HIV This Week

Ofori-Mante JA, Kaul A, Rigaud M, Fidelia A, Rochford G, Krasinski K, Chandwani S, Borkowsky W. Natural history of HIV infected pediatric long-term or slow progressor population after the first decade of life. Pediatr Infect Dis J 2007 Mar;26(3):217-20.

Perinatally infected long-term non-progressors/slow progressors represent a select group of individuals. There is very limited information on this group of children beyond the first decade of life. A group of HIV-infected long-term non-progressor/slow progressor children was studied. Ofori-Mante and colleagues enrolled 20 HIV-infected adolescents who were receiving no or minimal therapy (defined as single or dual nucleoside therapy) before the age of 10 years and who had maintained CD4 counts above 25% for the first decade of life. The authors analyzed immunologic and virologic characteristics. Thymic receptor excision circles (TREC) were measured on stored frozen peripheral blood mononuclear cells. CD4 count, viral load and other pertinent information including race and age were obtained from individual medical records. The results revealed that nine of the 20 patients recruited were noted to have developed falling CD4 counts at or around puberty, whereas the other 11 remained stable. There was no difference in TREC values or HIV RNA values before or after puberty between the 2 groups of patients. Those who remained stable, in terms of maintaining CD4 T cells as a group had falling viral loads with age. Those whose CD4 values declined after puberty had viral loads that did not decrease with age. The authors conclude that a select group of patients who never received HAART during their first decade of life will continue to maintain good CD4 associated with declining HIV RNA values. Thymic output is not predictive of those that don’t maintain CD4 T cells.

Editors’ note: How do the immune defences, in this select group of adolescents infected at birth, work to maintain CD4 count levels and produce falling viral loads with age? Answering this question could take us a long way along the path to understanding HIV immunology – and, for that matter, immunology in general.

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Chun TW, Justement JS, Moir S, Hallahan CW, Maenza J, Mullins JI, Collier AC, Corey L, Fauci AS. Decay of the HIV Reservoir in Patients Receiving Antiretroviral Therapy for Extended Periods: Implications for Eradication of Virus. J Infect Dis 2007 Jun 15;195(12):1762-4.

The persistence of latently infected resting CD4(+) T cells has been clearly demonstrated in human immunodeficiency virus (HIV)-infected individuals receiving effective antiviral therapy. However, estimates of the half-life of this viral reservoir have been quite divergent. Chun and colleagues demonstrate clear evidence for decay of this HIV reservoir in patients who initiated antiviral therapy early in infection. The half-life of this latent viral reservoir was estimated to be 4.6 months. It is projected that it will take up to 7.7 years of continuous therapy to completely eliminate latently infected resting CD4(+) T cells in infected individuals who initiate antiviral therapy early in HIV infection.

Editors’ note: The idea that early treatment could eventually eliminate latently infected CD4 cells is not new but remains to be proven. In the meantime, long term commitment both by individuals to adhere to treatment and by governments and development partners to ensure sustained access to antiretroviral treatment programmes is essential.

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Jones LE, Perelson AS. Transient Viremia, Plasma Viral Load, and Reservoir Replenishment in HIV-Infected Patients on Antiretroviral Therapy. J Acquir Immune Defic Syndr 2007 Aug 15; 45(5):483-93

When antiretroviral therapy (ART) is administered for long periods to HIV-1-infected patients, most achieve viral loads that are « undetectable » by standard assay methods (ie, HIV-1 RNA <50 copies/mL). Despite sustaining viral loads lower than the level of detection, a number of patients experience unexplained episodes of transient viremia or viral « blips. » Jone and Perelson propose that transient activation of the immune system by infectious agents may explain these episodes of viremia. Using 2 different mathematical models, one in which blips arise because of target cell activation and subsequent infection and another in which latent cell activation generates blips, the authors establish a nonlinear (power law) relationship between blip amplitude and viral load (under ART) that suggest blips should be of lower amplitude, and thus harder to detect, as increasingly potent therapy is used. This effect can be more profound than is predicted by simply lowering the baseline viral load from which blips originate. Finally, the authors suggest that sporadic immune activation may elevate the level of chronically infected cells and replenish viral reservoirs, including the latent cell reservoir, providing a mechanism for recurrent viral blips and low levels of viremia under ART.

Editors’ note: Intercurrent infections such as colds, flu, and herpes simplex and other sexually transmitted infections in all people tend to activate the immune system transiently to mount a defence. In people living with HIV this immune activation leads to transient HIV viraemia which may replenish viral reservoirs. If the goal is to deplete HIV’s reservoirs, then where possible, people living with HIV should take steps to prevent other infections (hand washing, flu shots, safer sex and rapid treatment of sexually transmitted infections) which may replenish the reservoirs.