RESUMO
BACKGROUND: Complete recovery of the CD4 T cell count is uncommon among chronically HIV-infected individuals with very low pre-treatment CD4 count. We studied the prevalence of chronically immune recovery and its associated factors including immune characteristics chronic HIV-infected Thais. METHODS: Treatment-naïve participants (n â= â375) from the HIV-NAT 006 cohort with a pre-treatment CD4 T cell count after initiating antiretroviral therapy (ART) and having achieved a suppressed viremia (HIV-RNA level â< â400 copies/mL) were retrospectively followed at the Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Suboptimal immune recovery (SIR) was defined as having a CD4+ T cell count <200 âcells/mm3 for 3 years after ART initiation. A case-control sub-study matched for age, sex and pre-ART CD4 T cell count was conducted to compare immunological characteristics between SIR (n â= â17) and non-SIR (n â= â24) participants. Immunological biomarkers such as interleukin-7 (IL-7) and soluble CD14 (sCD14) and other covariates including cytomegalovirus (CMV) DNA level, baseline hemoglobin level, hepatitis B and C co-infections, and T cell subsets associated with immune activation and exhaustion were evaluated. RESULTS: Among 375 participants with pre-ART CD4 T cell counts < 200 âcells/mm3, the prevalence of SIR was 39.7%, 19.7% and 7.7% at years 1, 2 and 3 after starting ART, respectively. In a multivariate analysis, a pre-ART CD4 T cell count ≤100 âcells/mm3 (adjusted odds ratio [aOR] 9.45, 95% CI 2.92-30.61, p â< â0.001), older age (aOR 1.07, 95% CI 1.01-1.13, p â= â0.029) and baseline HIV-RNA level (aOR 0.36, 95% CI 0.21-0.59, p â< â0.001) were independently associated with SIR at year 3 after ART initiation. In the matched case-control sub-study (cases â= â17, controls â= â24), there was a higher prevalence of hepatitis C co-infection (18.8% vs. 0%, p â= â0.05), lower sCD14 levels (mean, 6.23 vs. 6.27 log10 âpg/mL, p â= â0.04), lower CD8 T cell counts (mean, 514 vs. 876, p â= â0.0003), lower CD4/CD8 T cell ratio (mean, 0.27 vs. 0.41, p â= â0.01) and higher expression of PD1 on CD8+ T cells (74.2% vs. 65.1%, p â= â0.02) observed in SIR participants compared to their non-SIR counterparts at year 3 after ART initiation. CONCLUSIONS: Nearly 10% of the study participants who had achieved virological suppression failed to recover a CD4 T cell count > 200 cells/mm3 after 3 years of ART which was with a very low pre-ART CD4 T cell count and older age. The long-term clinical outcomes of SIR participants need to be further explored.
RESUMO
BACKGROUND: A prime-boost vaccination regimen with ALVAC-HIV (vCP1521) administered intramuscularly at 0, 4, 12, and 24 weeks and gp120 AIDSVAX B/E at 12 and 24 weeks demonstrated modest efficacy of 31.2% for prevention of HIV acquisition in HIV-uninfected adults participating in a community-based efficacy trial in Thailand. METHODOLOGY/PRINCIPAL FINDINGS: Reactogenicity was recorded for 3 days following vaccination. Adverse events were monitored every 6 months for 3.5 years, during which pregnancy outcomes were recorded. Of the 16,402 volunteers, 69% of the participants reported an adverse event any time after the first dose. Only 32.9% experienced an AE within 30 days following any vaccination. Overall adverse event rates and attribution of relatedness did not differ between groups. The frequency of serious adverse events was similar in vaccine (14.3%) and placebo (14.9%) recipients (pâ=â0.33). None of the 160 deaths (85 in vaccine and 75 in placebo recipients, pâ=â0.43) was assessed as related to vaccine. The most common cause of death was trauma or traffic accident. Approximately 30% of female participants reported a pregnancy during the study. Abnormal pregnancy outcomes were experienced in 17.1% of vaccine and 14.6% (pâ=â0.13) of placebo recipients. When the conception occurred within 3 months (estimated) of a vaccination, the majority of these abnormal outcomes were spontaneous or elective abortions among 22.2% and 15.3% of vaccine and placebo pregnant recipients, respectively (pâ=â0.08). Local reactions occurred in 88.0% of vaccine and 61.0% of placebo recipients (p<0.001) and were more frequent after ALVAC-HIV than AIDSVAX B/E vaccination. Systemic reactions were more frequent in vaccine than placebo recipients (77.2% vs. 59.8%, p<0.001). Local and systemic reactions were mostly mild to moderate, resolving within 3 days. CONCLUSIONS/SIGNIFICANCE: The ALVAC-HIV and AIDSVAX B/E vaccine regimen was found to be safe, well tolerated and suitable for potential large-scale use in Thailand. TRIAL REGISTRATION: ClinicalTrials.govNCT00223080.
