CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

161 The Impact of Antiretroviral Therapy on Adult Life Expectancy in Sub-Saharan Africa Georges Reniers 8 ; Jeffrey Eaton 1 ; Jessica Nakiyingi-Miiro 2 ; Amelia C. Crampin 4 ; Chodziwadziwa Kabudula 5 ; Kobus Herbst 3 ; Mark Urassa 6 ; Amek Nyaguara 7 ; Emma Slaymaker 8 ALPHA Network

1 Imperial College London, London, United Kingdom; 2 MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda; 3 Africa Centre for Health and Population Studies, Mtubatuba, South Africa; 4 Karonga Prevention Study, Chilumba, Malawi; 5 University of the Witwatersrand, Johannesburg, South Africa; 6 National Institute for Medical Research, Mwanza, United Republic of Tanzania; 7 Kenya Medical Research Institute-Centers for Disease Control, Kisumu, Kenya; 8 London School of Hygiene and Tropical Medicine, London, United Kingdom Background: Few studies directly measure the population-wide impact of antiretroviral therapy (ART) on adult mortality, with most existing estimates relying on extrapolations from ART coverage. We use demographic surveillance data from seven study sites in six eastern and southern African countries to estimate (i) gross adult life expectancy (LE) gains since the introduction of ART, (ii) net LE gains attributable to ART, and (iii) the remaining LE deficit due to HIV. Methods: We use non-parametric survival analysis for estimating the LE of adults aged 15 years and above. The gross LE gain is defined as the difference in the overall LE between two calendar years; the current LE deficit due to HIV is the difference in the LE of HIV negatives and the LE for the population as a whole. Net LE gains attributable to ART are obtained by fitting a model of age-specific HIV incidence and survival to estimate the counterfactual LE in the absence of ART. Estimates are presented for the years 2000 to 2012, and disaggregated by sex and study site. Results: The pooled dataset contains 655,227 adults, contributing over 3 million person-years of follow up time and 46,898 deaths. Gross adult LE gains range from 8 to 20 years (Figure 1); net LE increases attributable to ART are between 4 and 19 years. Gross LE gains are largest in eastern Africa, where mortality reductions also benefited from historical declines in HIV incidence, but the effect of ART (net LE gains) is largest in South Africa, where LE would have continued to decline without ART. The current LE deficit is around 10 years in sites with the highest HIV prevalence (Kisumu and uMkhanyakude); in other sites the LE deficit is now under 5 years (Figure 1). On average, women have gained 3.4 more adult life-years than men, but their current LE deficit is still between 0.6 and 5.4 years larger.

Oral Abstracts

Conclusions: Gross adult LE gains between 10 and 15 years are norm and driven by the expansion of treatment, and in the eastern African study sites also by prior declines in HIV incidence. Large LE deficits due to HIV remain, however, and are indicative of the need for enhancing program coverage and impact. Women have generally gained more life-years than men, and that is due to gender differences in the uptake of services and treatment outcomes, women’s younger ages at infection, and women’s lower background mortality. Despite larger LE gains to date, women still lose more life-years to HIV than men. Session O-14 Oral Abstracts Room 613 10:00 am– 12:15 pm Immune Mechanisms: The Road to Protection 162 Passively Acquired ADCC Activity in HIV-Infected Infants Correlates With Survival Caitlin Milligan 1 ; Barbra A. Richardson 1 ; Grace John-Stewart 2 ; RuthW. Nduati 3 ; Julie M. Overbaugh 1 1 Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, US; 2 University of Washington, Seattle, WA, US; 3 University of Nairobi, Nairobi, Kenya Background: Antibody-dependent cellular cytotoxicity (ADCC) activity has been described as a potential immune correlate of protection from HIV infection in macaques and humans. The role of ADCC activity mediated by passively acquired antibodies (Abs) in HIV-exposed infants is unknown and was examined to determine if pre-existing HIV-specific antibodies provide protection from infection and/or disease progression. Methods: We evaluated the ADCC activity of passively acquired Abs in the first week of life from infants of HIV-positive mothers. Infants were included based on the following criteria: HIV-RNA negative at birth, breastfed ≥ 3 months, ≥ 6 months follow-up of negative infants. Seventy-two infants were included, 21 of who were first detected as HIV positive after birth. Infant plasmas were tested against an infant-derived, subtype A envelope using a rapid fluorometric ADCC assay. HIV-specific IgG1 was measured by binding to gp120 coated target cells and quantified by flow cytometry. IgG3 HIV-specific Ab titers were measured by ELISA. Comparisons of measurements in infected and uninfected infants were made by 2-sided Welch’s t-test. Survival analyses were conducted using Cox-proportional hazards models. Spearman’s rank correlation was used for correlation analyses. Results: Passively acquired ADCC activity was higher in uninfected infants than infected infants, but was not statistically significant (p=0.12). In infected infants, pre-existing ADCC activity was associated with increased survival: each 10% increase in ADCC activity was associated with a 49.1% reduction in the risk of mortality (p=0.03). ADCC activity positively correlated with the magnitude of HIV-specific IgG1 surface binding, measured as log 2 MFI(r=0.92, p<0.0001). The magnitude of surface IgG1 binding was also associated with survival in infected infants (HR:0.24, p=0.005). IgG3 binding Ab end point titers were not associated with infant infection (p=0.25) or survival (p=0.63). In measurements of longitudinal ADCC activity from 6 infected infants, passively acquired ADCC activity declined to undetectable levels prior to an increase in de novo responses. De novo ADCC responses did not correlate with passively acquired responses (r=-0.14, p=0.79).

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CROI 2015