Long-term CD4+ lymphocyte response following HAART initiation in a U.S. Military prospective cohort

<p>Abstract</p> <p>Background</p> <p>Among HIV-infected persons initiating highly active antiretroviral therapy (HAART), early CD4+ lymphocyte count increases are well described. However, whether CD4+ levels continue to increase or plateau after 4-6 years is controversial.</p> <p>Methods</p> <p>To address this question and identify other determinants of CD4+ response, we analyzed data for 1,846 persons from a prospective HIV military cohort study who initiated HAART, who had post-HAART CD4+ measurements, and for whom HIV seroconversion (SC) date was estimated.</p> <p>Results</p> <p>CD4+ count at HAART initiation was ≤ 200 cells/mm³for 23%, 201-349 for 31%, 350-499 for 27%, and ≥500 for 19%. The first 6 months post-HAART, the greatest CD4+ increases (93-151 cells) occurred, with lesser increases (22-36 cells/year) through the first four years. Although CD4+ changes for the entire cohort were relatively flat thereafter, HIV viral load (VL) suppressors showed continued increases of 12-16 cells/year. In multivariate analysis adjusting for baseline CD4+ and post-HAART time interval, CD4+ responses were poorer in those with: longer time from HIV SC to HAART start, lower pre-HAART CD4+ nadir, higher pre-HAART VL, and clinical AIDS before HAART (P < 0.05).</p> <p>Conclusions</p> <p>Small but positive long-term increases in CD4+ count in virally suppressed patients were observed. CD4+ response to HAART is influenced by multiple factors including duration of preceding HIV infection, and optimized if treatment is started with virally suppressive therapy as early as possible.</p

CD8+ Lymphocytes Control Viral Replication in SIVmac239-Infected Rhesus Macaques without Decreasing the Lifespan of Productively Infected Cells

While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are 500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

HIV/AIDS stigma-associated attitudes in a rural Ethiopian community: characteristics, correlation with HIV knowledge and other factors, and implications for community intervention

Abstract Background Whether scale-up of HIV prevention and care will reduce negative attitudes and discriminatory practices towards persons living with HIV/AIDS (PLWH) is uncertain. An HIV knowledge and attitude survey was conducted in a rural Ethiopian community where HIV prevention and treatment was being rapidly scaled up. Data were analyzed to identify prevalence of and factors associated with stigma-associated attitudes towards PLWH. Methods We surveyed 561 adults from 250 randomly selected households in the rural town of Arba Minch and surrounding villages about positive or negative attitudes towards PLWH, as well as demographic characteristics, and knowledge about HIV transmission and treatment. Results Eighty percent of respondents agreed with ≥ 1 negative statements indicating blame or shame towards PLWH and 41% agreed with ≥ 1 negative statements associated with distancing themselves from PLWH. However, only 14% expressed negative responses about whether PLWH should receive support from their communities. In multivariate analysis, a greater number of negative attitudes towards PLWH was significantly (p  Conclusions In a rural Ethiopian setting in which rapid scale-up of HIV treatment occurred, many respondents still characterized HIV as associated with shame or blame, or indicated PLWH would be isolated or discriminated against. HIV stigma can hamper both prevention and treatment programs. We identified multiple issues which, if addressed, can help promote a more positive cycle in which PLWH are appreciated as members of one’s own community who are affirmatively interacted with and supported. Stigma reduction programs should address knowledge gaps such as fears of casual contact contagion, and lack of awareness of medical interventions to help prevent HIV disease, as well as building upon community-based attitudes of the importance of supporting and showing compassion for PLWH.</p