BackgroundWe estimated rates of human immunodeficiency virus (HIV)–1 transmission per coital act in HIV-discordant couples by stage of infection in the index partner MethodsWe retrospectively ...identified 235 monogamous, HIV-discordant couples in a Ugandan population-based cohort. HIV transmission within pairs was confirmed by sequence analysis. Rates of transmission per coital act were estimated by the index partner’s stage of infection (recent seroconversion or prevalent or late-stage infection). The adjusted rate ratio of transmission per coital act was estimated by multivariate Poisson regression ResultsThe average rate of HIV transmission was 0.0082/coital act (95% confidence interval CI, 0.0039–0.0150) within ∼2.5 months after seroconversion of the index partner; 0.0015/coital act within 6–15 months after seroconversion of the index partner (95% CI, 0.0002–0.0055); 0.0007/coital act (95% CI, 0.0005–0.0010) among HIV-prevalent index partners; and 0.0028/coital act (95% CI, 0.0015–0.0041) 6–25 months before the death of the index partner. In adjusted models, early- and late-stage infection, higher HIV load, genital ulcer disease, and younger age of the index partner were significantly associated with higher rates of transmission ConclusionsThe rate of HIV transmission per coital act was highest during early-stage infection. This has implications for HIV prevention and for projecting the effects of antiretroviral treatment on HIV transmission
The probability of HIV-1 transmission per coital act in representative African populations is unknown. We aimed to calculate this probability overall, and to estimate how it is affected by various ...factors thought to influence infectivity.
174 monogamous couples, in which one partner was HIV-1 positive, were retrospectively identified from a population cohort in Rakai, Uganda. Frequency of intercourse and reliability of reporting within couples was assessed prospectively. HIV-1 seroconversion was determined in the uninfected partners, and HIV-1 viral load was measured in the infected partners. Adjusted rate ratios of transmission per coital act were estimated by Poisson regression. Probabilities of transmission per act were estimated by log-log binomial regression for quartiles of age and HIV-1 viral load, and for symptoms or diagnoses of sexually transmitted diseases (STDs) in the HIV-1-infected partners.
The mean frequency of intercourse was 8·9 per month, which declined with age and HIV-1 viral load. Members of couples reported similar frequencies of intercourse. The overall unadjusted probability of HIV-1 transmission per coital act was 0·0011 (95% CI 0·0008–0·0015). Transmission probabilities increased from 0·0001 per act at viral loads of less than 1700 copies/mL to 0·0023 per act at 38 500 copies/mL or more (p=0·002), and were 0·0041 with genital ulceration versus 0·0011 without (p=0·02). Transmission probabilities per act did not differ significantly by HIV-1 subtypes A and D, sex, STDs, or symptoms of discharge or dysuria in the HIV-1-positive partner.
Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act in this Ugandan population.
A large proportion of postgraduate students the world over complete a research thesis in partial fulfilment of their degree requirements. This study identified and evaluated support mechanisms for ...research generation and utilization for masters' students in health institutions of higher learning in Uganda. This was a self-administered cross-sectional survey using a modified self-assessment tool for research institutes (m-SATORI). Postgraduate students were randomly selected from four medical or public health Ugandan universities at Makerere, Mbarara, Nkozi and Mukono and asked to circle the most appropriate response on a Likert scale from 1, where the "situation was unfavourable and/or there was a need for an intervention", to 5, where the "situation was good or needed no intervention". These questions were asked under four domains: the research question; knowledge production, knowledge transfer and promoting use of evidence. Mean scores of individual questions and aggregate means under the four domains were computed and then compared to identify areas of strengths and gaps that required action. Most of the respondents returned their questionnaires, 185 of 258 (71.7%), and only 79 of these (42.7%) had their theses submitted for examination. The majority of the respondents were male (57.3%), married or cohabiting (58.4%), and were medical doctors (71.9%) from Makerere University (50.3%). The domain proposal development for postgraduate research project had the highest mean score of 3.53 out of the maximum 5. Three of the four domains scored below the mid-level domain score of 3, that is, the situation is neither favourable nor unfavourable. Areas requiring substantial improvements included priority-setting during research question identification, which had the lowest mean score of 2.12. This was followed by promoting use of postgraduate research products, tying at mean scores of 2.28 each. The domain knowledge transfer of postgraduate research products had an above-average mean score of 2.75. This study reports that existing research support mechanisms for postgraduate students in Uganda encourage access to supervisors and mentors during proposal development. Postgraduate students' engagement with research users was limited in priority-setting and knowledge transfer. Since supervisors and mentors views were not captured, future follow-on research could tackle this aspect.
HIV-1 infection expands large populations of late-stage differentiated CD8 T cells that may persist long after viral escape from TCR recognition. In this study, we investigated whether such CD8 T ...cell populations can perform unconventional innate-like antiviral effector functions. Chronic untreated HIV-1 infection was associated with elevated numbers of CD45RA
CD57
terminal effector CD8 T cells expressing FcγRIIIA (CD16). The FcγRIIIA
CD8 T cells displayed a distinctive transcriptional profile between conventional CD8 T cells and NK cells, characterized by high levels of
and low expression of
This transcriptional profile translated into a distinct NKp80
IL-7Rα
surface phenotype with high expression of the Helios transcription factor. Interestingly, the FcγRIIIA
CD8 T cells mediated HIV-specific Ab-dependent cellular cytotoxicity (ADCC) activity at levels comparable with NK cells on a per cell basis. The FcγRIIIA
CD8 T cells were highly activated in a manner that correlated positively with expansion of the CD8 T cell compartment and with plasma levels of soluble mediators of antiviral immunity and inflammation such as IP-10, TNF, IL-6, and TNFRII. The frequency of FcγRIIIA
CD8 T cells persisted as patients initiated suppressive antiretroviral therapy, although their activation levels declined. These data indicate that terminally differentiated effector CD8 T cells acquire enhanced innate cell-like characteristics during chronic viral infection and suggest that HIV-specific ADCC is a function CD8 T cells use to target HIV-infected cells. Furthermore, as the FcγRIIIA
CD8 T cells persist in treatment, they contribute significantly to the ADCC-capable effector cell pool in patients on antiretroviral therapy.
While several individual studies addressing research productivity of post-graduate students are available, a synthesis of effective strategies to increase productivity and the determinants of ...productivity in low-income countries has not been undertaken. Further, whether or not this research from post-graduate students' projects was applied in evidence-informed decision-making was unknown. Therefore, we conducted a systematic review of literature to identify and assess the effectiveness of approaches that increase productivity (proportion published) or the application (proportion cited) of post-graduate students' research, as well as to assess the determinants of post-graduate students' research productivity and use.
We conducted a systematic review as per our a priori published protocol, also registered in PROSPERO (CRD42016042819). We searched for published articles in PubMed/MEDLINE and the ERIC databases through to July 2017. We performed duplicate assessments for included primary studies and resolved discrepancies by consensus. Thereafter, we completed a structured narrative synthesis and, for a subset of studies, we performed a meta-analysis of the findings using both fixed and random effects approaches. We aligned our results to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
We found 5080 articles in the PubMed (n = 3848) and ERIC (n = 1232) databases. After excluding duplicates (n = 33), we screened 5047 articles, of which 5012 were excluded. We then retrieved 44 full texts and synthesised 14, of which 4 had a high risk of bias. We did not find any studies assessing effectiveness of strategies for increasing publication nor citations of post-graduate research projects. We found an average publication proportion of 7% (95% CI 7-8%, Higgins I-squared 0.0% and Cochran's Q p < 0.01) and 23% (95% CI 17-29%, Higgins I-squared of 98.4% and Cochran's Q, p < 0.01) using fixed effects and random effects models, respectively. Two studies reported on the citation of post-graduate students' studies, at 17% (95% CI 15-19%) in Uganda and a median citation of 1 study in Turkey (IQR 0.6-2.3). Only one included study reported on the determinants of productivity or use of post-graduate students' research, suggesting that younger students were more likely to publish and cohort studies were more likely to be published.
We report on the low productivity of post-graduate students' research in low- and middle-income countries, including the citation of post-graduate students' research in evidence-informed health policy in low- and middle-income countries. Secondly, we did not find a single study that assessed strategies to increase productivity and use of post-graduate students' research in evidence-informed health policy, a subject for future research.
World over, stakeholders are increasingly concerned about making research useful in public policy-making. However, there are hardly any reports linking production of research by students at ...institutions of higher learning to its application in society. We assessed whether and how post-graduate students' research was used in evidence-informed health policies.
This is a multiple case study of master's students' dissertations at Makerere University College of Health Sciences (MakCHS) produced between 1996 and 2010. In a structured review, we applied a theoretical framework of 'research use' and used content analysis to map how research was used in public policy documents. We categorised content of these documents according to the health-related Millennium Development Goals (MDG). We defined a case of 'use' as citation of research products from a master's student's dissertation in a public policy-related document.
We found 22 cases of research use in policy-related documents (0.5%) out of a total 4230 citations from 16 of 1172 total dissertations (1.4%). Additionally, research was mostly cited in primary studies (95.4%), systematic reviews (3%), narrative reviews (0.8%) and cost-effectiveness analyses (0.2%). Research was predominantly used instrumentally, to either frame the problem (burden of disease or health condition) or select an intervention (treatment or diagnostic option) and rarely symbolically to justify strategies already selected. The bulk of the cases of research use addressed child health (MDG 4), focusing on infectious diseases (MDG 6), mainly in international clinical or public health guidelines, working papers, a consensus statement and a global report. We distilled 'synergistic relationships' among organisations or interest groups, 'globalisation of local evidence', 'trade-offs' in the use of research and use of 'negative results' from the documents and text content.
Research from dissertations of post-graduate students at MakCHS is used in evidence-informed health policies, particularly for infectious diseases in child health. Further, we have delineated pathways of research use in the global arena and highlighted the importance of 'negative results' from dissertations of post-graduate students at MakCHS.
HIV Prevention Efforts and Incidence of HIV in Uganda Grabowski, M. Kate; Serwadda, David M; Gray, Ronald H ...
New England journal of medicine/The New England journal of medicine,
11/2017, Letnik:
377, Številka:
22
Journal Article
Recenzirano
Odprti dostop
Preventing HIV infection is a global priority. In this article, the association of the scale-up of male circumcision, HIV treatment, and behavioral interventions on the incidence of HIV infection was ...assessed in Rakai, Uganda.
HICs versus low-income and middle-income countries (LMICs), Global North versus Global South, and resource-rich settings versus resource-poor settings.3 This language conveys a pervasive and harmful ...narrative, powerfully captured by Stephanie Nixon's critique of power systems in her coin model of privilege and critical allyship: the most ethical and effective way to address health disparities is for people on the top of the coin (ie, in positions of privilege) to use their expertise to help marginalised groups with their problems.4 Without countering this narrative, attempts to disrupt inequitable practices in global health are doomed to fail, or worse, reinforce the very hierarchies they seek to uproot. ...participatory action research contributes to epistemic justice by recognising lived experience as a basis of knowing, thus broadening the horizon of what counts as scientific evidence. ...the possibilities offered by participatory methods offer an invigorative perspective on global health practice, and a much-needed opportunity to redefine its scope.12 The narrative of global health needs to be reoriented from saving, helping, and educating vulnerable others, towards working in solidarity and building transformative change.
BACKGROUND: Delayed diagnosis and treatment initiation of smear-negative tuberculosis (TB) patients can lead to increased morbidity and mortality, particularly among those co-infected with the human ...immunodeficiency virus (HIV).OBJECTIVE: To compare TB treatment initiation among
smear-negative presumptive TB patients in the 6 months before and after the introduction of Xpert® MTB/RIF testing at five rural tertiary hospitals in Uganda.METHODS: Patient records of the dates and results of sputum analysis were extracted from TB laboratory registers
and linked to those on treatment initiation as indicated in the TB treatment registers. The proportion of smear-negative presumptive patients who initiated anti-tuberculosis treatment was compared before and after Xpert implementation using χ2 tests. Time to treatment was analysed
using Kaplan-Meier survival analysis.RESULTS: Records from 3658 patients were analysed, 1894 before and 1764 after the introduction of Xpert testing. After the introduction of Xpert, 25% (437/1764) of smear-negative presumptive TB patients underwent testing. The proportion initiated on
anti-tuberculosis treatment increased from 5.9% (112/1894) to 10.8% (190/1764) (P < 0.01). However, 37% (32/87) of patients with a confirmed TB diagnosis did not initiate treatment. Time to TB treatment initiation improved from 8 to 3.5 days between the study periods.CONCLUSION:
Xpert testing was associated with improved TB treatment initiation among smear-negative presumptive TB patients. Improved utilisation and linkage to treatment could improve the impact of this test on patient-centred outcomes.
The experiences and lessons learned by the members of Uganda's National Validation Switch Committee nominated by the Ministry of Health for the removal of type 2 polio vaccine are discussed. The ...experiences and lessons will be used in future immunization processes that will require switching from one vaccine formulation to another such as from measles monovalent to any measles combination vaccine, from tetanus toxoid vaccine to tetanus diphtheria vaccine. These lessons include independence and expertise mix of the National Switch Validation Committee, well-coordinated stakeholders are prime to success, and adapted global guidelines to local context.
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