Objectives
To assess whether T cell activation independently predicts the extent of CD4+ T cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART).
Design
Prospective cohort study
Methods
HIV-infected adults starting ART and achieving a plasma HIV RNA level (VL) <400 copies/ml by month 6 were sampled from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort in Mbarara, Uganda. CD4 count, VL, and the % activated (CD38+HLA-DR+) T cells were measured every 3 months.
Results
Of 451 HIV-infected Ugandans starting ART, most were women (70%) with median pre-ART values: age, 34 years; CD4 count, 135 cells/mm3; and VL, 5.1 log10 copies/ml. Of these, 93% achieved a VL<400 c/ml by month 6 and were followed for a median of 24 months, with 8% lost to follow up at 3 years. Higher pre-ART CD8+ T cell activation was associated with diminished CD4 recovery after year 1, after adjustment for pre-ART CD4 count, VL, and gender (P=0.017). Thirty-four participants died, 15 after month 6. Each 10 percentage-point increase in activated CD8+ T cells at month 6 of suppressive ART was associated with a 1.6-fold increased hazard of subsequent death after adjusting for pre-therapy CD4 count (P=0.048).
Conclusions
Higher pre-ART CD8+ T cell activation independently predicts slower CD4+ T cell recovery and higher persistent CD8+ T cell activation during ART-mediated viral suppression independently predicts increased mortality among HIV-infected Ugandans. Novel therapeutic strategies aimed at preventing or reversing immune activation during ART are needed in this setting.
The kynurenine pathway of tryptophan catabolism independently predicts poor CD4(+) T-cell count recovery and increased mortality among HIV-infected Ugandans initiating ART and may be an important target for interventions.
This study of traditional healers and formal health workers determined their knowledge and practices in the field of HIV/AIDS and examined their training needs and attitudes to collaboration, in preparation for planning joint training workshops. Several misconceptions concerning symptoms and transmission of HIV disease were found in both groups, particularly among traditional healers. Twenty healers (51%) and four formal health workers (15%) claimed a cure existed for AIDS. The majority of traditional healers interviewed expressed difficulties discussing a diagnosis of HIV directly with patients, mainly due to fear of the patient becoming depressed and suicidal. Most interviewees wanted more training--the majority of traditional healers in recognizing symptoms of HIV/AIDS and their treatment, and the majority of formal health workers in HIV counselling. Most were interested in supplying condoms. Almost all healers and half of the formal health workers were keen to collaborate in training and patient care. The study indicates that there is willingness amongst Zambian traditional healers and formal health workers to collaborate in training and patient care in the field of HIV/AIDS. As well as covering symptoms, transmission and prevention of HIV/AIDS, training should aim to increase ability to openly discuss HIV with patients, which many traditional healers and some formal health workers find difficult. Involving traditional healers in supplying condoms may improve acceptability and availability, particularly in rural areas.
Alluvial deposits of the St Maughans Formation (Lower Old Red Sandstone, Early Devonian) of Tredomen Quarry, near Brecon, southeast Wales, have yielded the oldest known trails of swimming fish as well as body fossils of heterostracans and osteostracans, their inferred producers. Undichna unisulca comprises a single sinusoidal wave (of varying amplitude and wavelength) and is attributed to the caudal lobe or fin of a swimming heterostracan or osteostracan. Variation in the dimensions of U. unisulca trails, together with functional analysis of their inferred producers, suggests different fish sizes and swimming speeds. Undichna cf. simplicitas shows a more complex arrangement of intertwined waves and is interpreted as being produced by a combination of the caudal fin, anal spine and paired pelvic spines of an acanthodian. A new ichnotaxon, Undichna trisulcata isp. nov., consists of three isolated furrows arranged in parallel with associated pectoral fin imprints, and is interpreted as either the trail left by a 'cruising' cephalaspid, intermittently pushing off the substrate with its pectoral fins, or a trail made by a cephalaspid landing on the substrate. The presence of Undichna within these relatively proximal fluvial sediments (displaying no evidence of marine influence) is indicative of an in situ vertebrate freshwater community. Taphonomic constraints on Undichna preservation, in combination with sedimentological analysis, suggest weak bottom currents and/or rapid burial, post-trail formation. Arthropod trackways (Diplichnites gouldi Types A and B, Protichnites isp., and Palmichnium pottsae), a bilobed trail (cf. Cruziana), worm burrows (cf. Cochlichnus) and large meniscate backfilled burrows (Beaconites barretti) contribute invertebrate components to this ichnofauna. The association of Diplichnites trackways on the same surfaces as Undichna supports a semi-aquatic habit of their inferred myriapod producers.
Clinical presentation with ICH was associated with EA aneurysms, but the association was due to aneurysmal rather than BAVM rupture, suggesting that EAs and the BAVM ICH risks may be considered as separate entities in future studies.
Few reports have examined the impact of HIV-1 transmitted drug resistance (TDR) in resource-limited settings where there are fewer regimen choices and limited pretherapy/posttherapy resistance testing. In this study, we examined TDR prevalence in Kampala and Mbarara, Uganda and assessed its virologic consequences after antiretroviral therapy initiation. We sequenced the HIV-1 protease/reverse transcriptase from n = 81 and n = 491 treatment-naive participants of the Uganda AIDS Rural Treatment Outcomes (UARTO) pilot study in Kampala (AMU 2002(AMU -2004 and main cohort in Mbarara (MBA 2005(MBA -2010. TDR-associated mutations were defined by the WHO 2009 surveillance mutation list. Posttreatment viral load data were available for both populations. Overall TDR prevalence was 7% (Kampala) and 3% (Mbarara) with no significant time trend. There was a slight but statistically nonsignificant trend indicating that the presence of TDR was associated with a worse treatment outcome. Virologic suppression (£ 400 copies/ml within 6 months posttherapy initiation) was achieved in 87% and 96% of participants with wildtype viruses versus 67% and 83% of participants with TDR (AMU, MBA p = 0.2 and 0.1); time to suppression (log-rank p = 0.3 and p = 0.05). Overall, 85% and 96% of study participants achieved suppression regardless of TDR status. Surprisingly, among the TDR cases, approximately half still achieved suppression; the presence of pretherapy K103N while on nevirapine and fewer active drugs in the first regimen were most often observed with failures. The majority of patients benefited from the local HIV care system even without resistance monitoring. Overall, TDR prevalence was relatively low and its presence did not always imply treatment failure.
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