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BackgroundNew strategies are needed to combat the high incidence of cervical cancer in resource-limited settings such as sub-Saharan Africa. Screening for high-risk human papillomavirus (hrHPV) DNA is sensitive for pre-cancer, but its lack of specificity results in substantial overtreatment in low resource settings where additional testing (e.g., colposcopy) is rarely available. Testing for hrHPV E6/E7 mRNA may enhance specificity, but little is known about its performance characteristics in resource-limited settings.MethodsIn a series of community health fairs in rural Uganda, women aged 25 to 49 years provided self-collected vaginal samples, which were tested for hrHPV (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) E6/E7 mRNA with the Aptima® assay. Positive specimens underwent testing for HPV-16 and 18/45. After excluding pregnant women, all women testing positive for any hrHPV subsequently were offered cervical biopsy to determine pathology.ResultsA total of 1892 women provided a vaginal sample for hrHPV testing during 24 health fairs. The median age was 34 years, HIV prevalence was 10, and 95% had not been previously screened. Prevalence of any hrHPV E6/E7 mRNA was 21% (95% confidence interval (CI): 19 to 23%); the prevalence of HPV-16 was 2.6%, HPV-18/45 1.9%, and HPV 16 and 18/45 were jointly found in 0.1% of the study population. Younger age, pregnancy and HIV-positivity were independently associated with any hrHPV infection. Of the 255 evaluable cervical biopsies, the positive predictive value of detecting any hrHPV E6/E7 mRNA for presence of cervical intraepithelial neoplasia grade 2 or higher ("CIN 2+") was 8.2% (95% CI: 5.1 to 12%). The positive predictive value associated with detection of HPV-16 mRNA (15%) or HPV-18/45 mRNA (15%) was only slightly higher.ConclusionAmong community-based women in Uganda, the prevalence of any hrHPV E6/E7 mRNA in vaginal samples was high, but the prevalence of the most oncogenic HPV types (16, 18, or 45) was substantially lower. Positive predictive value of hrHPV mRNA-positivity for CIN 2+ was also low, including when restricting to HPV 16/18/45-positivity. The findings emphasize the need to identify more specific screening approaches for cervical cancer.

Abstract Background Malaria is one of the most serious infectious diseases in the world. The malaria burden is greatly affected by human immunity, and immune responses vary between populations. Genetic diversity in KIR and HLA-C genes, which are important in immunity to infectious diseases, is likely to play a role in this heterogeneity. Several studies have shown that KIR and HLA-C genes influence the immune response to viral infections, but few studies have examined the role of KIR and HLA-C in malaria infection, and these have used low-resolution genotyping. The aim of this study was to determine whether genetic variation in KIR and their HLA-C ligands differ in Ugandan populations with historically varied malaria transmission intensity using more comprehensive genotyping approaches. Methods High throughput multiplex quantitative real-time PCR method was used to genotype KIR genetic variants and copy number variation and a high-throughput real-time PCR method was developed to genotype HLA-C1 and C2 allotypes for 1344 participants, aged 6 months to 10 years, enrolled from Ugandan populations with historically high (Tororo District), medium (Jinja District) and low (Kanungu District) malaria transmission intensity. Results The prevalence of KIR3DS1, KIR2DL5, KIR2DS5, and KIR2DS1 genes was significantly lower in populations from Kanungu compared to Tororo (7.6 vs 13.2%: p = 0.006, 57.2 vs 66.4%: p = 0.005, 33.2 vs 46.6%: p

Abstract Background Deep venous thrombosis (DVT) and its major complication pulmonary embolism (PE) are collectively known as venous thromboembolism. In Uganda, the prevalence of DVT among HIV patients has not been previously published. The aim of the study was to determine the prevalence and sonographic features of lower limb deep venous thrombosis among HIV positive patients on anti-retroviral treatment (ART). Methods This was a cross sectional study in which HIV positive patients on ART were recruited from an out-patient HIV clinic at Mulago National Referral Hospital. Patients were randomly selected and enrolled until a sample size of 384 was reached. Study participants underwent compression and Doppler ultrasound studies of both lower limb deep veins using Medison Sonoacer7 ultrasound machine. Resuts We found a prevalence of DVT of 9.1% (35 of 384 participants) among HIV patients on ART. The prevalence of latent (asymptomatic) DVT was 2.3%. Among 35 patients with DVT, 42.8% had chronic DVT; 31.1% had acute DVT and the rest had latent DVT. Among the risk factors, the odds of occurrence of DVT among patients with prolonged immobility were 4.81 times as high as in those with no prolonged immobility (p = 0.023; OR = 4.81; 95% CI 1.25–18.62). Treatment with second line anti-retroviral therapy (ART) including protease inhibitors (PIs) was associated with higher odds of DVT occurrence compared with first line ART (p = 0.020; OR = 2.38; 95% CI 1.14–4.97). The odds of DVT occurrence in patients with a lower CD4 count (

Objective. To describe the clinical decisions taken for patients failing on treatment and possible implementation leakages within the monitoring cascade at a large urban HIV Centre in Kampala, Uganda. Methods. As per internal clinic guidelines, VL results >1,000 copies/ml are flagged by a quality assurance officer and sent to the requesting clinician. The clinician fills a “decision form” choosing: (1) refer for adherence counselling, (2) repeat VL after 3 months, and (3) switch to second line. We performed data extraction on a random sample of 100 patients with VL test >1,000 copies/ml between January and August 2015. For each patient, we described the action taken by the clinicians. Results. Of 6,438 patients with VL performed, 1,021 (16%) had >1,000 copies/ml. Of the 100 (10.1%) clinical files sampled, 61% were female, median age was 39 years (IQR: 32–47), 81% were on 1st-line ART, 19% on 2nd-line, median CD4 count was 249 cells/µL (IQR: 145–390), median log10 VL 4.42 (IQR: 3.98–4.92). Doctors’ decisions were; refer for adherence counseling 49%, repeat VL for 25%, and switch to second line for 24% patients. Forty-one percent were not managed according to the guidelines. Of these, 29 (70.7%) were still active in care, 7 were tracked [5 (12.2%) lost to program, 2 (4.9%) dead] and 5 patients were not tracked. Conclusion. Despite the implementation of internal systems to manage patients failing ART, we found substantial leakages in the monitoring “cascade”. Additional measures and stronger clinical supervision are needed to make every test count, and to ensure appropriate management of patients failing on ART.

Introduction: The majority of studies from resource-limited settings only report short-term virological outcomes of patients on antiretroviral treatment (ART). We aim to describe the long-term durability of first-line ART and identify factors associated with long-term virological outcomes. Methods: At the Infectious Diseases Institute in Kampala, Uganda, 559 adult patients starting ART in 2004 were enrolled into a research cohort and monitored with viral load (VL) testing every six months for 10 years. We report the proportion and cumulative probability of 1) achieving virologic suppression (at least one VL 1000 copies/ml or one VL >5000, for those without a subsequent one); 3) treatment failure (not attaining virologic suppression or experiencing virologic failure). We used Cox regression methods to determine the characteristics associated with treatment failure. We included gender, baseline age, WHO stage, body mass index, CD4 count, propensity score for initial ART regimen, VL, time-dependent CD4 count and adherence. Results: Of the 559 patients enrolled, 472 (84.8%) had at least one VL (67 died, 13 were lost to follow-up, 4 transferred, 2 had no VL available); 73.6% started on d4T/3TC/nevirapine and 26.4% on AZT/3TC/efavirenz. Patients in the two groups had similar characteristics, except for the higher proportion of patients in WHO Stage 3/4 and higher VL in the efavirenz-based group. Four hundred thirty-nine (93%) patients achieved virologic suppression with a cumulative probability of 0.94 (confidence interval (CI): 0.92-0.96); 74/439 (16.9%) experienced virologic failure with a cumulative probability of 0.18 (CI: 0.15-0.22). In the multivariate analysis, initial d4T/3TC/nevirapine regimen (hazard ratio (HR): 3.02; CI: 3.02 (1.66-5.44, p < 0.001)) and baseline VL [greater than or equal to] 5 log10 copies/ml (HR: 2.29; CI: 1.29-4.04) were associated with treatment failures; patients of older age (HR: 0.87 per five-year increase; CI: 0.77-0.99), with adherence >95% (HR: 0.04; CI: 0.02-0.11) and with higher time-dependent CD4 count (HR: 0.94 per 50 cells/ml increase; CI: 0.92-0.99, p < 0.001) were less likely to experience treatment failure. Conclusions: The long-term virological outcomes from this cohort are promising and comparable to those from research-rich settings. Our results provide further evidence that efavirenz is associated with better virological outcomes. Keywords: antiretroviral treatment; treatments failure; long term outcomes., Introduction Access to life-saving antiretroviral treatment (ART) has rapidly expanded in resource-limited settings over the past decade [1]. The greatest increase in the number of HIV-positive patients receiving ART was [...]

Background: There is a high rate of lost to programme (LTP) in human immunodeficiency virus (HIV)-positive young adults transitioning from paediatric/adolescent to adult care. Methods: We describe and identify risk factors for LTP in all patients 18-23 y of age at the Infectious Diseases Institute (Kampala, Uganda) from 2010 to 2014. Results: A total of 260 of 907 young adults (28.6%) became LTP. Among those on antiretroviral treatment, 39.3% became LTP. We found that the only risk factor associated with LTP was being in World Health Organization stage 3 or 4. Conclusion: There is a need for tracing studies to evaluate the true vital status of LTP in this group. [ABSTRACT FROM AUTHOR]