This feature highlights some of the studies that emerged from the 2011 CROI annual conference, including the protective effects of circumcision against HIV, treatment of HIV-tuberculosis coinfection, and research on HIV-resistant T cells.
The Particulars: Previous research has suggested that circumcising men may help protect them in the future from contracting the HIV virus. Findings from recent original randomized trials have suggested that circumcision reduces the risk of catching HIV by about 50%. Clinicians have expressed some concern about the effect of male circumcision on changing sexual behaviors and the adoption of more risk practices. A study was conducted to see how circumcision affects both the risk of HIV and human behavior.
Data Breakdown:Researchers found that HIV incidence was 73% lower among trial participants who were circumcised and those who got circumcised later when compared with those in a control arm who did not accept circumcision. Researchers offered men in the control arm the chance to be circumcised, and 80.4% accepted. Among control participants who were circumcised, the risk of HIV was reduced 67%, compared with the men who declined the procedure. In post-trial surveillance, the study group observed no change in the number of non-marital sex partners between intervention and control patients. There was also no significant difference in condom use between the 1,321 men who got circumcised and the 372 who did not.
Take Home Pearls: The benefit of male circumcision for HIV prevention appears to persist, even long after the procedure is administered. Circumcision does not appear to induce men to change their sexual behavior in risky ways.
Prompt Treatment Needed for HIV-TB Coinfection [back to top]
The Particulars: According to the CDC, tuberculosis (TB) remains a serious threat for HIV-infected people. Coinfected individuals are at greater risk for shortened lifespan and for developing active TB disease. Little is known about the effect of early and delayed treatment of HIV while TB therapy is initiated. A study was performed to determine the effect of timing of HIV and TB therapy on the development of AIDS-defining events or death.
Data Breakdown: In an open-label trial that was conducted in 285 patients with CD4+ counts of 50 cells/mm3 or less, 15.5% of patients who were started immediately on antiretroviral therapy experienced an AIDS-defining event or death, compared with 26.6% of the those for whom treatment was delayed. However, patients with higher CD4+ cell levels may be able to delay HIV therapy while undergoing initial therapy for TB. Delays in treating HIV of about 95 days did not appear to increase the risks of developing AIDS or death. Immune reconstitution inflammatory syndrome (IRIS) was significantly higher with immediate antiretroviral therapy. IRIS was observed among 11% of the immediate-treatment patients, compared with 5% of patients treated later. No deaths were attributed to TB IRIS.
Take Home Pearls: HIV patients who present with low CD4+ cell counts and TB coinfection should be treated as soon as possible for both diseases. The findings highlight the need to develop consensus, user-friendly recommendations for the management of HIV-TB coinfected individuals.
Nurse Care Effective in HIV Management [back to top]
The Particulars: The epidemic of HIV in South Africa and the demand to initiate treatment are significant. The number of facilities to manage HIV in South Africa, however, is limited and costly for those who receive treatment. Antiretroviral therapy is sometimes initiated at a single institution, but patients are down-referred to other clinics to get care. Management shifting toward the use of nurses and other providers has been occurring in South Africa in an attempt to provide a good level of care at a lower cost and to relieve the pressure on the scarcity of doctors and highly trained clinicians.
Data Breakdown: Investigators analyzed 540 patients who were treated at down-referral facilities, while 1,620 patients remained in care at the site where antiretroviral treatment was initiated. Patients were eligible to participate in the study if they were on stable antiretroviral therapy for longer than 11 months, had an undetectable viral load in the prior 10 months, had CD4+ counts greater than 200 cells/mm3, had weight loss of less than 5% over the last three visits, and had no opportunistic infections. Among patients who were on a stable antiretroviral regimen, 98% of those assigned to a nurse-managed pilot program at a down-referral clinic were still in treatment and responding 1 year later. Conversely, just 93% of the patients who remained in care at the central clinic where treatment was initiated stayed in treatment. Costs were 9% to 10% lower at the down referral site.
Take Home Pearls: Patients with HIV whose antiretroviral therapy was managed by nurses at regional clinics in South Africa appear to do as well as those whose care was handled by physicians at larger hospitals. A down-referral strategy may increase treatment capacity and conserve resources without compromising patient outcomes. The reduction in costs and improvement in outcomes indicate that this is a cost-effective strategy for the maintenance of stable patients.
Optimism on HIV-Resistant T Cells [back to top]
The Particulars: : Interest in HIV-resistant T cells has increased over the past few years after the discovery that some people completely lack the CCR5 receptor and are therefore highly resistant to HIV. Initial infection with HIV usually uses this route. Researchers have conducted experiments in which CD4+ T cells have been taken from HIV patients, shipped to a laboratory where they were modified, and then returned and reinfused. The purpose of these experiments is to target the CCR5 receptor, one of the two major proteins used by HIV to enter its target CD4 cells.
Data Breakdown: In the study, patients underwent leukapheresis at an outpatient clinic, and the resulting samples were depleted of monocytes and CD8 cells while being enriched with CD4 cells. The samples were frozen and shipped to a laboratory. After the modification, they were re-frozen, shipped back, and reinfused. All six patients involved in the study had well-controlled HIV. The process was shown to disrupt the CCR5 gene in about 25% of the cells treated. No serious adverse events were reported, and 30 of 32 reported adverse events were mild, passed off quickly, and appeared to be related to the infusion process rather than the modified cells. By Day 14, there was a three-fold increase in the number of modified cells, compared with the number that was infused. After 90 days, the cells were increased, compared with the initial dose, both in plasma (60%) and in rectal tissue (70%). In three of five cases, the ratio of CD4 to CD8 cells was normalized.
Take Home Pearls: Preliminary data show that HIV-resistant T cells may be created in laboratories and returned to patients, possibly offering a new approach to therapy. The data are limited in that little is known on the efficacy of genetically modified cells at controlling HIV infection. Results of the study, however, suggest that the genetic modification process can be used on a large scale if it proves effective.
For more information on these items and other research that was presented at CROI 2011, go tohttp://retroconference.org/2011/.