Methods:Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4+ cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission.Results:Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4+ count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4+ criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4+ criterion of <500 cells per microliter.Conclusions:A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.

Temporal trends in death causes in adults attending an urban HIV clinic in Uganda: a retrospective chart review

ObjectiveTo study temporal trends of mortality in HIV-infected adults who attended an HIV clinic in Kampala, Uganda, between 2002 and 2012.DesignDescriptive retrospective study.MethodsTwo doctors independently reviewed the clinic database that...

A Clinical Predictor Score for 30-Day Mortality among HIV-Infected Adults Hospitalized with Pneumonia in Uganda.

BackgroundPneumonia is a major cause of mortality among HIV-infected patients. Pneumonia severity scores are promising tools to assist clinicians in predicting patients’ 30-day mortality, but existing scores were developed in populations infected with neither HIV nor tuberculosis (TB) and include laboratory data that may not be available in resource-limited settings. The objective of this study was to develop a score to predict mortality in HIV-infected adults with pneumonia in TB-endemic, resource-limited settings.MethodsWe conducted a secondary analysis of data from a prospective study enrolling HIV-infected adults with cough ≥2 weeks and <6 months and clinically suspected pneumonia admitted to Mulago Hospital in Kampala, Uganda from September 2008 to March 2011. Patients provided two sputum specimens for mycobacteria, and those with Ziehl-Neelsen sputum smears that were negative for mycobacteria underwent bronchoscopy with inspection for Kaposi sarcoma and testing for mycobacteria and fungi, including Pneumocystis jirovecii. A multivariable best subsets regression model was developed, and one point was assigned to each variable in the model to develop a clinical predictor score for 30-day mortality.ResultsOverall, 835 patients were studied (mean age 34 years, 53.4% female, 30-day mortality 18.2%). A four-point clinical predictor score was identified and included heart rate >120 beats/minute, respiratory rate >30 breaths/minute, oxygen saturation <90%, and CD4 cell count <50 cells/mm3. Patients’ 30-day mortality, stratified by score, was: score 0 or 1, 12.6%, score 2 or 3, 23.4%, score 4, 53.9%. For each 1 point change in clinical predictor score, the odds of 30-day mortality increased by 65% (OR 1.65, 95% CI 1.39-1.96, p <0.001).ConclusionsA simple, four-point scoring system can stratify patients by levels of risk for mortality. Rapid identification of higher risk patients combined with provision of timely and appropriate treatment may improve clinical outcomes. This predictor score should be validated in other resource-limited settings.

1595Incidence of Kaposi Sarcoma and Associated Mortality in HIV-infected Adults, Fresno, California, 1998-2012

1595Incidence of Kaposi Sarcoma and Associated Mortality in HIV-infected Adults, Fresno, California, 1998-2012

Causes and Determinants of Mortality in HIV-Infected Adults With Tuberculosis: An Analysis From the CAMELIA ANRS 1295-CIPRA KH001 Randomized Trial

Shortening the interval between antituberculosis treatment onset and initiation of antiretroviral therapy (ART) reduces mortality in severely immunocompromised human immunodeficiency virus (HIV)-infected patients with tuberculosis. A better understanding of causes and determinants of death may lead to new strategies to further enhance survival. We assessed mortality rates, causes of death, and factors of mortality in Cambodian HIV-infected adults with CD4 count ≤200 cells/µL and tuberculosis, randomized to initiate ART either 2 weeks (early ART) or 8 weeks (late ART) after tuberculosis treatment onset in the CAMELIA clinical trial. Six hundred sixty-one patients enrolled contributed to 1366.1 person-years of follow-up; 149 (22.5%) died. There were 8.3 deaths per 100 person-years (95% confidence interval [CI], 6.4-10.7) in the early-ART group and 13.8 deaths per 100 person-years (95% CI, 11.2-16.9) in the late-ART group (P = .002). Tuberculosis was the primary cause of death (28%), followed by other HIV-associated conditions (19%). Factors independently associated with mortality in the first 26 weeks were the age, body mass index, hemoglobin, interrupted or ineffective tuberculosis treatment before identification of drug resistance, disseminated tuberculosis, and nontuberculous mycobacterial disease. After 50 weeks in the trial, the most frequent causes of death were non-HIV related or tuberculosis related, including drug toxicity; factors associated with mortality were late ART, loss to follow-up, and absence of cotrimoxazole prophylaxis. Despite ART introduction, mortality remained high, with tuberculosis as the leading cause of death. Reducing tuberculosis-related mortality remains a challenge in resource-limited settings and requires innovative strategies. Clinical Trials Registration. NCT00226434.

Co-Trimoxazole Prophylaxis Is Associated with Reduced Risk of Incident Tuberculosis in Participants in the Swiss HIV Cohort Study

Co-trimoxazole reduces mortality in HIV-infected adults with tuberculosis (TB), and in vitro data suggest potential antimycobacterial activity of co-trimoxazole. We aimed to evaluate whether prophylaxis with co-trimoxazole is associated with a decreased risk of incident TB in Swiss HIV Cohort Study (SHCS) participants. We determined the incidence of TB per 1,000 person-years from January 1992 to December 2012. Rates were analyzed separately in participants with current or no previous antiretroviral treatment (ART) using Poisson regression adjusted for CD4 cell count, sex, region of origin, injection drug use, and age. A total of 13,431 cohort participants contributed 107,549 person-years of follow-up: 182 patients had incident TB-132 (73%) before and 50 (27%) after ART initiation. The multivariable incidence rate ratios for cumulative co-trimoxazole exposure per year for persons with no previous ART and current ART were 0.70 (95% confidence interval [CI], 0.55 to 0.89) and 0.87 (95% CI, 0.74 to 1.0), respectively. Co-trimoxazole may prevent the development of TB among HIV-positive persons, especially among those with no previous ART.

Causes of death in the human immunodeficiency virus population in Western Jamaica

Background: Monitoring the causes of death in patients with human immunodeficiency virus (HIV) in the era of expanding access to antiretroviral therapy in resource-limited settings has implications as more deaths are reported for reasons other than AIDS. Aims: To determine the causes of mortality in HIV-infected adults in Western Jamaica. Materials and Methods: Patients with HIV infection with a death certificate with a known cause of death between 2005 and 2010 were reviewed. Results: There were 189 patients. Co-morbidities were present in 25.3%. The mean age at death was 42.4 years. Early disease (World Health Organization [WHO] stages 1 or 2) was the presentation in 21.5% while 78.6% presented with advanced disease (WHO stages 3 or 4). The mean CD4 count at diagnosis was 95 cells/mm 3 . In patients presenting with early disease, 14.2% presented with sexually transmitted infections, 22.8% skin manifestations, and 14.2% lymphadenopathy. In patients presenting with late disease, 41.7% had Pneumocystis jirovecii pneumonia (PCP), 18.9% central nervous system (CNS) toxoplasmosis, 11.3% HIV-associated nephropathy, and 5% cryptococcal meningitis. At death, 72.6% were in WHO class 4, and 21.2% class 3. The average CD4 count at death was 75.5 cells/mm 3 . Overall, 55.2% of the patients had received highly active antiretroviral therapy. PCP accounted for 42.9% of deaths, 27.3% had CNS opportunistic infections, HIV nephropathy 16.4%, and 4.6% had malignancies. About 52.3% of patients died within 1 year of diagnosis with HIV, while 68.3% died within 2 years. Conclusion: Patients with HIV are presenting with late disease and dying of conditions that are AIDS-related. Efforts to improve early diagnosis and treatment are urgently needed in Jamaica.