Rapid Suppression of HIV-RNA Is Associated with Improved Control of Immune Activation in Mozambican Adults Initiating Antiretroviral Therapy with Low CD4 Counts

Abstract

The rapidity of HIV-RNA suppression after initiation of combined antiretroviral therapy (cART) may impact immune reconstitution in developing countries, where patients initiate cART at low CD4 T cell counts. One hundred and thirty-five HIV-1 Mozambican adults initiating cART were prospectively followed over 16 months within a larger observational study. Plasma HIV-RNA, CD4 counts, and CD8 T cell activation were monitored at the pre-cART visit and at 4, 10, and 16 months during cART. Of the 89 patients with available HIV-RNA data at pre-cART and 4 and 10 months post-cART, 68% (60/89) suppressed HIV-RNA at 4 months and were defined as "early virological controllers"(EC). Twenty of the 29 remaining patients who did not control HIV-RNA at 4 months did so at 10 months and were classified as "late virological controllers"(LC). Nine (10%) patients did not control HIV-RNA at either time point. Both initiating an EFV-containing cART regimen and having pre-cART tuberculosis were significantly associated with early HIV-RNA suppression if locked into a multivariate model [EFV OR: 13.6 (95% CI 1.7; 108.1) p = 0.014) tuberculosis OR: 11.0 (95% CI 1.4; 87.9) p = 0.024]. EC demonstrated significantly lower median activated CD8 T cells at 4, 10, and 16 months post-cART than did LC. Approximately 63% (12/19) of LC experienced reappearance of detectable HIV-RNA at 6 months postcontrol as compared to 15% (2/60) of EC (p = 0.001). This study suggests that rapid suppression of HIV-RNA may lead to a lower rate of reappearance of HIV-RNA, which could impact CD8 T cell activation levels in patients initiating cART at low CD4 counts.

The effect of tuberculosis treatment on virologic and CD4+ cell count response to combination antiretroviral therapy

“…Of these, 120 full-text articles were selected for review. In total, 18 articles [16-33] and five conference abstracts [34-38] were eligible. Five additional articles met our inclusion criteria: two from reference lists [39, 40] and three from Web of Science citation searches [41-43].…”

“…The other eight studies examined TB treatment as a secondary exposure; five aimed to describe general cART outcomes [16, 24, 28, 40, 41], and one each examined the primary exposures of timeliness of clinic attendance [17], β-defensin genomic copy number [22], and liver enzyme abnormalities [42]. The type of TB being treated varied across studies.…”

“…5 studies limited their analysis to those who completed follow-up [16, 30, 35, 37, 44] and 3 studies considered those who discontinued cART for a variety of reasons and/or lacked follow-up laboratory data as treatment failures [21, 26, 27]. While most studies did not describe how they handled patients who switched cART regimens, one excluded patients who stopped or changed cART during follow-up [18], three explicitly retained patients who switched [24, 30, 40], and one did a sensitivity analysis considering those who discontinued stavudine as treatment failures [27].…”

“…Manosuthi et al (2006, 2008, 2010) also reported low suppression among Thai patients: 69% at 6 months [39], 59% at 33 months [26] and 51% at 48 months [27]. Three other studies reported suppression rates between 64 and 70% [16, 21, 32]. However, three of these studies that reported low suppression rates considered those who discontinued cART or lacked follow-up laboratory data as treatment failures [21, 26, 27].…”

Durable Suppression of HIV-1 after Virologic Monitoring-Based Antiretroviral Adherence Counseling in Rakai, Uganda

“…The best indicator of adherence and response to treatment is the virologic response [ 12 ]. Accordingly, the World Health Organization (WHO) and many national AIDS control programs have adopted guidelines recommending viral load testing 3 to 6 months after initiating ART and then at regular intervals thereafter [ 13 ].…”