Growth, immune and viral responses in HIV infected African children receiving highly active antiretroviral therapy: a prospective cohort study.

BACKGROUND: Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes. METHODS: A prospective cohort of HIV infected children were initiated on HAART and followed for 48 weeks. Body mass index for age z scores(BAZ), weight and height-for-age z scores (WAZ & HAZ) were calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12 weeks. Treatment outcomes were classified according to; both virological and immunological success (VS/IS), virological failure and immunological success (VF/IS). virological success and immunological failure (VS/IF) and both virological and immunological failure (VF/IF). RESULTS: From March 2004 until May 2006, 124 HIV infected children were initiated on HAART. The median age (IQR) was 5.0 years (2.1 - 7.0) and 49% (61/124) were female. The median [95% confidence interval (CI)] BAZ, WAZ and HAZ at baseline were 0.29 (-2.9, -1.2), -1.2 (-2.1, -0.5) and -2.06 (-2.9, -1.2) respectively. Baseline median CD4 cell % and log10 HIV-1 RNA were; 11.8% (7.5-18.0) and 5.6 (5.2-5.8) copies/ml. By 48 weeks, mean WAZ and HAZ in the VF/IS group, which was younger, increased from - 0.98 (SD 1.7) to + 1.22 (SD 1.2) and from -1.99 (1.7) to + 0.76 (2.4) respectively. Mean increase in WAZ and HAZ in the VS/IF group, an older group was modest, from -1.84 (1.3) to - 0.41 (1.2) and -2.25 (1.2) to -1.16 (1.3) respectively. Baseline CD4 cell % [OR 6.97 95% CI (2.6 -18.6)], age [OR 4.6 95% CI (1.14 -19.1)] and WHO clinical stage [OR 3.5 95%CI (1.05 -12.7)] were associated with successful treatment outcome. CONCLUSIONS: HIV infected Ugandan children demonstrated a robust increase in height and weight z scores during the first 48 weeks of HAART, including those who failed to completely suppress virus. Older children initiating HAART with severe immune suppression were less likely to achieve a successful treatment outcome. These data emphasize the importance of initiating HAART early to ensure adequate immune and growth responses.

Analysis of drug resistance in children receiving antiretroviral therapy for treatment of HIV-1 infection in Uganda.

We analyzed drug resistance in HIV-infected Ugandan children who received antiretroviral therapy in a prospective, observational study (2004-2006); some children had prior single-dose nevirapine (sdNVP) exposure. Children received stavudine (d4T), lamivudine (3TC), and nevirapine (NVP); treatment was continued if they were clinically and immunologically stable. Samples with >1,000 copies/ml HIV RNA were analyzed by using the ViroSeq HIV Genotyping System (ViroSeq). Subtype A and D pretreatment samples also were analyzed with the LigAmp assay (for K103N, Y181C, and G190A). ViroSeq results were obtained for 74 pretreatment samples (35 from sdNVP-exposed children (median age, 19 months) and 39 from sdNVP-unexposed children (median age, 84 months). This included 39 subtype A, 22 subtype D, 1 subtype C, and 12 inter-subtype recombinant samples. One sample had nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance, one had nucleoside reverse transcriptase inhibitor (NRTI) resistance, and three had protease inhibitor (PI) resistance. Y181C was detected by using LigAmp in five pretreatment samples [four (14.8%) of 37 samples from sdNVP-exposed children, one (4.2%) of 24 samples from children without prior sdNVP exposure; p = 0.35]. Among children who were not virally suppressed at 48 weeks of treatment, all 12 tested had NNRTI resistance, as well as resistance to 3TC and emtricitibine (FTC); three had resistance to other NRTIs. Seven of those children had a ViroSeq result at 96 weeks of treatment; four of the seven acquired resistance to additional NRTIs by 96 weeks. In Uganda, clinically and immunologically stable children receiving nonsuppressive antiretroviral treatment regimens are at risk for development of drug resistance.

Response to antiretroviral therapy in HIV-infected Ugandan children exposed and not exposed to single-dose nevirapine at birth.

OBJECTIVE: To compare the response to a nevirapine (NVP)-based highly active antiretroviral therapy (HAART) in HIV-infected Ugandan children, exposed and nonexposed to single-dose NVP (sd NVP) at birth. METHODS: HIV-infected study children were initiated on stavudine/lamivudine/NVP as a fixed dose combination. CD4 cell percent and HIV-1 RNA were documented at baseline, 12, 24, 36, and 48 weeks post-initiation of HAART. RESULTS: Ninety-two children were enrolled in the study, 44 in the sd NVP-exposed and 48 in the nonexposed cohort. The median age at enrollment was 1.7 years [interquartile range (IQR) 1.2-2.4] and 7.8 years (IQR 5.9-9.2) in the sd NVP-exposed and nonexposed cohorts,respectively (P < 0.001). At baseline and week 48 post-HAART, the median CD4 cell percentages were 14% and 33% for the NVP-exposed group and 8% and 22.5% in the nonexposed group (P < 0.0001). The median (IQR) viral load at baseline was 650,568 (359,979-2,086,613) RNA copies/mL and 239,027 (105,904-494,813) RNA copies/mL in the NVP-exposed and nonexposed cohorts, respectively. After 48 weeks of HAART, 76% of the NVP-exposed and 80% of the nonexposed children had a median viral load of < 400 copies/mL (P = 0.74). CONCLUSIONS: Both HIV-infected Ugandan older infants and children that were exposed and not exposed to sd NVP at birth had favorable treatment outcomes on NVP-containing HAART.