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Articles by M. S Saag
Total Records ( 2 ) for M. S Saag
  B. H Chi , L. B Mulenga , A Mwango , A Mwinga , M Bulterys and M. S Saag

Background High-level adherence to antiretroviral therapy (ART) is associated with favourable patient outcomes. In resource-constrained settings, however, there are few validated measures. We examined the correlation between clinical outcomes and the medication possession ratio (MPR), a pharmacy-based measure of adherence.

Methods We analysed data from a large programmatic cohort across 18 primary care centres providing ART in Lusaka, Zambia. Patients were stratified into three categories based on MPR-calculated adherence over the first 12 months: optimal (≥95%), suboptimal (80–94%) and poor (<80%).

Results Overall, 27 115 treatment-naïve adults initiated and continued ART for ≥12 months: 17 060 (62.9%) demonstrated optimal adherence, 7682 (28.3%) had suboptimal adherence and 2373 (8.8%) had poor adherence. When compared with those with optimal adherence, post-12-month mortality risk was similar among patients with sub-optimal adherence [adjusted hazard ratio (AHR) = 1.0; 95% CI: 0.9–1.2] but higher in patients with poor adherence (AHR = 1.7; 95% CI: 1.4–2.2). Those <80% MPR also appeared to have an attenuated CD4 response at 18 months (185 cells/µl vs 217 cells/µl; P < 0.001), 24 months (213 cells/µl vs 246 cells/µl; P < 0.001), 30 months (226 cells/µl vs 261 cells/µl; P < 0.001) and 36 months (245 cells/µl vs 275 cells/µl; P < 0.01) when compared with those above this threshold.

Conclusions MPR was predictive of clinical outcomes and immunologic response in this large public sector antiretroviral treatment program. This marker may have a role in guiding programmatic monitoring and clinical care in resource-constrained settings.

  J. F Salazar Gonzalez , M. G Salazar , B. F Keele , G. H Learn , E. E Giorgi , H Li , J. M Decker , S Wang , J Baalwa , M. H Kraus , N. F Parrish , K. S Shaw , M. B Guffey , K. J Bar , K. L Davis , C Ochsenbauer Jambor , J. C Kappes , M. S Saag , M. S Cohen , J Mulenga , C. A Derdeyn , S Allen , E Hunter , M Markowitz , P Hraber , A. S Perelson , T Bhattacharya , B. F Haynes , B. T Korber , B. H Hahn and G. M. Shaw

Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4+ T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12–20 mo, viruses exhibited concentrated mutations at 17–34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses.

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