CHAPTER THREE
3.1 RESULTS
3.1.2 CD4 + T-cell percentage and viral load estimation
3.1.2.2 CD4 + T-cell percentage and viral load estimation in the continuous treatment group
Figures 14a and 14b demonstrate the effect of continuous ARV therapy on %CD4+ T- cells and viral load over a two-year period in HIV-1 chronically infected children (n=21).
(14a)
0 weeks
12 weeks
24 weeks
48 weeks
72 weeks
96 weeks 0
10 20 30 40 50 60
n=21 n=21 n=21 n=20 n=16 n=15
% CD4 T-cell
Figure 14(a). Demonstrates the pretreatment %CD4+ T-cell in relation to the
%CD4+ T-cell over the two-year study period for the twenty-one children who received continuous ARV therapy (this includes the six children who did not have treatment interruptions but were randomized to the treatment interruption arm).
The yellow background indicates the treatment phase. The change in the n values at 48, 72 and 96 weeks, indicates the children who were disenrolled due to treatment non-adherence and development of drug resistance.
(14b)
0
weeks
12 weeks
24 weeks
48 weeks
72 weeks
96 weeks 0
1 2 3 4 5 6 7
n=21 n=21 n=21 n=16 n=15 n=21
Log viral load
Figure 14(b). The pre-treatment log viral load is shown in relation to the log viral loads over the two year study period for the twenty-one children who received continuous ARV therapy (this includes the six children who did not have treatment interruptions but were randomized to the treatment interruption arm). The yellow background indicates the treatment phase. The change in the n values at 48, 72 and 96 weeks, indicates the children who were disenrolled due to treatment non- adherence and development of drug resistance.
The median %CD4+ T-cell increased from 18% before antiretroviral treatment to 35% at 96 weeks (fig 14a). Six children (PARV 04, PARV 06, PARV 15, PARV 17, PARV 21 and PARV 30) although randomised to the treatment interruption group, did not have any treatment interruptions due to their viral loads being detectable at 24 weeks. They therefore received continuous treatment for the study period. Two of the six children were monitored until 96 weeks and together with the other four children they were referred and subsequently monitored on the National Roll-Out Program.
PARV 04, a five year old female child who had a 24% pre-HAART CD4% which increased to ≥30% up until 48 weeks on treatment. The pre-HAART viral load was log
4.76 which decreased to undetectable levels (log 2.09) at 12 weeks but was detectable (log 2.38) at 24 weeks therefore this child had to continue with the ARV treatment for another six months but the viral load was still detectable (log 2.97) at 48 weeks.
Resistance testing was performed at this timepoint. The M184V mutation to 3TC had developed. This child also had a pre-HAART drug mutation G190EG to NNRTI.
PARV 06, a four year old male child, had a low CD4 count (8%) and a high viral load (log 5.5) before starting antiretroviral treatment. Despite this severe deterioration of the immune system, with the antiretroviral therapy, a good increase of CD4 count (18%) was noted at 12 weeks after starting antiretroviral treatment. Although the CD4% maintained
~20%, the viral load decreased to undetectable levels (log 2.09) at 12 weeks but was detectable (log10 = 4.20) and (log10= 4.08) at 24 and 48 weeks respectively. It was discovered that this child had contracted another viral infection about the 18th week on ARV treatment, and with a detectable viral load, scheduled treatment interruptions were not implemented. Resistance testing was performed and five new mutations (T215Y, M184V, M41L, D67N and K70R) had developed, because PARV 06 had no drug mutations prior to starting HAART.
PARV 15, an eight year old female child, had a CD4 count of 16% prior to starting HAART which increased to ≥26% during the 96 weeks of follow-up. The pre-HAART viral load was log 4.92 but reached undetectable levels at 12 weeks (log 2.09). At 24 weeks the viral load increased to log 3.15 and continued to increase at 26 weeks (log 3.26), 48 weeks (log 3.53) until 50 weeks (log 4.59). Resistance testing was performed and M184V mutation had developed, since PARV 15 had no drug mutations before starting HAART. However, at 72 weeks, the viral load reached undetectable levels (log 2.09) but was detectable again (log 4.98) at 96 weeks.
PARV 17, a two year old male child, had a CD4 count of 17% and a viral load of log 4.85 before starting HAART. His CD4 count increased to 26% at 12 weeks on ARV treatment but his viral load did not reach undetectable levels (log 3.80). At 24 weeks his CD4 count was 24% and his viral load increased to log 5.65. A confirmation test was
performed at 28 weeks and his viral load was log 5.77. Resistance testing indicated that there were 4 mutations (M184V, K219N, D67N and K70R) that developed, as PARV 17 did not have any drug mutations before starting HAART.
PARV 21, a three year old female child, had a CD4 count of 12% and a viral load of log 5.17 before starting HAART. Although her CD4 counts increased significantly until the end of the study period 96 weeks (≥24%), her viral load was undetectable at 12 weeks on treatment but increased thereafter throughout the rest of the study period. There were no drug mutations before starting HAART but three mutations (M184V, D67N and K70R) had developed after initiation of HAART.
PARV 30 had a CD4 count of 18% before starting HAART. Although the CD4 count fluctuated a 10% increase was noted after treatment commenced. The pre-HAART viral load was log 5.04; however the viral load did not reach undetectable levels after treatment had commenced. Resistance testing indicated that M184V and Y181C drug mutations were present after the treatment had started as there were no drug mutations present before starting HAART.
For most children (in this cohort) receiving continuous ARV therapy, % CD4+ T-cells increased steadily over the study period from a median of 18% to 35% in 13/15 children (Figure 14a). Two subjects had < 25% CD4+ T-cells even at 96 weeks of ARV therapy.
One of the children had a very low CD4% before starting HAART and the other was treatment non-adherent. ARV therapy suppressed viraemia to undetectable levels as early as 12 weeks post therapy and remained for the duration of the two-year study period in some children, whilst in some children undetectable levels were never obtained even after two years, due to drug resistant mutations arising. In other cases, children had suppressed viraemia, but there was a viral load rebound detected as a result of non- adherence resulting in drug resistant mutations