Study Population
Among the 210 HIV-infected children included in phase 2 of the Pediacam study, 149 who initiated ART no later than the age of one year were alive at two years and considered for this analysis (Figure 1). Of the 61 HIV-infected children who were not included in this study, 12 where deceased before ART, 5 were lost to follow-up or relocated before ART, 3 were placed on ART after age 12 months, 38 deceased within the first two years of ART and 3 were lost to follow-up before 2 years of ART initiation. Among the 149 children (82 boys) followed-up and still alive at two years after ART initiation, with ART started during the first year of life, three quarters (73.9%) were enrolled in the two Yaounde sites (Table 1). The median age of the children at two years after ART initiation (origin of time for this analysis) was 28.5 months (IQR: 27.1 – 30.0). Most (75.6%) were living with their mothers (with or without their fathers) in households of which 39.4% had running water, 93.6% electricity, and 51.1% a functional refrigerator. The ART regimen two years after treatment initiation was comprised of lopinavir boosted with ritonavir (74.5%) or nevirapine (25.5%), with a median percentage of CD4 lymphocytes of 33.6% (24.1 - 40.4).
At two years after ART initiation, most of the children (77.2%) had achieved a confirmed VS at least once (43) and a viral load measurement was available for 134, of whom 67.2% were < 400 copies/mL («controlled viral load»). Among the 15 other children, the last available viral load was ≥ 400 copies/mL for 12.
We compared the characteristics at two years of treatment according to a viral load below or above 400 copies/mL by grouping together the children whose viral load was ≥ 400 copies/mL or not measured. The children with VS at two years of treatment were more often girls than boys (62.2% versus 37.8%, p = 0.017) and almost all (96.7%) had achieved confirmed virological success (CVS) at least once before two years of treatment, whereas this was true for only 45.5% of the other children (p < 0.001).
Mortality and retention in care between two and five years after ART initiation
Among the 149 children, alive at two years of treatment, included in this study, a viral load measurement was available at M60 for 121 (84.0%) and 23 (15.4%) did not have viral load measurements at five years of ART with no information concerning death (Table2). Of these, 12 (8.1%) were lost to follow-up before M24. Five (3.4%) deaths were recorded M24 and M60, corresponding to a death rate of 3.0% (95%CI: 0.2% – 5.8%) estimated using the Kaplan Meier method. Among them, two occurred in children with a viral load ≥ 400 copies/mL and three in children whose viral load was unavailable at two years of treatment, whereas there were no deaths among children with VS at two years of treatment.
Immunological status at five years of antiretroviral treatment
Among the children included in this study, almost three quarters had a high CD4 percentage level (≥25%) at 5 years of ART (Table 2).
Virologic control at five years of antiretroviral treatment
Virologic control at five years of ART was estimated at 66.8% (60.1 - 73.5) among the 144 children still alive after five years of treatment but 23 (16.0%) did not have an available viral load measurement at that deadline (Table 2). Among the children who were virologically controlled (viral load < 400 copies/mL) at two years of treatment, the probability of maintaining virologic control at five years, estimated using the Kaplan-Meier method, was 64.0% (54.0 - 74.0), (Table 2 and figure 2). Of those whose viral load was uncontrolled or unknown at two years of ART, the probability of achieving a viral load < 400 copies/mL between two and five years was 76.0% (63.0 - 89.0).
Genotypic resistance test of HIV to antiretroviral drugs was performed for a sample of 25 children whose viral load remained high (≥1000 copies/mL) for at least three consecutive medical visits during the study. Of these, 15 (60.0%) were boys and 18 (72.0%) have initiated lopinavir-based ART. The distribution of sex and type of ART in this sample was comparable to the study population. Among these children, 5 (20.0%) rebounded to viral load ≥1,000 copies/mL during the study period for at least 3 consecutive visits before suppressing to viral load <400 copies/mL no later than five years of ART. Overall, respectively 14 (56.0%), 9 (36.0%) and 2 (8.0%) of these children had no resistance, only lamivudine (3TC) resistance (not altering the effectiveness of current ART regimen) and resistance to non-3TC drugs (altering the effectiveness of current ART regimen). The resistance pattern did not differ by whether the child was suppressed or not at 5 years of ART, according to the Fisher exact test (p=0.440).
Factors associated with virological success at five years of antiretroviral treatment
In univariate analysis (Table 3), VS at five years of treatment (viral load < 400 copies/mL versus viral load ≥ 400 copies/mL or not measured) was associated with female gender (OR = 2.1 (1.0-4.4), p = 0.041) and achievement of confirmed virological success (at least two consecutive viral loads < 400 copies/mL during the first two years of treatment) at least once within the first two years of ART (OR = 3.0 (1.3-6.9), p = 0.010). There was a non-significant association between VS at M60 and controlled viral load (VL< 400 copies/mL) at two years of ART initiation (OR= 2.2 (0.9-4.8), p = 0.061), being followed at “Centre Hospitalier d’Essos” versus “Centre Mère et Enfant de Yaoundé” and “Hôpital Laquintinie de Douala” (OR=2.8 (1.0-7.6), p=0.056) and absence of missed doses during the last three days before the M60 visit (OR = 2.8 (0.9-8.7), p = 0.076). In multivariate analysis (Table 3), the only factors associated with VS at five years of treatment was achievement of confirmed virological success at least once within the first two years of ART (adjusted OR = 2.7 (1.1-6.8); p = 0.033) and the trend between VS and absence of missed doses during the last three days before the M60 visit remained (adjusted OR = 2.7 (0.9-10.4), p = 0.075).