Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells

Abstract

Latent HIV-1 persists in resting memory CD4+ T cells, even in patients receiving highly active antiretroviral therapy (HAART). It has been unclear how stable this latent reservoir is and whether its persistence reflects replenishment by low-level viremia. Here we show that even in treated patients who have had no detectable viremia for as long as 7 years, the reservoir decays so slowly (t(1/2) = 44 months) that eradication is unlikely.

Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy

“…At present, the cellular origin and virological character of these elevations in CSF HIV RNA remain undefined, whether bursts of viruses from trafficking cells or signs that a CNS reservoir in macrophages or other cells periodically can produce HIV [47]. However, they are clearly different from neuro-symptomatic escape discussed next: clinically, in their lack of symptoms, signs, or discernable neurological deterioration, and biologically, in their lack of apparent cellular inflammatory response (Table 1).…”

Dendritic cell based vaccines for HIV infection

“…Although combined antiretroviral therapy (cART) has proven to be highly effective to prevent clinical progression and death, by itself it is unable to eradicate the infection, thus necessitating therapy throughout life. 1,2 Resistance, adverse effects in the medium-long-term, and cost are important limitations for lifelong adherence to this therapy. Although the number of HIV infected patients on treatment in developing countries has increased steadily in the last few years and it has been associated with a decrease of new HIV infections, the treatment demands rise.…”

Stable gene expression occurs from a minority of integrated HIV-1-based vectors: transcriptional silencing is present in the majority

“…In patients undergoing antiretroviral therapy, after the rapid initial decline in viraemia, the level of detectable cell associated virus decays with a very long half-life estimated to be over 44 months. 4,5 It is possible to culture latently infected cells in vitro. 6 Genetic studies have shown drug-sensitive archival HIV-1 sequences can be found in T cells in patients who have undergone antiretroviral therapy for up to 5 years.…”