THLBB1: Late Breakers- Track B-1

THLBB0101: Quadrivalent HPV vaccine efficacy against HPV 6/11/16/18 infection and disease in men, H. Jensen, Germany.

Jensen et al. presented the results of protocol 020, an RCT of the HPV vaccine Gardasil. This was a very important study with impressive results. This involved >4000 patients (who had to be HIV-negative, HPV seronegative, HPV PCR negative, without lesions and with <6 sexual partners) in 18 countries, and had approximately 2 years of follow up time on average. Key results were: 1) 90% efficacy in preventing extra-genital HPV lesions (95%CI 69-98), 89% efficacy in preventing condyloma, 75% efficacy in preventing high grade anal intra-epithelial neoplasia (AIN 2 or more), 78% efficacy in preventing a combined endpoint of AIN or anal cancer over all, and 86% efficacy against “persistent infection” (defined by positive DNA PCR on 2 samples 4 months apart). A key critique was that since the study observed zero cases anal cancer, it could not say Gardasil is efficacious in preventing anal cancer (but 10 more years of observation is planned for these patients).

THLBB0102: Post-18 month confirmatory HIV testing in HIV DNA PCR positive children: retrospective descriptive analysis from an operational setting in Lesotho, A. Garcia-Prats, Tanzania.

This study investigated the test characteristics of confirmatory HIV antibody testing in infants >18 months old who had previously been diagnosed with HIV as infants via HIV DNA PCR. Infants with a positive DNA PCR done while <18 months old, as well as two rapid antibody tests done while >18 months old, were studied. Authors found that of the 27 kids with discordant results on the two rapid Ab tests, 10 were definitely positive for HIV. And of the 22 kids with both rapid antibody tests negative, 17 were definitely positive for HIV. This emphasizes the inadequacy of performing double rapid antibody tests to classify HIV status after 18 months. Furthermore, 2 infants who had had positive PCR were found to be negative, emphasizing that one should not rely on a single DNA PCR to establish HIV positivity.

THLBB0103: The cost of early vs. deferred pediatric antiretroviral treatment in South Africa – a comparative economic analysis of the first year of the CHER trial, G. Meyer-Rath, USA.

This elegant study analyzed costs of care for children who started ART early versus late (the two arms of the previously reported CHER trial [which showed a dramatic mortality benefit to early treatment]), and included a third group of kids who were not in the CHER trial but who received routine care in Johannesburg. It found the costs of care over the first year of life to be: early TX: $1349, later TX: $2432, routine care: $2908. The fraction of these costs due to inpatient hospital care for the three arms were, respectively, 26%, 51%, and 84%. Thus, giving infants early ART not only reduces overall costs, but causes far less inpatient care cost to be incurred. This was not a “modeling” study, but rather an analysis of actual costs incurred via a chart review. This is a clear, concise, and highly compelling study that strongly advocates for early treatment of all infants.

THLBB0104: PENPACT-1 (PENTA9/PACTG390): a randomized trial of PI vs. NNTRI combination ART regimens and viral load treatment switching strategies in HIV-1 infected ART-naïve children age>30 days and <18 years, A. Melvin, USA.

Melvin et al. presented this 2x2 factorial design clinical trial testing 1) whether a PI vs. NNRTI regimen was better for treating ART-naïve children, and 2) whether declaring virologic failure and switching to second line ART should be done at a VL of 1,000 vs. 30,000. Follow-up time was 4 years, and n=roughly 250. Primary outcome was the level of VL decrease from baseline to 4-year follow-up. There was no difference in this outcome between NNRTI and PI regimens, but the VL 1,000 cutoff group switched approximately one year earlier than the VL 30,000 cutoff group. The children did well, with >80% having VL<500 at 4y follow-up, and achiving good CD4 rises. This study strongly supports pediatric ART, and states that PI and NNRTI therapies had equal efficacy in this trial.

THLBB0105: Impact of triple-ARV prophylaxis during pregnancy and breastfeeding compared with short-ARV prophylaxis to prevent MTCT on maternal disease progression: the Kesho Bora RCT in Burkina Faso, Kenya and South Africa (title abbreviated), T. Farley, Switzerland.

Farley et al. detailed results from a study that compared giving pregnant women 3-drug ART pre-delivery to the end of breastfeeding vs. giving them just AZT through delivery followed by sdNVP. They then examined CD4 count progression after delivery, and not surprisingly to be shorter in the women given 3-drug ART. They next examined CD4 count progression in the two arms, counting time zero as the moment prophylaxis was stopped, and here found no difference in progression. A key question raised by the audience was the lack of comparison to a group who had continued ART throughout. The study advocates strongly for ART for pregnant women.

THLBB0106: Significant enhancement in survival with early (2 weeks) vs. late (8 weeks) initiation of HAART in severely immunosuppressed HIV-infected adults with newly diagnosed tuberculosis, F. Blanc, France.

Blanc et al. presented the highly significant results of the landmark CAMELIA trial that examined a very sick group of patients diagnosed with HIV/TB (median CD4 25, all pts had CD4<200, most with pulmonary or pulmonary+extrapulmonary TB). Patients (n=661) were started on standard TB therapy, randomized to also begin ART at either 2 weeks or 8 weeks of TB therapy. Patients starting early (2 weeks) ART had much higher probabilities of surviving to 50, 100 and 150 weeks than patients who started ART at 8 weeks. The hazard ratio for death with late treatment, even after controlling for various other factors like drug resistant TB, low BMI and low Karnofsky score, remained 1.52, highly significant. While IRIS to TB was almost three-fold higher incidence in the early treatment group, it was always easily treated. Authors and audience agreed that this and prior studies strongly advocate for early ART in patients receiving TB therapy, and should help eliminate TB IRIS as a potential barrier to initiating ART, as it appears to be clinically manageable, and the mortality benefit appears to be dramatic.

THLBB107 Early initiation of antiretroviral therapy and associated reduction in mortality, loss to follow-up and hospitalization in a routine programme in Lesotho

Ford, et al. compared mortality, morbidity and loss to follow-up rates in Lesotho from clinical data collected from 2001-2009. In 2008, Lesotho changed their national guidelines to initiation of ART at CD4<350. He compared baseline characteristics and outcomes in patients initiating ART with CD4≤200 vs. >200. Median CD4 count at ART initiation was 111 in the late ART (CD4≤200) group vs. 280 in the early ART group, and the proportion with active TB in the late ART group (24%) was significantly higher than in the early ART group (10.3%, p<0.001). Mortality, loss to follow-up, morbidity and frequency of hospitalization were significantly lower in the early ART group compared to the late ART group. These findings provide further evidence to support the feasibility and benefit of early ART initiation in resource-limited settings.

THLBB108 Impact of transmitted drug resistance (TDR) on virological and immunological response to initial combination antiretroviral therapy (cART) – EuroCoord-CHAIN joint project

Wittkop, et al. analyzed virologic failure by three strata of transmitted drug resistance (based on a pre-treatment genotype) using pooled data from 25 cohorts. 953 (9%) of the subjects had TDR. Patients with resistance to at least one drug in their ART regimen were significantly more likely to experience virologic failure compared to those with no drug resistance mutations. In the presence of TDR and when a fully active ART regimen was used, there was a higher risk of virologic failure in patients on NNRTIs compared to boosted PIs. Investigators speculated that this was due to undetected minority drug resistant mutations that affect NNRTI efficacy when TDR is present.

THLBB109 Nadir CD4 is a predictor of HIV neurocognitive impairment (NCI) in the era of combination antiretroviral therapy (cART): results from the CHARTER study

Grant, et al. found a significant association between nadir CD4 count (by clinical record or self-report) and neurocognitive impairment (NCI), with greater NCI among patients with lower CD4 nadirs. Even in the subset of patients on ART with undetectable viral loads at the time of analysis, lower CD4 nadir remained associated with greater NCI. Grant hypothesized that CD4 nadir may represent a neurologic “legacy event” that contributes substantially to HIV-related brain injury and NCI.