Publications

Trends in the clinical characteristics of HIV-infected patients initiating antiretroviral therapy in Kenya, Uganda and Tanzania between 2002 and 2009.

  BACKGROUND: East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIV-infected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described. METHODS: We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of ART initiation and use of stavudine (D4T) or nevirapine (NVP) were identified using a log-link Poisson model with robust standard errors. RESULTS: Among 48,658 patients (69% from Kenya, 22% from Uganda and 9% from Tanzania) accessing ART at 30 clinic sites, the median age at the time of ART initiation was 37 years (IQR: 31-43) and 65% were women. Pre-therapy CD4 counts rose from 87 cells/mm3 (IQR: 26-161) in 2002-03 to 154 cells/mm3 (IQR: 71-233) in 2008-09 (p<0.001). Accessing ART at advanced disease peaked at 35% in 2005-06 and fell to 27% in 2008-09. D4T use in the initial regimen fell from a peak of 88% in 2004-05 to 59% in 2008-09, and a greater extent of decline was observed in Uganda than in Kenya and Tanzania. Self-pay for ART peaked at 18% in 2003, but fell to less than 1% by 2005. In multivariable analyses, accessing ART at advanced immunosuppression was associated with male sex, women without a history of treatment for prevention of mother to child transmission (both as compared with women with such a history) and younger age after adjusting for year of ART initiation and country of residence. Receipt of D4T in the initial regimen was associated with female sex, earlier year of ART initiation, higher WHO stage, and lower CD4 levels at ART initiation and the absence of co-prevalent tuberculosis. CONCLUSIONS: Public health ART services in east Africa have improved over time, but the fraction of patients accessing ART with advanced immunosuppression is still high, men consistently access ART with more advanced disease, and D4T continues to be common in most settings. Strategies to facilitate access to ART, overcome barriers among men and reduce D4T use are needed. AbstractBACKGROUND:East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIV-infected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described.METHODS:We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of ART initiation and use of stavudine (D4T) or nevirapine (NVP) were identified using a log-link Poisson model with robust standard errors.RESULTS:Among 48,658 patients (69% from Kenya, 22% from Uganda and 9% from Tanzania) accessing ART at 30 clinic sites, the median age at the time of ART initiation was 37 years (IQR: 31-43) and 65% were women. Pre-therapy CD4 counts rose from 87 cells/mm3 (IQR: 26-161) in 2002-03 to 154 cells/mm3 (IQR: 71-233) in 2008-09 (p<0.001). Accessing ART at advanced disease peaked at 35% in 2005-06 and fell to 27% in 2008-09. D4T use in the initial regimen fell from a peak of 88% in 2004-05 to 59% in 2008-09, and a greater extent of decline was observed in Uganda than in Kenya and Tanzania. Self-pay for ART peaked at 18% in 2003, but fell to less than 1% by 2005. In multivariable analyses, accessing ART at advanced immunosuppression was associated with male sex, women without a history of treatment for prevention of mother to child transmission (both as compared with women with such a history) and younger age after adjusting for year of ART initiation and country of residence. Receipt of D4T in the initial regimen was associated with female sex, earlier year of ART initiation, higher WHO stage, and lower CD4 levels at ART initiation and the absence of co-prevalent tuberculosis.CONCLUSIONS:Public health ART services in east Africa have improved over time, but the fraction of patients accessing ART with advanced immunosuppression is still high, men consistently access ART with more advanced disease, and D4T continues to be common in most settings. Strategies to facilitate access to ART, overcome barriers among men and reduce D4T use are needed.

Outcomes of HIV-exposed children in western Kenya: efficacy of prevention of mother to child transmission in a resource-constrained setting

  OBJECTIVES: To compare rates of mother to child transmission of HIV and infant survival in women-infant dyads receiving different interventions in a prevention of Mother to Child Transmission (pMTCT) program in western Kenya. DESIGN: Retrospective cohort study using prospectively collected data stored in an electronic medical record system. SETTING: Eighteen HIV clinics in western Kenya. POPULATION: HIV-exposed infants enrolled between February 2002 and July 2007, at any of the United States Agency for International Development-Academic Model Providing Access To Healthcare partnership clinics. MAIN OUTCOME MEASURES: Combined endpoint (CE) of infant HIV status and mortality at 3 and 18 months. ANALYSIS: Descriptive statistics, chi Fisher exact test, and multivariable modeling. RESULTS: Between February 2002 and July 2007, 2477 HIV-exposed children were registered for care by the United States Agency for International Development-Academic Model Providing Access To Healthcare partnership pMTCT program before 3 months of age. Median age at enrollment was 6.1 weeks; 50.4% infants were male. By 3 months, 31 of 2477 infants (1.3%) were dead and 183 (7.4%) were lost to follow-up. One thousand (40%) underwent HIV DNA Polymerase Chain Reaction virologic test at a median age of 8.3 weeks: 5% were HIV infected, 89% uninfected, and 6% were indeterminate. Of the 968 infants with specific test results or mortality data at 3 months, the CE of HIV infection or death was reached in 84 of 968 (8.7%) infants. The 3-month CE was significantly impacted (A) by maternal prophylaxis [51 of 752 (6.8%) combination antiretroviral therapy (cART); 8 of 69 (11.6%) single-dose nevirapine (sdNVP); and 25 of 147 (17%) no prophylaxis (P < 0.001)] and (B) by feeding method for the 889 of 968 (91.8%) mother-infant pairs for which feeding choice was documented [5 of 29 (17.2%) exclusive breastfeeding; 13 of 110 (11.8%) mixed feeding; and 54 of 750 (7.2%) formula feeding (P = 0.041)]. Of the 1201 infants > or = 18 months of age: 41 (3.4%) were deceased and 329 (27.4%) were lost to follow-up. Of 621 of 831 (74.7%) infants tested, 65 (10.5%) were infected resulting in a CE of 103 of 659 (15.6%). CE differed significantly by maternal prophylaxis [52 of 441 (11.8%) for cART; 13 of 96 (13.5%) for sdNVP; and 38 of 122 (31.2%) no therapy group (P < 0.001)] but not by feeding method for the 638 of 659 (96.8%) children with documented feeding choice [7 of 35 (20%) exclusive breastfeeding, 14 of 63 (22.2%) mixed, and 74 of 540 (13.7%) formula (P = 0.131)]. On multivariate analysis, sdNVP (odds ratio: 0.4; 95% confidence interval: 0.2 to 0.8) and cART (odds ratio: 0.3; 95% confidence interval: 0.2 to 0.6) were associated with fewer CE. At 18 months, feeding method was not significantly associated with the CE. CONCLUSIONS: Though ascertainment bias is likely, results strongly suggest a benefit of antiretroviral prophylaxis in reducing infant death and HIV infection, but do not show a benefit at 18-months from the use of formula. There was a high rate of loss to follow up, and adherence to the HIV infant testing protocol was less than 50% indicating the need to address barriers related to infant HIV testing, and to improve outreach and follow-up services. AbstractOBJECTIVES:To compare rates of mother to child transmission of HIV and infant survival in women-infant dyads receiving different interventions in a prevention of Mother to Child Transmission (pMTCT) program in western Kenya.DESIGN:Retrospective cohort study using prospectively collected data stored in an electronic medical record system.SETTING:Eighteen HIV clinics in western Kenya.POPULATION:HIV-exposed infants enrolled between February 2002 and July 2007, at any of the United States Agency for International Development-Academic Model Providing Access To Healthcare partnership clinics.MAIN OUTCOME MEASURES:Combined endpoint (CE) of infant HIV status and mortality at 3 and 18 months.ANALYSIS:Descriptive statistics, chi Fisher exact test, and multivariable modeling.RESULTS:Between February 2002 and July 2007, 2477 HIV-exposed children were registered for care by the United States Agency for International Development-Academic Model Providing Access To Healthcare partnership pMTCT program before 3 months of age. Median age at enrollment was 6.1 weeks; 50.4% infants were male. By 3 months, 31 of 2477 infants (1.3%) were dead and 183 (7.4%) were lost to follow-up. One thousand (40%) underwent HIV DNA Polymerase Chain Reaction virologic test at a median age of 8.3 weeks: 5% were HIV infected, 89% uninfected, and 6% were indeterminate. Of the 968 infants with specific test results or mortality data at 3 months, the CE of HIV infection or death was reached in 84 of 968 (8.7%) infants. The 3-month CE was significantly impacted (A) by maternal prophylaxis [51 of 752 (6.8%) combination antiretroviral therapy (cART); 8 of 69 (11.6%) single-dose nevirapine (sdNVP); and 25 of 147 (17%) no prophylaxis (P < 0.001)] and (B) by feeding method for the 889 of 968 (91.8%) mother-infant pairs for which feeding choice was documented [5 of 29 (17.2%) exclusive breastfeeding; 13 of 110 (11.8%) mixed feeding; and 54 of 750 (7.2%) formula feeding (P = 0.041)]. Of the 1201 infants > or = 18 months of age: 41 (3.4%) were deceased and 329 (27.4%) were lost to follow-up. Of 621 of 831 (74.7%) infants tested, 65 (10.5%) were infected resulting in a CE of 103 of 659 (15.6%). CE differed significantly by maternal prophylaxis [52 of 441 (11.8%) for cART; 13 of 96 (13.5%) for sdNVP; and 38 of 122 (31.2%) no therapy group (P < 0.001)] but not by feeding method for the 638 of 659 (96.8%) children with documented feeding choice [7 of 35 (20%) exclusive breastfeeding, 14 of 63 (22.2%) mixed, and 74 of 540 (13.7%) formula (P = 0.131)]. On multivariate analysis, sdNVP (odds ratio: 0.4; 95% confidence interval: 0.2 to 0.8) and cART (odds ratio: 0.3; 95% confidence interval: 0.2 to 0.6) were associated with fewer CE. At 18 months, feeding method was not significantly associated with the CE.CONCLUSIONS:Though ascertainment bias is likely, results strongly suggest a benefit of antiretroviral prophylaxis in reducing infant death and HIV infection, but do not show a benefit at 18-months from the use of formula. There was a high rate of loss to follow up, and adherence to the HIV infant testing protocol was less than 50% indicating the need to address barriers related to infant HIV testing, and to improve outreach and follow-up services.