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.     

Disengagement of HIV-positive pregnant and postpartum women from antiretroviral therapy services: a cohort study

Introduction

Recent international guidelines call for expanded access to triple-drug antiretroviral therapy (ART) in HIV-positive women during pregnancy and postpartum. However, high levels of non-adherence and/or disengagement from care may attenuate the benefits of ART for HIV transmission and maternal health. We examined the frequency and predictors of disengagement from care among women initiating ART during pregnancy in Cape Town, South Africa.

Methods

We used routine medical records to follow-up pregnant women initiating ART within prevention of mother-to-child transmission of HIV services in Cape Town, South Africa. Outcomes assessed through six months postpartum were (1) disengagement (no attendance within 56 days of a scheduled visit) and (2) missed visits (returning to care 14–56 days late for a scheduled visit).

Results

A total of 358 women (median age, 28 years; median gestational age, 26 weeks) initiated ART during pregnancy. By six months postpartum, 24% of women (n=86) had missed at least one visit and an additional 32% (n=115) had disengaged from care; together, 49% of women had either missed a visit or had disengaged by six months postpartum. Disengagement was more than twice as frequent postpartum compared to in the antenatal period (6.2 vs. 2.4 per 100 woman-months, respectively; p<0.0001). In a proportional hazards model, later gestational age at initiation (HR: 1.04; 95% CI: 1.00–1.07; p=0.030) and being newly diagnosed with HIV (HR: 1.57; 95% CI: 1.07–2.33; p=0.022) were significant predictors of disengagement after adjusting for patient age, starting CD4 cell count and site of ART initiation.

Conclusions

These results demonstrate that missed visits and disengagement from care occur frequently, particularly post-delivery, among HIV-positive women initiating ART during pregnancy. Women who are newly diagnosed with HIV may be particularly vulnerable and there is an urgent need for interventions both to promote retention overall, as well as targeting women newly diagnosed with HIV during pregnancy.     

A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment

Introduction

There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART).

Methods

Completeness of death recording was estimated using a capture–recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes.

Results

After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3–94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2–35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004–2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults).

Conclusions

South Africa''s civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records.     

Meningitis in HIV-positive patients in sub-Saharan Africa: a review

Introduction

Meningitis is one of the leading causes of death among patients living with HIV in sub-Saharan Africa. There is no widespread tracking of the incidence rates of causative agents among patients living with HIV, yet the aetiologies of meningitis are different than those of the general population.

Methods

We reviewed the scientific literature published in PubMed to determine the incidence rates of meningitis among hospitalized people living with HIV in sub-Saharan Africa and report our findings from seven studies across sub-Saharan Africa.

Results

We found high rates of cryptococcal meningitis (19–68%). Tuberculous meningitis was lower (1–36%), although some centres included possible cases as “other” meningitis; therefore, this may not be a true representation of the total cases. Pyogenic meningitis ranged from 6 to 30% and “other” meningitis ranged from 7 to 28% of all reported cases of meningitis. Mortality rates ranged from 25 to 68%. This review describes the most common aetiologies and provides practical diagnostic, treatment and prevention considerations as they apply to the individual living with HIV in sub-Saharan Africa.

Conclusions

Diagnosis is often limited, and wider availability of accurate and low-cost laboratory diagnostics is desperately needed for prompt diagnosis and initiation of appropriate treatment. Wider acceptance and adoption of available preventative modalities can decrease the incidence of potentially fatal central nervous system infections in African patients living with HIV.     

Missed opportunities of inclusion in a cohort of HIV-infected children to initiate antiretroviral treatment before the age of two in West Africa, 2011 to 2013

Introduction

The World Health Organization (WHO) 2010 guidelines recommended to treat all HIV-infected children less than two years of age. We described the inclusion process and its correlates of HIV-infected children initiated on early antiretroviral therapy (EART) at less than two years of age in Abidjan, Côte d''Ivoire, and Ouagadougou, Burkina Faso.

Methods

All children with HIV-1 infection confirmed with a DNA PCR test of a blood sample, aged less than two years, living at a distance less than two hours from the centres and whose parents (or mother if she was the only legal guardian or the legal caregiver if parents were not alive) agreed to participate in the MONOD ANRS 12206 project were included in a cohort to receive EART based on lopinavir/r. We used logistic regression to identify correlates of inclusion.

Results

Among the 217 children screened and referred to the MONOD centres, 161 (74%) were included and initiated on EART. The main reasons of non-inclusion were fear of father''s refusal (48%), mortality (24%), false-positive HIV infection test (16%) and other ineligibility reasons (12%). Having previously disclosed the child''s and mother''s HIV status to the father (adjusted odds ratio (aOR): 3.20; 95% confidence interval (95% CI): 1.55 to 6.69) and being older than 12 months (aOR: 2.05; 95% CI: 1.02 to 4.12) were correlates of EART initiation. At EART initiation, the median age was 13.5 months, 70% had reached WHO Stage 3/4 and 57% had a severe immune deficiency.

Conclusions

Fear of stigmatization by the father and early competing mortality were the major reasons for missed opportunities of EART initiation. There is an urgent need to involve fathers in the care of their HIV-exposed children and to promote early infant diagnosis to improve their future access to EART and survival.     

Ten‐year attrition and antiretroviral therapy response among HIV‐positive adults: a sex‐based cohort analysis from eight West African countries

IntroductionSex differences have already been reported in sub‐Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow‐up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults.MethodsWe used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no‐follow‐up and 10‐year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively.ResultsA total of 71,283 patients (65.8% women) contributed to 310,007 person‐years of follow‐up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10‐year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow‐up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10‐year attrition throughout the 10‐year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/μL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/μL in their sixth year of follow‐up, whereas men failed to reach it even at the end of the 10‐year follow‐up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%).ConclusionsIn West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex‐adapted are needed for patients in care to monitor attrition, detect early high‐risk groups so that they can stay in care with a durably controlled infection.     

Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV-positive patients

Introduction

Although antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation.

Methods

Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm³ or prior AIDS diagnosis). Predictors for late ART initiation and mortality were determined.

Results

A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46–241) cells/mm³. Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm³ in 2008 to a peak of 302 cells/mm³ after 2011 (p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001). Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27–0.59; p<0.001), sex (male vs. female; OR 1.51, 95% CI 1.18–1.93; p=0.001) and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24–2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77–5.21; p<0.001). Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19–3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31–3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18–7.04; p<0.001) and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.−4.36; p=0.035).

Conclusions

Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented.     

Antiretroviral treatment response of HIV-infected children after prevention of mother-to-child transmission in West Africa

Introduction

We assessed the rate of treatment failure of HIV-infected children after 12 months on antiretroviral treatment (ART) in the Paediatric IeDEA West African Collaboration according to their perinatal exposure to antiretroviral drugs for preventing mother-to-child transmission (PMTCT).

Methods

A retrospective cohort study in children younger than five years at ART initiation between 2004 and 2009 was nested within the pWADA cohort, in Bamako-Mali and Abidjan-Côte d’Ivoire. Data on PMTCT exposure were collected through a direct review of children’s medical records. The 12-month Kaplan-Meier survival without treatment failure (clinical or immunological) was estimated and their baseline factors studied using a Cox model analysis. Clinical failure was defined as the appearance or reappearance of WHO clinical stage 3 or 4 events or any death occurring within the first 12 months of ART. Immunological failure was defined according to the 2006 World Health Organization age-related immunological thresholds for severe immunodeficiency.

Results

Among the 1035 eligible children, PMTCT exposure was only documented for 353 children (34.1%) and remained unknown for 682 (65.9%). Among children with a documented PMTCT exposure, 73 (20.7%) were PMTCT exposed, of whom 61.0% were initiated on a protease inhibitor-based regimen, and 280 (79.3%) were PMTCT unexposed. At 12 months on ART, the survival without treatment failure was 40.6% in the PMTCT-exposed group, 25.2% in the unexposed group and 18.5% in the children with unknown exposure status (p=0.002). In univariate analysis, treatment failure was significantly higher in children unexposed (HR 1.4; 95% CI: 1.0–1.9) and with unknown PMTCT exposure (HR 1.5; 95% CI: 1.2–2.1) rather than children PMTCT-exposed (p=0.01). In the adjusted analysis, treatment failure was not significantly associated with PMTCT exposure (p=0.15) but was associated with immunodeficiency (aHR 1.6; 95% CI: 1.4–1.9; p=0.001), AIDS clinical events (aHR 1.4; 95% CI: 1.0–1.9; p=0.02) at ART initiation and receiving care in Mali compared to Côte d’Ivoire (aHR 1.2; 95% CI: 1.0–1.4; p=0.04).

Conclusions

Despite a low data quality, PMTCT-exposed West African children did not have a poorer 12-month response to ART than others. Immunodeficiency and AIDS events at ART initiation remain the main predictors associated with treatment failure in this operational context.     

Adherence to antiretroviral therapy for HIV in sub‐Saharan Africa and Asia: a comparative analysis of two regional cohorts

Introduction : Our understanding of how to achieve optimal long‐term adherence to antiretroviral therapy (ART) in settings where the burden of HIV disease is highest remains limited. We compared levels and determinants of adherence over time between HIV‐positive persons receiving ART who were enrolled in a bi‐regional cohort in sub‐Saharan Africa and Asia. Methods : This multicentre prospective study of adults starting first‐line ART assessed patient‐reported adherence at follow‐up clinic visits using a 30‐day visual analogue scale. Determinants of suboptimal adherence (<95%) were assessed for six‐month intervals, using generalized estimating equations multivariable logistic regression with multiple imputations. Region of residence (Africa vs. Asia) was assessed as a potential effect modifier. Results : Of 13,001 adherence assessments in 3934 participants during the first 24 months of ART, 6.4% (837) were suboptimal, with 7.3% (619/8484) in the African cohort versus 4.8% (218/4517) in the Asian cohort (p < 0.001). In the African cohort, determinants of suboptimal adherence were male sex (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06–1.53; p = 0.009), younger age (OR 0.8 per 10 year increase; 0.8–0.9; p = 0.003), use of concomitant medication (OR 1.8, 1.0–3.2; p = 0.044) and attending a public facility (OR 1.3, 95% CI 1.1–1.7; p = 0.004). In the Asian cohort, adherence was higher in men who have sex with men (OR for suboptimal adherence 0.6, 95% CI 0.4–0.9; p = 0.029) and lower in injecting drug users (OR for suboptimal adherence 1.6, 95% CI 0.9–2.6; p = 0.075), compared to heterosexuals. Risk of suboptimal adherence decreased with longer ART duration in both regions. Participants in low‐ and lower‐middle‐income countries had a higher risk of suboptimal adherence (OR 1.6, 1.3–2.0; p < 0.001), compared to those in upper‐middle or high‐income countries. Suboptimal adherence was strongly associated with virological failure, in Africa (OR 5.8, 95% CI 4.3–7.7; p < 0.001) and Asia (OR 9.0, 95% CI 5.0–16.2; p < 0.001). Patient‐reported adherence barriers among African participants included scheduling demands, drug stockouts, forgetfulness, sickness or adverse events, stigma or depression, regimen complexity and pill burden. Conclusions : Psychosocial factors and health system resources may explain regional differences. Adherence‐enhancing interventions should address patient‐reported barriers tailored to local settings, prioritizing the first years of ART.     

Long-term usage patterns and clinical outcomes in a community-based differentiated antiretroviral therapy delivery programme in South Africa

Introduction

There is little data on long-term implementation and outcomes for people living with HIV (PLHIV) in differentiated antiretroviral therapy (ART) delivery programmes. We aimed to analyse usage patterns of and associated treatment outcomes in a community ART programme, within the Centralized Chronic Medicines Dispensing and Distribution programme, in South Africa over 3.5 years.

Methods

We performed a retrospective cohort study among PLHIV on first-line ART who were eligible for community ART delivery between October 2016 and March 2019, from 56 urban clinics in KwaZulu-Natal, South Africa. Follow-up ended in March 2020. We measured referral rates and, among those referred, we characterized patterns of community ART usage using group-based trajectory modelling following referral. We used survival analysis to measure the association between community ART usage and loss-to-care (no visit for ≥365 days) and logistic regression to measure the association between community ART usage and viraemia (≥50 copies/ml).

Results

Among the 80,801 patients eligible for community ART, the median age was 36 years, 69.8% were female and the median (interquartile range [IQR]) follow-up time was 22 (13–31) months. In total, 49,961 (61.8%) were referred after a median of 6 (IQR 2–13) months from first eligibility. After referral, time spent in community ART varied; 42% remained consistently in community ART, 15% returned to consistent clinic-based care and the remaining 43% oscillated between community ART and clinic-based care. Following referral, the incidence of loss-to-care was 3.93 (95% confidence interval [CI]: 3.71–4.15) per 100 person-years during periods of community ART usage compared to 5.75 (95% CI: 5.28–6.25) during clinic-based care. In multivariable models, community ART usage was associated with a 36% reduction in the hazards of loss-to-care (adjusted hazard ratio: 0.64 [95% CI: 0.57–0.72]). The proportion of patients who became viraemic after first community ART referral was 5.2% and a 10% increase in time in community ART was associated with a 3% reduction in odds of viraemia (adjusted odds ratio: 0.97 [95% CI: 0.95–0.99]).

Conclusions

Community ART usage patterns vary considerably, while clinical outcomes were good. Promoting consistent community ART usage may reduce clinic burden and the likelihood of patients being lost to care, while sustaining viral suppression.     

Community adherence support improves programme retention in children on antiretroviral treatment: a multicentre cohort study in South Africa

Background

HIV-positive children in low-income settings face many challenges to adherence to antiretroviral treatment (ART) and have increased mortality on treatment compared to children in developed countries. Adult ART programmes have demonstrated benefit from community support to improve treatment outcomes; however, there are no empirical data on the effectiveness of this intervention in children. This study compared clinical, virological and immunological outcomes between children who received and who did not receive community-based adherence support from patient advocates (PAs) in four South African provinces.

Methods

A multicentre cohort study of ART-naïve children was conducted at 47 public ART facilities. Outcome measures were mortality, patient retention, virological suppression and CD4 percentage changes on ART. PAs are lay community health workers who provide adherence and psychosocial support for children''s caregivers, and they undertake home visits to ascertain household challenges potentially impacting on adherence in the child. Corrected mortality estimates were calculated, correcting for deaths amongst those lost to follow-up (LTFU) using probability-weighted Kaplan-Meier and Cox functions.

Results

Three thousand five hundred and sixty three children were included with a median baseline age of 6.3 years and a median baseline CD4 cell percentage of 12.0%. PA-supported children numbered 323 (9.1%). Baseline clinical status variables were equivalent between the two groups. Amongst children LTFU, 38.7% were known to have died. Patient retention after 3 years of ART was 91.5% (95% CI: 86.8% to 94.7%) vs. 85.6% (95% CI: 83.3% to 87.6%) amongst children with and without PAs, respectively (p =0.027). Amongst children aged below 2 years at baseline, retention after 3 years was 92.2% (95% CI: 76.7% to 97.6%) vs. 74.2% (95% CI: 65.4% to 81.0%) in children with and without PAs, respectively (p=0.053). Corrected mortality after 3 years of ART was 3.7% (95% CI: 1.9% to 7.4%) vs. 8.0% (95% CI: 6.5% to 9.8%) amongst children with and without PAs, respectively (p=0.060). In multivariable analyses, children with PAs had reduced probabilities of both attrition and mortality, adjusted hazard ratio (AHR) 0.57 (95% CI: 0.35 to 0.94) and 0.39 (95% CI: 0.15 to 1.04), respectively.

Conclusion

Community-based adherence support is an effective way to improve patient retention amongst children on ART. Expanded implementation of this intervention should be considered in order to reach ART programmatic goals in low-income settings as more children access treatment.     

Impact on ART initiation of point-of-care CD4 testing at HIV diagnosis among HIV-positive youth in Khayelitsha,South Africa

Introduction

Despite the rapid expansion of antiretroviral therapy (ART) programmes in developing countries, pre-treatment losses from care remain a challenge to improving access to treatment. Youth and adolescents have been identified as a particularly vulnerable group, at greater risk of loss from both pre-ART and ART care. Point-of-care (POC) CD4 testing has shown promising results in improving linkage to ART care. In Khayelitsha township, South Africa, POC CD4 testing was implemented at a clinic designated for youth aged 12–25 years. We assessed whether there was an associated reduction in attrition between HIV testing, assessment for eligibility and ART initiation.

Methods

A before-and-after observational study was conducted using routinely collected data. These were collected on patients from May 2010 to April 2011 (Group A) when baseline CD4 count testing was performed in a laboratory and results were returned to the clinic within two weeks. Same-day POC CD4 testing was implemented in June 2011, and data were collected on patients from August 2011 to July 2012 (Group B).

Results

A total of 272 and 304 youth tested HIV-positive in Group A and Group B, respectively. Group B patients were twice as likely to have their ART eligibility assessed compared to Group A patients: 275 (90%) vs. 183 (67%) [relative risk (RR)=2.4, 95% CI: 1.8–3.4, p<0.0001]. More patients in World Health Organization (WHO) Stage 1 disease (85% vs. 69%), with CD4 counts≥350 cells/µL (58% vs. 35%) and more males (13% vs. 7%) were detected in Group B. The proportion of eligible patients who initiated ART was 50% and 44% (p=0.6) in Groups B and A, respectively; and 50% and 43% (p=0.5) when restricted to patients with baseline CD4 count≤250 cells/µL. Time between HIV-testing and ART initiation was reduced from 36 to 28 days (p=0.6).

Discussion

POC CD4 testing significantly improved assessment for ART eligibility. The improvement in the proportion initiating ART and the reduction in time to initiation was not significant due to sample size limitations.

Conclusions

POC CD4 testing reduced attrition between HIV-testing and assessment of ART eligibility. Strategies to improve uptake of ART are needed, possibly by improving patient support for HIV-positive youth immediately after diagnosis.     

The clock is ticking: the rate and timeliness of antiretroviral therapy initiation from the time of treatment eligibility in Kenya

Introduction

Understanding the determinants of timely antiretroviral therapy (ART) initiation is useful for HIV programmes intent on developing models of care that reduce delays in treatment initiation while maintaining a high quality of care. We analysed patient- and facility-level determinants of time to ART initiation among patients who initiated ART in Kenya.

Methods

We collected facility-level information and conducted a retrospective chart review of adults initiating ART between 2007 and 2012 at 51 health facilities in Kenya. We evaluated the association between patient- and facility-level covariates at the time of ART eligibility and time to ART initiation. We also explored the determinants associated with timeliness of ART initiation.

Results

The analysis included 11,942 patients. The median age at the time eligibility was first determined was 37 years (interquartile range [IQR] 31–45). Overall, 75% of patients initiated ART within two months of eligibility. The median CD4 cell count at the time eligibility was first determined rose from 132 (IQR 51–217) in 2007 to 195 (IQR 91–286) in 2011 to 2012 (p<0.001). The cumulative probability of ART initiation among treatment-eligible patients increased over time: 87.1% (95% confidence interval [CI] 85.1–89.0%) in 2007; 96.8% (96.0–97.5%) in 2008; 97.1% (96.3–97.7%) in 2009; 98.5% (98.0 −98.9%) in 2010; and 99.7% (95% CI 99.4 −99.8%) in 2011 to 2012 (p<0.0001). In multivariate analyses, attending a health facility with high ART patient volumes within two months of eligibility was considered the key facility-level determinant of ART initiation (adjusted odds ratio 0.57, 95% CI 0.45–0.72, p<0.001). Patient-level determinants included being eligible for ART in the years subsequent to 2007, advanced World Health Organization clinical stage and low CD4 cell count at the time eligibility was first determined.

Conclusions

Overall, the time between treatment eligibility and ART initiation decreased substantially in Kenya between 2007 and 2012, with uniform gains across different types of health facilities. Our findings highlight the slow increase in CD4 cell counts at the time of ART eligibility over time, indicating that a large number of patients are still beginning ART with advanced HIV disease. Our findings also support the decentralisation of ART services at all health facilities that have the capacity to initiate treatment. Continued evaluation of programme- and country-level data is needed to monitor timeliness of ART initiation as countries continue to expand treatment access.     

TB as a cause of hospitalization and in-hospital mortality among people living with HIV worldwide: a systematic review and meta-analysis

Introduction

Despite significant progress in improving access to antiretroviral therapy over the past decade, substantial numbers of people living with HIV (PLHIV) in all regions continue to experience severe illness and require hospitalization. We undertook a global review assessing the proportion of hospitalizations and in-hospital deaths because of tuberculosis (TB) in PLHIV.

Methods

Seven databases were searched to identify studies reporting causes of hospitalizations among PLHIV from 1 January 2007 to 31 January 2015 irrespective of age, geographical region or language. The proportion of hospitalizations and in-hospital mortality attributable to TB was estimated using random effects meta-analysis.

Results

From an initial screen of 9049 records, 66 studies were identified, providing data on 35,845 adults and 2792 children across 42 countries. Overall, 17.7% (95% CI 16.0 to 20.2%) of all adult hospitalizations were because of TB, making it the leading cause of hospitalization overall; the proportion of adult hospitalizations because of TB exceeded 10% in all regions except the European region. Of all paediatric hospitalizations, 10.8% (95% CI 7.6 to 13.9%) were because of TB. There was insufficient data among children for analysis by region. In-hospital mortality attributable to TB was 24.9% (95% CI 19.0 to 30.8%) among adults and 30.1% (95% CI 11.2 to 48.9%) among children.

Discussion

TB remains a leading cause of hospitalization and in-hospital death among adults and children living with HIV worldwide.     

Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care

Introduction

Combination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment.

Methods

Participants from the Canadian Observational Cohort (CANOC), a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm³ or an AIDS-defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran–Armitage test, and independent correlates of late initiation were identified using logistic regression.

Results

In total, 8942 participants (18% female) of median age 40 years (Q1–Q3 33–47) were included. The median baseline CD4 count increased from 190 cells/mm³ (Q1–Q3 80–320) in 2000 to 360 cells/mm³ (Q1–Q3 220–490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm³ or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm³), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation.

Conclusions

This analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.