Paediatric HIV infection in Maputo, Mozambique : Horizontal transmission, treatment outcomes and drug resistance

Abstract: This thesis describes observational studies performed at the main reference centre for paediatric HIV care and management in Mozambique, which is one of the countries most strongly affected by the AIDS pandemic. These studies focused on horizontal transmission, treatment outcomes and paediatric antiretroviral drug resistance in a cohort of HIV-1-infected children. The majority of children infected by HIV get the infection from their mothers during pregnancy, delivery or through breastfeeding, in what is known as mother-to-child transmission of HIV-1. However, some of them, in a percentage that is not well ascertained in resource-constrained settings, can be infected through other modes. In the first paper, we explored different risk factors that might have contributed to HIV infection in a small cohort of HIV-infected children born to HIV non-infected mothers. A case control study strongly suggested health care as the possible source of infection for many of these children, with blood transfusion being significantly associated with HIV infection. Paediatric antiretroviral treatment (ART) has been available for children in Mozambique since December 2003. During the period between December 2003 and December 2008, more than 4700 children aged 0-18 years were recruited, and 1125 received ART in our centre. Survival frequency was 87% after 60 months of antiretroviral treatment. The median follow-up time after ART initiation in the cohort was 24.4 months (IQR 13.5-35.7). After 5 years of ART, 710 children (98.1%) were on first-line treatment, and 21 children (1.9%) were on second-line treatment. After 12 months on ART, there was an improvement in mean (SD) CD4% from 12.3 (6.3) to 27.7 (8.8) (p<0.001). A viral load (VL) cross-sectional evaluation was made in 2006 in 495 children on ART; 72.7% had a VL of < 50 copies/mL. These clinical outcomes are encouraging and provide stronger evidence in support of wider scale-up of long-term treatment of HIV-infected children with NNRTI-based first-line antiretroviral drugs in sub- Saharan Africa. Resistance to paediatric antiretroviral drugs in children in sub-Saharan Africa has not been documented. We performed genotypic resistance tests in 84 available samples from 135 treated children with VL ?50 copies/mL among children in whom cross-sectional viral load assessment was carried out in 2006. Approximately 92% of the viruses found in this cohort were resistant to lamivudine and/or nevirapine, and 15% were resistant to stavudine. Twenty children (24%) harboured virus with an extended spectrum of cross-resistance. A multivariate analysis revealed that the only factor associated with this extended resistance profile was treatment duration (OR: 6.67 [95% CI 1.24; 35.93], p<0.05 for treatment >24 months), with a per month increase of 1.09 [1.02-1.16] (p=0.0065). Opportunistic infections are frequent in HIV-1-infected children, as are oncology-related infections. To date, there are no published reports investigating clinical outcomes of HIV-1-infected children with Kaposi s sarcoma. We described chemotherapy and ART outcomes in a cohort of 28 children with histological confirmed AIDS-associated Kaposi s sarcoma (AKS). The cohort included twenty (71%) males and 8 females who were moderately ill, severely immunosuppressed children. The mean patient age was 8.3 (range 2-16) years, and the mean (SD) follow-up time was 27.3 (14.9) months. All patients were ART naive. Twenty-four children on ART were alive at 6 months after completing chemotherapy, corresponding to a survival rate of 85.7%. The CD4 % increased from a mean (SD) of 16% (9.2) to 29.2% (27.1) before initiation and after cessation of chemotherapy (p=0.02). Our findings in children confirmed what has been observed in adults: a good clinical outcome with an acceptable toxicity of combined highly active antiretroviral therapy (HAART) and chemotherapy in ARTnaïve, HIV-1-infected children with associated Kaposi s sarcoma.