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.     

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.     

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/mm³ (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.     

Virological response and resistances over 12 months among HIV‐infected children less than two years receiving first‐line lopinavir/ritonavir‐based antiretroviral therapy in Cote d’Ivoire and Burkina Faso: the MONOD ANRS 12206 cohort

Introduction : Lopinavir/ritonavir‐based antiretroviral therapy (ART) is recommended for all HIV‐infected children less than three years. However, little is known about its field implementation and effectiveness in West Africa. We assessed the 12‐month response to lopinavir/ritonavir‐based antiretroviral therapy in a cohort of West African children treated before the age of two years. Methods : HIV‐1‐infected, ART‐naive except for a prevention of mother‐to‐child transmission (PMTCT), tuberculosis‐free, and less than two years of age children with parent's consent were enrolled in a 12‐month prospective therapeutic cohort with lopinavir/ritonavir ART and cotrimoxazole prophylaxis in Ouagadougou and Abidjan. Virological suppression (VS) at 12 months (viral load [VL] <500 copies/mL) and its correlates were assessed. Result s : Between May 2011 and January 2013, 156 children initiated ART at a median age of 13.9 months (interquartile range: 7.8–18.4); 63% were from Abidjan; 53% were girls; 37% were not exposed to any PMTCT intervention or maternal ART; mother was the main caregiver in 81%; 61% were classified World Health Organization Stage 3 to 4. After 12 months on ART, 11 children had died (7%), 5 were lost‐to‐follow‐up/withdrew (3%), and VS was achieved in 109: 70% of children enrolled and 78% of those followed‐up. When adjusting for country and gender, the access to tap water at home versus none (adjusted odds ratio (aOR): 2.75, 95% confidence interval (CI): 1.09–6.94), the mother as the main caregiver versus the father (aOR: 2.82, 95% CI: 1.03–7.71), and the increase of CD4 percentage greater than 10% between inclusion and 6 months versus <10% (aOR: 2.55, 95% CI: 1.05–6.18) were significantly associated with a higher rate of VS. At 12 months, 28 out of 29 children with VL ≥1000 copies/mL had a resistance genotype test: 21 (75%) had ≥1 antiretroviral (ARV) resistance (61% to lamivudine, 29% to efavirenz, and 4% to zidovudine and lopinavir/ritonavir), of which 11 (52%) existed before ART initiation. Conclusions : Twelve‐month VS rate on lopinavir/ritonavir‐based ART was high, comparable to those in Africa or high‐income countries. The father as the main child caregiver and lack of access to tap water are risk factors for viral failure and justify a special caution to improve adherence in these easy‐to‐identify situations before ART initiation. Public health challenges remain to optimize outcomes in children with earlier ART initiation in West Africa.     

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.     

Barriers and facilitators to linkage to ART in primary care: a qualitative study of patients and providers in Blantyre,Malawi

Introduction

Linkage from HIV testing and counselling (HTC) to initiation of antiretroviral therapy (ART) is suboptimal in many national programmes in sub-Saharan Africa, leading to delayed initiation of ART and increased risk of death. Reasons for failure of linkage are poorly understood.

Methods

Semi-structured qualitative interviews were undertaken with health providers and HIV-positive primary care patients as part of a prospective cohort study at primary health centres in Blantyre, Malawi. Patients successful and unsuccessful in linking to ART were included.

Results

Progression through the HIV care pathway was strongly influenced by socio-cultural norms, particularly around the perceived need to regain respect lost during a period of visibly declining health. Capacity to call upon the support of networks of families, friends and employers was a key determinant of successful progression. Over-busy clinics, non-functioning laboratories and unsuitable tools used for ART eligibility assessment (WHO clinical staging system and centralized CD4 count measurement) were important health systems determinants of drop-out.

Conclusions

Key interventions that could rapidly improve linkage include guarantee of same-day, same-clinic ART eligibility assessments; utilization of the support offered by peer-groups and community health workers; and integration of HTC and ART programmes.     

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.     

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape,South Africa

Introduction

There are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low‐resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa.

Methods

The Pediatric Enhanced Surveillance Study enrolled HIV‐infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result <1000 and VL <50 copies/mL using competing risk estimators (death as competing risk). Multivariable sub‐distributional hazards models examined characteristics associated with VS and VL rebound following suppression among those with a VL >30 days after the VS date.

Results

Of 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12 months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At study enrolment, median weight‐for‐age z‐score (WAZ) was −1.7 (interquartile range (IQR):−3.1 to −0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative incidence of VS <1000 copies/mL at six, twelve and twenty‐four months was 57.6% (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to 87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to 69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to 56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95% CI 67.9 to 83.7) of children six to twelve years (p < 0.001). In multivariable models, children with VL >1 million copies/mL at ART initiation were half as likely to achieve VS <50 copies/mL (adjusted sub‐distributional hazards 0.50; 95% CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50 to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds.

Conclusions

We found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes.

     

Communication between HIV-infected children and their caregivers about HIV medicines: a cross-sectional study in Jinja district,Uganda

Introduction

Knowledge of antiretroviral therapy (ART) among children with HIV depends on open communication with them about their health and medicines. Guidelines assign responsibility for communication to children''s home caregivers. Other research suggests that communication is poor and knowledge about ART is low among children on treatment in low-income countries. This study sought to describe communication about medicine for HIV in quantitative terms from the perspectives of both children and caregivers. Thereafter, it established the factors associated with this communication and with children''s knowledge about their HIV medicines.

Methods

We undertook a cross-sectional survey of a random sample of 394 children with HIV on treatment and their caregivers at nine health facilities in Jinja District, Uganda. We assessed reported frequency and content of communication regarding their medicines as well as knowledge of what the medicines were for. Logistic regression analysis was used to determine the factors associated with communication patterns and children''s knowledge of HIV medicines.

Results

Although 79.6% of the caregivers reported that they explained to the children about the medicines, only half (50.8%) of the children said they knew that they were taking medicines for HIV. Older children aged 15–17 years were less likely to communicate with a caregiver about the HIV medicines in the preceding month (OR 0.5, 95% CI 0.3–0.7, p=0.002). Children aged 11–14 years (OR 6.1, 95% CI 2.8–13.7, p<0.001) and 15–17 years (OR 12.6, 95% CI 4.6–34.3, p<0.001) were more likely to know they were taking medicines for HIV compared to the younger ones. The least common reported topic of discussion between children and caregivers was “what the medicines are for” while “the time to take medicines” was by far the most mentioned by children.

Conclusions

Communication about, and knowledge of, HIV medicines among children with HIV is low. Young age (less than 15 years) was associated with more frequent communication. Caregivers should be supported to communicate diagnosis and treatment to children with HIV. Age-sensitive guidelines about the nature and content of communication should be developed.     

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.     

Improved identification and enrolment into care of HIV-exposed and -infected infants and children following a community health worker intervention in Lilongwe,Malawi

Background

Early identification and entry into care is critical to reducing morbidity and mortality in children with HIV. The objective of this report is to describe the impact of the Tingathe programme, which utilizes community health workers (CHWs) to improve identification and enrolment into care of HIV-exposed and -infected infants and children.

Methods

Three programme phases are described. During the first phase, Mentorship Only (MO) (March 2007–February 2008) on-site clinical mentorship on paediatric HIV care was provided. In the second phase, Tingathe-Basic (March 2008–February 2009), CHWs provided HIV testing and counselling to improve case finding of HIV-exposed and -infected children. In the final phase, Tingathe-PMTCT (prevention of mother-to-child transmission) (March 2009–February 2011), CHWs were also assigned to HIV-positive pregnant women to improve mother-infant retention in care. We reviewed routinely collected programme data from HIV testing registers, patient mastercards and clinic attendance registers from March 2005 to March 2011.

Results

During MO, 42 children (38 HIV-infected and 4 HIV-exposed) were active in care. During Tingathe-Basic, 238 HIV-infected children (HIC) were newly enrolled, a six-fold increase in rate of enrolment from 3.2 to 19.8 per month. The number of HIV-exposed infants (HEI) increased from 4 to 118. During Tingathe-PMTCT, 526 HIC were newly enrolled over 24 months, at a rate of 21.9 patients per month. There was also a seven-fold increase in the average number of exposed infants enrolled per month (9.5–70 patients per month), resulting in 1667 enrolled with a younger median age at enrolment (5.2 vs. 2.5 months; p<0.001).During the Tingathe-Basic and Tingathe-PMTCT periods, CHWs conducted 44,388 rapid HIV tests, 7658 (17.3%) in children aged 18 months to 15 years; 351 (4.6%) tested HIV-positive. Over this time, 1781 HEI were enrolled, with 102 (5.7%) found HIV-infected by positive PCR. Additional HIC entered care through various mechanisms (including positive linkage by CHWs and transfer-ins) such that by February 2011, a total of 866 HIC were receiving care, a 23-fold increase from 2008.

Conclusions

A multipronged approach utilizing CHWs to conduct HIV testing, link HIC into care and provide support to PMTCT mothers can dramatically improve the identification and enrolment into care of HIV-exposed and -infected children.