A little boy having a bit of trouble reaching the window sill of the pharmacy at the Pediatric Infectious Diseases Clinic at the Mulago Hospital , Kampala , Uganda .

Bristol-Myers Squibb Foundation

Mortality and ART efficacy outcomes in children < 12 years on ART in Lesotho , Swaziland and Malawi

Currently over 68,000 patients are receiving care and treatment within the BIPAI network in Africa and Romania .

Hypothesis

HAART as administered to children with HIV / AIDS at the BIPAI COE ’ s in Africa will result in comparable rates of true mortality to those observed in the United States .

Primary objective

The primary objective is to determine the rate of mortality on HAART over a twelve month period in children , aged 0 to 12 years , enrolled onto therapy at the COE ’ s .

Secondary objectives a ) to determine clinical outcomes of children enrolled at the three COEs , in terms of efficacy of HAART , adherence to ARV medication , level of appropriate prescription of cotrimoxazole and correction or improvement of malnutrition .

b ) to determine the possible relationships between a range of baseline factors and mortality .

Methods

This retrospective study utilized existing programmatic data from the Lesotho , Malawi , and Swaziland COEs .

ART-naïve HIV-infected children < 12 years of age initiating ART and being followed for 12 months were included . Annualized mortality was calculated at three month intervals between February 2008 and September 2009 . In addition , mortality rates were estimated overall and for each demographic and clinical subgroup per 100 person-years under a Poisson distribution . Efficacy of ART was defined as improvement in CD4 count of > 5 % from baseline for children < 5 years or increase of > 50 CD4 + cells / ml for children > 5-12 years during the first year on ART , with all deaths , discontinuations and lost to follow ups being counted failures .

Hazard ratios ( HRs ) and 95 % confidence intervals were estimated for the univariate associations between overall mortality and each demographic and clinical subgroup . The univariate and multivariate analyses were repeated to determine the demographic and clinical factors associated with outcomes with 12 months of HAART .

Results

Annualized mortality ( Sep . 2009 ) 4.4 % ( 102 / 2306 ) Overall mortality

1.98 deaths / 100 person years

Adherence to HAART ( Malawi and Swaziland )

77.0 % had ≥ 95 % adherence

( 962 / 1250 ) % appropriate cotrimoxazole coverage 88.6 % ( 1159 / 1308 ) % improvement in malnutrition since

enrollment

Table 1 : Top-line results

87.4 % ( 553 / 633 )

Figure 1 . Kaplan-Meier curve for age at study entry

The overall mortality rate was 1.98 deaths / 100 person-years ( 95 % CI 1.62-2.39 ). This is comparable to overall mortality rates for HIV infected children reported for the United States . 3

The US Pediatric AIDS Clinical Trials Group 219 / 291C reported an overall mortality rate of 1.47 deaths / 100 person-years ( 95 % CI 1.31-1.65 ) for children enrolled and followed up between April 1993 and December 2006 3 . However , they reported a declining mortality rate over the study years with mortality rates between 0.5-0.8 deaths / 100 person-years between 2000 and 2006 in the post-HAART era . In addition , comparisons between the mortality rates between the PACTG and BIPAI cohorts should be made with caution because of the different age distributions between the cohorts .

Mortality was highest in the first year of HAART treatment , 78 % of all deaths occurring within that period . With regard to baseline factors , age less than one year , WHO stage IV and evidence of malnutrition at enrolment were associated with higher mortality , while primary caregiver other than the mother or father was associated with lower mortality ( figure 1 and table 2 ). Country and gender were unrelated to mortality .

Table 2 : Baseline factors affecting mortality

Conclusions

Despite the challenges associated with the public health approach to implementing pediatric-focused ART programs in developing countries , low mortality and good treatment efficacy outcomes in children can be achieved . At BIPAI COEs in southern Africa mortality rates have fallen progressively over time and now

Authors :

R . S . Wanless 1 , M . Kabue 2 , P . Kazembe 2 , E . Mohapi 3 , L . Thahane 3 , A . Devlin 3 , N . S . Hailu 4 , D . McCollum 4 , N . Calles 5 , G . Schutze 5 , M . Kline 5 , M . Mizwa 5 , Chantal Caviness 5 , Shaun Krog 6 approach those observed in developed countries in similar HIV-infected populations .

References

Baylor College of Medicine International Pediatric AIDS Initiative at Texas Children ’ s Hospital , Fundatia Baylor Marea Neagra , Constanta , Romania ,

Baylor College of Medicine – Abbott Fund Children ’ s Centre of Excellence , Lilongwe , Malawi ,

Baylor College of Medicine – Bristol Myers Squibb Children ’ s Clinical Centre of Excellence , Maseru , Lesotho ,

Baylor College of Medicine – Bristol Myers Squibb Children ’ s Clinical Centre of Excellence , Mbabane , Swaziland ,

Baylor College of Medicine International Pediatric AIDS Initiative at Texas Children ’ s Hospital , Houston , United States ,

VirtualPurple Professional Services , Durban , KwaZulu-Natal , South Africa

1 . UNAIDS / WHO AIDS Epidemic Update : December 2006 , accessed online at http :// data . unaids . org / pub / EpiReport / 2006 / 2006 _ EpiUpdate _ en . pdf 2 . Children and AIDS : Second Stocktaking Report , April 2008 . Accessed online at www . unicef . org / publications / index _ 43451 . html 3 . Declines in mortality rates and changes in causes of death in HIV-1- infected children during the HAART era . Michael T . Brady , James M . Oleske , Paige L . Williams et al . for the Pediatric AIDS Clinical Trials Group219 / 219C Team . J Acquir Immune Defic Syndr 2010 ; 53:86 – 94 .

A little boy having a bit of trouble reaching the window sill of the pharmacy at the Pediatric Infectious Diseases Clinic at the Mulago Hospital , Kampala , Uganda .