High completion of isoniazid preventive therapy among HIV-infected children and adults in Kinshasa, Democratic Republic of Congo.

We assessed isoniazid preventive therapy (IPT) completion and predictors among HIV-infected children and adults in two HIV clinics in Kinshasa, Democratic Republic of Congo. Between 1 September 2012 and 15 June 2013, 546 children (1-15 years) and 1532 adults (>15 years) were initiated on IPT; 86.6% (408/470) of the children and 88.2% (1129/1280) of the adults with an IPT outcome completed their therapy. Patients on antiretroviral therapy at IPT initiation were more likely to complete IPT.

Implementation and Operational Research: Maternal Combination Antiretroviral Therapy Is Associated With Improved Retention of HIV-Exposed Infants in Kinshasa, Democratic Republic of Congo.

BACKGROUND: Programs to prevent mother-to-child HIV transmission are plagued by loss to follow-up (LTFU) of HIV-exposed infants. We assessed if providing combination antiretroviral therapy (cART) to HIV-infected mothers was associated with reduced LTFU of their HIV-exposed infants in Kinshasa, DR Congo. METHODS: We constructed a cohort of mother-infant pairs using routinely collected clinical data. Maternal cART eligibility was based on national guidelines in effect at the time. Infants were considered LTFU after 3 failed tracking attempts after a missed visit or if more than 6 months passed since they were last seen in clinic. Statistical methods accounted for competing risks (eg, death). RESULTS: A total of 1318 infants enrolled at a median age of 2.6 weeks (interquartile range: 2.1-6.9), at which point 24% of mothers were receiving cART. Overall, 5% of infants never returned to care after enrollment and 18% were LTFU by 18 months. The 18-month cumulative incidence of LTFU was 8% among infants whose mothers initiated cART by infant enrollment and 20% among infants whose mothers were not yet on cART. Adjusted for baseline factors, infants whose mothers were not on cART were over twice as likely to be LTFU, with a subdistribution hazard ratio of 2.75 (95% confidence limit: 1.81 to 4.16). The association remained strong regardless of maternal CD4 count at infant enrollment. CONCLUSIONS: Increasing access to cART for pregnant women could improve retention of HIV-exposed infants, thereby increasing the clinical and population-level impacts of prevention of mother-to-child HIV transmission interventions and access to early cART for HIV-infected infants.

Temporal changes in the outcomes of HIV-exposed infants in Kinshasa, Democratic Republic of Congo during a period of rapidly evolving guidelines for care (2007-2013).

OBJECTIVE: Guidelines for prevention of mother-to-child transmission of HIV have developed rapidly, yet little is known about how outcomes of HIV-exposed infants have changed over time. We describe HIV-exposed infant outcomes in Kinshasa, Democratic Republic of Congo, between 2007 and 2013. DESIGN: Cohort study of mother-infant pairs enrolled in family-centered comprehensive HIV care. METHODS: Accounting for competing risks, we estimated the cumulative incidences of early infant diagnosis, HIV transmission, death, loss to follow-up, and combination antiretroviral therapy (cART) initiation for infants enrolled in three periods (2007-2008, 2009-2010, and 2011-2012). RESULTS: 1707 HIV-exposed infants enrolled at a median age of 2.6 weeks. Among infants whose mothers had recently enrolled into HIV care (N = 1411), access to EID by age two months increased from 28% (95% confidence limits [CL]: 24,34%) among infants enrolled in 2007-2008 to 63% (95% CL: 59,68%) among infants enrolled in 2011-2012 (Gray's p-value <0.01). The 18-month cumulative incidence of HIV declined from 16% (95% CL: 11,22%) for infants enrolled in 2007-2008 to 11% (95% CL: 8,16%) for infants enrolled in 2011-2012 (Gray's p-value = 0.19). The 18-month cumulative incidence of death also declined, from 8% (95% CL: 5,12%) to 3% (95% CL: 2,5%) (Gray's p-value = 0.02). LTFU did not improve, with 18-month cumulative incidences of 19% (95% CL: 15,23%) for infants enrolled in 2007-2008 and 22% (95% CL: 18,26%) for infants enrolled in 2011-2012 (Gray's p-value = 0.06). Among HIV-infected infants, the 24-month cumulative incidence of cART increased from 61% (95% CL: 43,75%) to 97% (95% CL: 82,100%) (Gray's p-value <0.01); the median age at cART decreased from 17.9 to 9.3 months. Outcomes were better for infants whose mothers enrolled before pregnancy. CONCLUSIONS: We observed encouraging improvements, but continued efforts are needed.

Predicting mortality in HIV-infected children initiating highly active antiretroviral therapy in a resource-deprived setting.

BACKGROUND: While highly active antiretroviral therapy (HAART) programs have been scaled up across sub-Saharan Africa, no prognostic models for the prediction of mortality risk for children initiating HAART are widely available. Current clinical prediction tools for human immunodeficiency virus (HIV)-infected children are derived from pre-HAART data and therefore cannot predict mortality for children initiating HAART. The purpose of this study was to develop a mortality risk scoring system for HIV-infected children beginning HAART in a resource-deprived setting. METHODS: Observational data from HIV-infected children initiating HAART from December 2004 through March 2012 in Kinshasa, Democratic Republic of Congo, were analyzed. Cox proportional hazards models were constructed to assess associations between demographic and clinical characteristics at the time of HAART initiation and mortality. Each child received a model-based risk score predicting mortality after HAART initiation. RESULTS: By 31 March 2012, 1010 children had started HAART. One hundred three children (10.2%) died at a median of 5.3 months post-HAART initiation, yielding a mortality rate of 3.4 deaths per 100 child-years. The final mortality prediction model included undernutrition, low CD4 count, HIV symptoms, and low total lymphocyte count. These factors were highly predictive of mortality in the study population (C statistic = 0.79) and performed well when applied to the validation population (C statistic = 0.77). CONCLUSIONS: Mortality among children starting HAART in resource-deprived settings can be predicted using a simple scoring system incorporating several readily available factors. Identifying predictors of mortality will help clinicians target modifiable risk factors, such as undernutrition, which are not directly addressed by HAART.

Quantification of CD4 responses to combined antiretroviral therapy over 5 years among HIV-infected children in Kinshasa, Democratic Republic of Congo.

BACKGROUND: The long-term effects of combined antiretroviral therapy (cART) on CD4 percentage in HIV-infected children are incompletely understood, with evidence from resource-deprived areas particularly scarce even though most children with HIV live in such settings. We sought to describe this relationship. METHODS: Observational longitudinal data from cART-naive children enrolled between December 2004 and May 2010 into an HIV care and treatment program in Kinshasa, Democratic Republic of Congo were analyzed. To estimate the effect of cART on CD4 percentage while accounting for time-dependent confounders affected by prior exposure to cART, a marginal structural linear mean model was used. RESULTS: Seven hundred ninety children were active for 2090 person-years and a median of 31 months; 619 (78%) initiated cART. At baseline, 405 children (51%) were in HIV clinical stage 3 or 4; 528 (67%) had advanced or severe immunodeficiency. Compared with no cART, the estimated absolute rise in CD4 percentage was 6.8% [95% confidence interval (CI), 4.7% to 8.9%] after 6 months of cART, 8.6% (95% CI, 7.0% to 10.2%) after 12 months, and 20.5% (95% CI, 16.1% to 24.9%) after 60 months. cART-mediated CD4 percentage gains were slowest but greatest among children with baseline CD4 percentage <15. The cumulative incidence of recovery to "not significant" World Health Organization age-specific immunodeficiency was lower if cART was started when immunodeficiency was severe rather than mild or advanced. CONCLUSIONS: cART increased CD4 percentages among HIV-infected children in a resource-deprived setting, as previously noted among children in the United States. More gradual and protracted recovery in children with lower baseline CD4 percentages supports earlier initiation of pediatric cART.

Barriers to and facilitators of adherence to pediatric antiretroviral therapy in a sub-Saharan setting: insights from a qualitative study.

Despite the need for HIV-positive children to adhere effectively to antiretroviral treatment (ART), a guiding theory for pediatric ART in resource-limited settings is still missing. Understanding factors that influence pediatric ART adherence is critical to developing adequate strategies. In-depth qualitative interviews were undertaken in Kinshasa, Democratic Republic of the Congo, with 20 sets of HIV disclosed and nondisclosed children along with respective caregivers to better characterize barriers, facilitators, and adherence experiences in children taking ART. Commonly cited barriers included lack of food or nutritional support, lack of assistance or supervision for children, lack of assistance for caregivers, and being unable to remember to take medicines on a consistent basis. Facilitators included having a strong caregiver-child relationship and support system along with strategies for maintaining adherence. Similar themes arose within the child-caregiver sets, but were often characterized differently between the two. Children who were aware of their HIV status displayed fewer instances of frustration and conflict concerning taking medicines and within the child-caregiver relationship. Continued study on pediatric ART adherence should account for differing perspectives of children and caregivers, as well as between status disclosed and nondisclosed children. Areas of future intervention should focus on child-caregiver relationships, disclosure of HIV status, and available nutritional and psychosocial support for children and their caregivers.

The effect of highly active antiretroviral therapy on the survival of HIV-infected children in a resource-deprived setting: a cohort study.

BACKGROUND: The effect of highly active antiretroviral therapy (HAART) on the survival of HIV-infected children has not been well quantified. Because most pediatric HIV occurs in low- and middle-income countries, our objective was to provide a first estimate of this effect among children living in a resource-deprived setting. METHODS AND FINDINGS: Observational data from HAART-naïve children enrolled into an HIV care and treatment program in Kinshasa, Democratic Republic of the Congo, between December 2004 and May 2010 were analyzed. We used marginal structural models to estimate the effect of HAART on survival while accounting for time-dependent confounders affected by exposure. At the start of follow-up, the median age of the 790 children was 5.9 y, 528 (66.8%) had advanced or severe immunodeficiency, and 405 (51.3%) were in HIV clinical stage 3 or 4. The children were observed for a median of 31.2 mo and contributed a total of 2,089.8 person-years. Eighty children (10.1%) died, 619 (78.4%) initiated HAART, six (0.8%) transferred to a different care provider, and 76 (9.6%) were lost to follow-up. The mortality rate was 3.2 deaths per 100 person-years (95% confidence interval [CI] 2.4-4.2) during receipt of HAART and 6.0 deaths per 100 person-years (95% CI 4.1-8.6) during receipt of primary HIV care only. The mortality hazard ratio comparing HAART with no HAART from a marginal structural model was 0.25 (95% CI 0.06-0.95). CONCLUSIONS: HAART reduced the hazard of mortality in HIV-infected children in Kinshasa by 75%, an estimate that is similar in magnitude but with lower precision than the reported effect of HAART on survival among children in the United States. Please see later in the article for the Editors' Summary.

Anti-retroviral therapy reduces incident tuberculosis in HIV-infected children.

BACKGROUND: We aimed to estimate the effect of anti-retroviral therapy (ART) on incident tuberculosis (TB) in a cohort of HIV-infected children. METHODS: We analysed data from ART-naïve, TB disease-free children enrolled between December 2004 and April 2008 into an HIV care program in Kinshasa, Democratic Republic of Congo. To estimate the effect of ART on TB incidence while accounting for time-dependent confounders affected by exposure, a Cox proportional hazards marginal structural model was used. RESULTS: 364 children contributed 596.0 person-years of follow-up. At baseline, the median age was 6.9 years; 163 (44.8%) were in HIV clinical stage 3 or 4. During follow-up, 242 (66.5%) children initiated ART and 81 (22.3%) developed TB. At TB diagnosis, 41 (50.6%) were receiving ART. The TB incidence rate in those receiving ART was 10.2 per 100 person-years [95% confidence interval (CI) 7.4-13.9] compared with 20.4 per 100 person-years (95% CI 14.6-27.8) in those receiving only primary HIV care. TB incidence decreased with time on ART, from 18.9 per 100 person-years in the first 6 months to 5.3 per 100 person-years after 12 months of ART. The model-estimated TB hazard ratio for ART was 0.51 (95% CI 0.27-0.94). CONCLUSIONS: For HIV-infected children in TB-endemic areas, ART reduces the hazard of developing TB by 50%.

A visual dosing aid for first-line pediatric antiretroviral treatment in resource-poor settings.

The visual dosing aid (VDA) was developed to facilitate dosing calculations in response to children's; growth and weight during antiretroviral treatment. The theoretical accuracy of the VDA was assessed using anthropometric data from 55 children receiving care in the USA and 324 children in the Democratic Republic of the Congo. The VDA dose was similar to the WHO recommended dose. A potentially significant relative dosing difference of >or=20% occurred in <3% of children for NVP, AZT and d4T, but was observed in 20% for 3TC, overdosing being more frequent. The VDA compared well with generic pediatric fixed dose combination tablets. Results did not differ between sites. The VDA enables accurate dosing of pediatric ART in distinct populations and could facilitate roll-out of pediatric ART in resource-poor settings.

Mortality and associated factors after initiation of pediatric antiretroviral treatment in the Democratic Republic of the Congo.

OBJECTIVE: We aimed to describe factors associated with mortality among children receiving antiretroviral treatment (ART) at a pediatric hospital in Kinshasa, Democratic Republic of the Congo. RESULTS: Two hundred ninety-nine children, <18 years old, were followed for a median of 77 weeks (interquartile range: 61-103) post-ART initiation. Survival probability was 89.6% [95% confidence interval (CI): 85.5-92.6%] at 12 months; 24 of 31 deaths (77.4%) occurred within 2 months of ART initiation. Predictors of mortality in bivariate analysis were >/=2 opportunistic infections before ART initiation, severe immunosuppression as defined by age-specific CD4 count or percentage criteria, hemoglobin <9 g/dL, oral candidiasis, and severe malnutrition. In multivariate analysis, weight for age z-score [hazard ratio (HR): 0.39; 95% CI: 0.27-0.61; P < 0.001] and oral candidiasis (HR: 5.86; 95% CI: 2.34-14.65; P = 0.0002) were independent predictors of mortality. Suspected septic shock was the most common cause of death (n = 12/31, 38.7%). CONCLUSIONS: Children receiving ART in this resource-poor setting were at the highest risk of dying in the first 2 months of ART, particularly when they presented with malnutrition or oral candidiasis. Optimal timing of ART initiation during nutritional rehabilitation should be determined. Promotion of early care seeking, strengthened health care, and prevention services are important to further improve outcome of pediatric ART in resource-poor settings.

Computed CD4 percentage as a low-cost method for determining pediatric antiretroviral treatment eligibility.

BACKGROUND: The performance of the WHO recommendations for pediatric antiretroviral treatment (ART) in resource poor settings is insufficiently documented in routine care. METHODS: We compared clinical and immunological criteria in 366 children aged 0 to 12 years in Kinshasa and evaluated a simple computation to estimate CD4 percent, based on CD4 count, total white blood cell count and percentage lymphocytes. Kappa (kappa) statistic was used to evaluate eligibility criteria and linear regression to determine trends of CD4 percent, count and total lymphocyte count (TLC). RESULTS: Agreement between clinical and immunological eligibility criteria was poor (kappa = 0.26). One third of children clinically eligible for ART were ineligible using immunological criteria; one third of children immunologically eligible were ineligible using clinical criteria. Among children presenting in WHO stage I or II, 54 (32%) were eligible according to immunological criteria. Agreement with CD4 percent was poor for TLC (kappa = 0.04), fair for total CD4 count (kappa = 0.39) and substantial for CD4 percent computational estimate (kappa = 0.71). Among 5 to 12 years old children, total CD4 count was higher in younger age groups (-32 cells/mm3 per year older), CD4 percent was similar across age groups. CONCLUSION: Age-specific thresholds for CD4 percent optimally determine pediatric ART eligibility. The use of CD4 percent computational estimate may increase ART access in settings with limited access to CD4 percent assays.

Pulmonary cystic disease in HIV positive individuals in the Democratic Republic of Congo: three case reports.

Pulmonary emphysema and bronchiectasis in HIV seropositive patients has been described in the presence of injection drug use, malnutrition, repeated opportunistic infections, such as Pneumocytis jirovici pneumonia and Mycobacterium tuberculosis infection, and has been linked to the presence of HIV virus in lung tissue. Given the high burden of pulmonary infections and malnutrition among people living with HIV in resource poor settings, these individuals may be at increased risk of developing pulmonary emphysema, potentially reducing the long term benefit of antiretroviral therapy (ART) if initiated late in the course of HIV infection.In this report, we describe three HIV-infected individuals (one woman and two children) presenting with extensive pulmonary cystic disease.