Effectiveness of intensive adherence counselling in achieving an undetectable viral load among people on antiretroviral therapy with low-level viraemia in Uganda.

INTRODUCTION: Uganda was using a threshold of 1000 copies/mL to determine viral non-suppression for antiretroviral therapy monitoring among people living with HIV, prior to this study. It was not clear whether people living with HIV with low-level viraemia (LLV, ≥50 to <1000 copies/mL) would benefit from intensive adherence counselling (IAC). The purpose of this study was to determine the effectiveness of IAC among people living with HIV, receiving antiretroviral therapy, and with LLV in Uganda, to guide key policy decisions in HIV care, including the review of the viral load (VL) testing algorithm. METHODS: This cluster-randomized clinical trial comprised adults from eight HIV clinics who were living with HIV, receiving ART, and had recent VL results indicating LLV (tested from July 2022 to October 2022). Participants in the intervention arm clinics received three once-monthly sessions of IAC, and those in the comparison non-intervention arm clinics received the standard of care. At the end of the study, all participants were re-tested for VL to determine the proportions of those who then had an undetectable VL (<50 copies/mL). We assessed the statistical association between cross-tabulated variables using Fisher's exact test and then modified Poisson regression. RESULTS: A total of 136 participants were enrolled into the study at eight HIV clinics. All 68 participants in the intervention arm completed all IAC sessions. Only one participant in the non-intervention arm was lost to follow-up. The average follow-up time was 3.7 months (standard deviation [SD] 0.2) and 3.5 months (SD 0.1) in the intervention and non-intervention arms, respectively. In total, 59 (43.7%) of 135 people living with HIV achieved an undetectable VL during the study follow-up period. The effect of IAC on attaining an undetectable VL among people with LLV was nearly twice as high in the intervention arm (57.4%) than in the non-intervention arm (29.9%): adjusted risk ratio 1.9 (95% confidence interval 1.0-3.5), p = 0.037. CONCLUSION: IAC doubled the likelihood of an undetectable VL among people living with HIV with LLV. Therefore, IAC has been instituted as an intervention to manage people living with HIV with LLV in Uganda, and this should also be adopted in other Sub-Saharan African countries with similar settings. GOV IDENTIFIER: NCT05514418.

The clinical utility of cystatin C based eGFR in assessing renal function among HIV/AIDs patients on ART at Mildmay Uganda.

BACKGROUND: In clinical practice, Measurement of estimated glomerular filtration rates (eGFR) is the gold standard assessing renal function the glomerular filtration rate often estimated from plasma creatinine. Several studies have shown Cystatin C based eGFR (Cys C) to be a better parameter for the diagnosis of impaired renal function. Cystatin C based eGFR has been proposed as a potential renal function marker but its use in HIV&AIDS patients has not been well evaluated. METHODS: A cross sectional study was carried out on 914 HIV&AIDS patients on antiretroviral therapy (ART) attending Mildmay Uganda for care and treatment between January to March 2015. Serum Cystatin C based eGFR was measured using the particle enhanced immunoturbidimetric assay. Creatinine was analyzed using enzymatic Creatinine PAP method and creatinine clearance was calculated according to C&G. RESULTS: The sensitivity of Cystatin C based eGFR was 15.1% (95% CI = 8.4, 24) with specificity 99.3% (95% CI = 98- 99.7). The positive and negative predictive values were 70.0% (95% CI 45.7-88.1) and 91.2% (95% CI 98.11-92.94) respectively. The positive likelihood ratio was 18.81 and negative likelihood ratio was 0.85. Cystatin C based eGFR had diagnostic accuracy of 90.7 and area under curve was 0.768. CONCLUSION: Cystatin C based eGFR exhibited a high specificity and a high positive likelihood ratio in diagnosis of kidney disease among HIV&AIDS patients. Cystatin C based eGFR can be used as a confirmatory test.

How to improve research capacity strengthening efforts: learning from the monitoring and evaluation of four research consortia in Africa.

Recent efforts to shift the control and leadership of health research on African issues to Africa have led to increased investments for scientific research capacity strengthening (RCS) on the continent and a greater demand for accountability, value for money and demonstration of return on investment. There is limited literature on monitoring and evaluation (M&E) of RCS systems and there is a clear need to further explore whether the M&E frameworks and approaches that are currently used are fit for purpose. The M&E approaches taken by four African RCS consortia funded under the Developing Excellence in Leadership, Training and Science in Africa (DELTAS) I initiative were assessed using several methods, including a framework comparison of the M&E approaches, semi-structured interviews and facilitated discussion sessions. The findings revealed a wide range in the number of indicators used in the M&E plans of individual consortium, which were uniformly quantitative and at the output and outcome levels. Consortia revealed that additional information could have been captured to better evaluate the success of activities and measure the ripple effects of their efforts. While it is beneficial for RCS consortia to develop and implement their own M&E plans, this could be strengthened by routine engagement with funders/programme managers to further align efforts. It is also important for M&E plans to consider qualitative data capture for assessment of RCS efforts. Efforts could be further enhanced by supporting platforms for cross-consortia sharing, particularly when trying to assess more complex effects. Consortia should make sure that processes for developmental evaluation, and capturing and using the associated learning, are in place. Sharing the learning associated with M&E of RCS efforts is vital to improve future efforts. Investing and improving this aspect of RCS will help ensure tracking of progress and impact of future efforts, and ensure accountability and the return on investment. The findings are also likely applicable well beyond health research.

Human Immunodeficiency Virus Is Associated With Higher Levels of Systemic Inflammation Among Kenyan Adults Despite Viral Suppression.

BACKGROUND: Systemic inflammation independently predicts future cardiovascular events and is associated with a 2-fold increase in cardiovascular disease (CVD) risk among persons living with human immunodeficiency virus (PLHIV). We examined the association between inflammatory markers, HIV status, and traditional CVD risk factors. METHODS: We conducted a cross-sectional study of Kenyan adults with and without HIV seeking care at Kisumu County Hospital. Using a multiplex immunoassay, we measured interleukin (IL) 1ß, IL-6, tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hsCRP) concentrations. We compared inflammatory marker concentrations by HIV status using the Wilcoxon rank-sum test. Multivariable linear regression was used to evaluate associations between inflammatory biomarkers and HIV status, adjusting for CVD risk factors. RESULTS: We enrolled 286 PLHIV and 277 HIV-negative participants. Median duration of antiretroviral therapy for PLHIV was 8 years (interquartile range, 4-10) and 96% were virally suppressed. PLHIV had a 51% higher mean IL-6 concentration (P < .001), 39% higher mean IL-1ß (P = .005), 40% higher mean TNF-α (P < .001), and 27% higher mean hsCRP (P = .008) compared with HIV-negative participants, independent of CVD risk factors. Male sex, older age, and obesity were associated with higher concentrations of inflammatory markers. Restricting to PLHIV, viral load of ≥1000 copies/mL was associated with higher TNF-α levels (P = .013). CONCLUSIONS: We found higher levels of systemic inflammatory biomarkers among PLHIV who were virally suppressed, and this was independent of traditional CVD risk factors. Further longitudinal analyses to determine whether these inflammatory markers predict future CVD events, and are possible therapeutic targets among PLHIV, are warranted.

Innate lymphoid cell dysfunction during long-term suppressive antiretroviral therapy in an African cohort.

BACKGROUND: Innate lymphoid cells (ILC) are lymphoid lineage innate immune cells that do not mount antigen-specific responses due to their lack of B and T-cell receptors. ILCs are predominantly found at mucosal surfaces, as gatekeepers against invading infectious agents through rapid secretion of immune regulatory cytokines. HIV associated destruction of mucosal lymphoid tissue depletes ILCs, among other immune dysfunctions. Studies have described limited restoration of ILCs during the first three years of combined antiretroviral therapy (cART). Little is known about restoration of ILCs during long-term cART, particularly in sub-Saharan Africa which hosts increasing numbers of adults with at least a decade of cART. RESULTS: We examined phenotypes and function of ILCs from peripheral blood mononuclear cells after 12 years of suppressive cART. We report that ILC1 frequencies (T-BET + CD127 + and CD161 +) were higher in cART-treated HIV-infected relative to age-matched health HIV-negative adults; P = 0.04 whereas ILC precursors (ILCP) were comparable in the two groups (P = 0.56). Interferon gamma (IFN-γ) secretion by ILC1 was higher among cART-treated HIV-infected relative to HIV-negative adults (P = 0.03). CONCLUSION: HIV associated alteration of ILC persisted during cART and may likely affect the quality of host innate and adaptive immune responses during long-term cART.

Translational research in Uganda: linking basic science to bedside medicine in a resource limited setting.

BACKGROUND: Translational research is a process of applying knowledge from basic biology and clinical trials to techniques and tools that address critical medical needs. Translational research is less explored in the Ugandan health system, yet, it is fundamental in enhancing human health and well-being. With the current high disease burden in Uganda, there are many opportunities for exploring, developing and utilising translational research. MAIN BODY: In this article, we described the current state, barriers and opportunities for translational research in Uganda. We noted that translational research is underutilised and hindered by limited funding, collaborations, laboratory infrastructure, trained personnel, equipment and research diversity. However, with active collaborations and funding, it is possible to set up and develop thriving translational research in Uganda. Researchers need to leverage existing international collaborations to enhance translational research capacity development. CONCLUSION: Expanding the integration of clinical and translational research in Uganda health care system will improve clinical care.

COVID-19 may exacerbate the clinical, structural and psychological barriers to retention in care among women living with HIV in rural and peri-urban settings in Uganda.

BACKGROUND: Retention of pregnant and breastfeeding women and their infants in HIV care still remains low in Uganda. Recent literature has shown that the effects of COVID-19 mitigation measures may increase disease burden of common illnesses including HIV, Tuberculosis, Malaria and other key public health outcomes such as maternal mortality. A research program was undertaken to locate disengaged HIV positive women on option B+ and supported them to reengage in care. A 1 year follow up done following the tracing revealed that some women still disengaged from care. We aimed to establish the barriers to and facilitators for reengagement in care among previously traced women on option B+, and how these could have been impacted by the COVID-19 pandemic. METHODS: This was a cross sectional qualitative study using individual interviews conducted in June and July, 2020, a period when the COVID-19 response measures such as lockdown and restrictions on transport were being observed in Uganda. Study participants were drawn from nine peri-urban and rural public healthcare facilities. Purposive sampling was used to select women still engaged in and those who disengaged from care approximately after 1 year since they were last contacted. Seventeen participants were included. Data was analysed using the content analysis approach. RESULTS: Women reported various barriers that affected their reengagement and retention in care during the COVID-19 pandemic. These included structural barriers such as transport difficulties and financial constraints; clinical barriers which included unsupportive healthcare workers, short supply of drugs, clinic delays, lack of privacy and medicine side effects; and psychosocial barriers such as perceived or experienced stigma and non-disclosure of HIV sero-status. Supportive structures such as family, community-based medicine distribution models, and a friendly healthcare environment were key facilitators to retention in care among this group. The COVID-19 pandemic was reported to exacerbate the barriers to retention in care. CONCLUSIONS: COVID-19 may exacerbate barriers to retention in HIV care among those who have experienced previous disengagement. We recommend community-based models such as drop out centres, peer facilitated distribution and community outreaches as alternative measures for access to ART during the COVID-19 pandemic.

Chest X-ray interpretation does not complement Xpert MTB/RIF in diagnosis of smear-negative pulmonary tuberculosis among TB-HIV co-infected adults in a resource-limited setting.

BACKGROUND: Chest X-ray (CXR) interpretation remains a central component of the current World Health Organization recommendations as an adjuvant test in diagnosis of smear-negative tuberculosis (TB). With its low specificity, high maintenance and operational costs, utility of CXR in diagnosis of smear-negative TB in high HIV/TB burden settings in the Xpert MTB/RIF era remains unpredictable. We evaluated accuracy and additive value of CXR to Xpert MTB/RIF in the diagnosis of TB among HIV-positive smear-negative presumptive TB patients. METHODS: HIV co-infected presumptive TB patients were recruited from the Infectious Diseases Institute outpatient clinic and in-patient medical wards of Mulago Hospital, Uganda. CXR films were reviewed by two independent radiologists using a standardized evaluation form. CXR interpretation with regard to TB was either positive (consistent with TB) or negative (normal or unlikely TB). Sensitivity, specificity and predictive values of CXR and CXR combined with Xpert MTB/RIF for diagnosis of smear-negative TB in HIV-positive patients were calculated using sputum and/or blood mycobacterial culture as reference standard. RESULTS: Three hundred sixty-six HIV co-infected smear-negative participants (female, 63.4%; hospitalized, 68.3%) had technically interpretable CXR. Median (IQR) age was 32 (28-39) years and CD4 count 112 (23-308) cells/mm3. Overall, 22% (81/366) were positive for Mycobacterium tuberculosis (Mtb) on culture; 187/366 (51.1%) had CXR interpreted as consistent with TB, of which 55 (29.4%) had culture-confirmed TB. Sensitivity and specificity of CXR interpretation in diagnosis of culture-positive TB were 67.9% (95%CI 56.6-77.8) and 53.7% (95%CI 47.7-59.6) respectively, while Xpert MTB/RIF sensitivity and specificity were 65.4% (95%CI 54.0-75.7) and 95.8% (95%CI 92.8-97.8) respectively. Addition of CXR to Xpert MTB/RIF had overall sensitivity and specificity of 87.7% (95%CI 78.5-93.9) and 51.6% (95%CI 45.6-57.5) respectively; 86.2% (95%CI 75.3-93.5) and 48.1% (95%CI 40.7-55.6) among inpatients and 93.8% (95%CI 69.8-99.8) and 58.0% (95%CI 47.7-67.8) among outpatients respectively. CONCLUSION: In this high prevalence TB/HIV setting, CXR interpretation added sensitivity to Xpert MTB/RIF test at the expense of specificity in the diagnosis of culture-positive TB in HIV-positive individuals presenting with TB symptoms and negative smear. CXR interpretation may not add diagnostic value in settings where Xpert MTB/RIF is available as a TB diagnostic tool.

Prevalence and predictors of ocular complications among children undergoing nephrotic syndrome treatment in a resource-limited setting.

BACKGROUND: Nephrotic syndrome is the most common glomerulopathy among children aged 2-18 years and high dose corticosteroids are the backbone of its management. Potentially blinding ocular complications often result from nephrotic syndrome and/or its treatment. We conducted a study to determine the prevalence and predictors of ocular complications among children undergoing nephrotic syndrome treatment at Mulago National Referral Hospital. METHODS: This was a cross-sectional study conducted for three [3] months at the pediatric renal unit of Mulago National Referral Hospital (MNRH). Data from a consecutive sample of 100 children was collected using a semi-structured questionnaire, entered into Epi-data 4.4.2 and exported to STATA 14 for analysis at univariate, bivariate and multivariate levels. A robust Poisson regression model was used to identify predictors of ocular complications. RESULTS: Out of 100 patients examined, 80(80%) had ocular complications. The median age was 10 (IQR: 7-12) and 52 (52%) were girls. The most frequent complications were hypertrichosis and refractive errors in 71% (95%CI 61.1-79.6) and 56% (95%CI 45.7-65.9) of the patients respectively. Age above 10 years was the predictor for ocular complications with a RR = 1.37 (95%CI:1.14-1.64) p = 0.001. CONCLUSIONS: We found a high prevalence of ocular complications among children with nephrotic syndrome in this tertiary hospital. The predictor of ocular complications was age greater than 10 years. We recommend that all children with nephrotic syndrome undergo a baseline ocular examination prior to commencement of treatment and be reviewed periodically by an ophthalmologist.

Monocyte Dysfunction, Activation, and Inflammation After Long-Term Antiretroviral Therapy in an African Cohort.

BACKGROUND: Monocyte dysfunction may persist during antiretroviral therapy (ART). METHODS: Frozen peripheral blood mononuclear cells of 30 human immunodeficiency virus (HIV)-infected ART-treated adults with sustained viral suppression and CD4 counts ≥500 cells/µL were consecutively analyzed for monocyte phenotypes and function. RESULTS: Nonclassical monocytes (CD14+, CD16++), interleukin (IL)-1ß production, and expression of CD40 and CD86 were lower among ART-treated HIV-infected adults relative to age-matched HIV-negative adults (P = .01, P = .01, and P = .02, respectively). Intestinal fatty acid-binding protein, IL6, and soluble CD14 were higher among HIV-infected adults relative to HIV-negative adults (P = .0002, P = .04, and P = .0017, respectively). CONCLUSIONS: Further investigation is required to understand drivers of persistent monocyte activation and dysfunction.

Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort.

BACKGROUND: We examined NK cell phenotypes and functions after seven years of ART and undetectable viral loads (<50 copies/ml) with restored CD4 T-cell counts (≥500 cells/µl) and age-matched healthy-HIV-uninfected individuals from the same community. METHODS: Using flow-cytometry, NK cell phenotypes were described using lineage markers (CD56+/-CD16+/-). NK cell activation was determined by expression of activation receptors (NKG2D, NKp44 and NKp46) and activation marker CD69. NK cell function was determined by CD107a, granzyme-b, and IFN-gamma production. RESULTS: CD56 dim and CD56 bright NK cells were lower among ART-treated-HIV-infected than among age-matched-HIV-negative individuals; p = 0.0016 and p = 0.05 respectively. Production of CD107a (P = 0.004) and Granzyme-B (P = 0.005) was lower among ART-treated-HIV-infected relative to the healthy-HIV-uninfected individuals. NKG2D and NKp46 were lower, while CD69 expression was higher among ART-treated-HIV-infected than healthy-HIV-uninfected individuals. CONCLUSION: NK cell activation and dysfunction persisted despite seven years of suppressive ART with "normalization" of peripheral CD4 counts.

Diversity of vaginal microbiota in sub-Saharan Africa and its effects on HIV transmission and prevention.

The vaginal microbial community ("microbiota") is a key component of the reproductive health of women, providing protection against urogenital infections. In sub-Saharan Africa, there is a high prevalence of bacterial vaginosis, a condition defined by bacterial overgrowth and a shift away from a Lactobacillus-dominated profile toward increased percentages of strict anaerobic species. Bacterial vaginosis is associated with an increased risk of HIV acquisition and transmission, as well as an increased risk of acquiring other sexually transmitted infections, preterm births, and pelvic inflammatory disease. Vaginal microbiota, rich in taxa of strict anaerobic species, disrupts the mucosal epithelial barrier through secretion of metabolites and enzymes that mediate inflammation. Advancements in next-generation sequencing technologies such as whole-genome sequencing have led to deeper profiling of the vaginal microbiome and further study of its potential role in HIV pathogenesis and treatment. Until recently data on the composition of the vaginal microbiome in sub-Saharan Africa have been limited; however, a number of studies have been published that highlight the critical role of vaginal microbiota in disease and health in African women. This article reviews these recent findings and identifies gaps in knowledge about variations in female genital commensal bacteria that could provide vital information to improve the effectiveness of interventions to prevent HIV and other sexually transmitted infections. In addition, we review the effects of pregnancy, contraception, and sexual practices on vaginal microbiome and the potential of vaginal microbiota on HIV transmission and prevention. A better understanding of the role of vaginal microbiota in host susceptibility to HIV infection and its prevention among African women could inform the development of novel local and systemic interventions to minimize new HIV infections among high-risk women.

Acceptability and Predictors of Uptake of Anti-retroviral Pre-exposure Prophylaxis (PrEP) Among Fishing Communities in Uganda: A Cross-Sectional Discrete Choice Experiment Survey.

We used a discrete choice experiment to assess the acceptability and potential uptake of HIV pre-exposure prophylaxis (PrEP) among 713 HIV-negative members of fishing communities in Uganda. Participants were asked to choose between oral pill, injection, implant, condoms, vaginal ring (women), and men circumcision. Product attributes were HIV prevention effectiveness, sexually transmitted infection (STI) prevention, contraception, waiting time, and secrecy of use. Data were analysed using mixed multinomial logit and latent class models. HIV prevention effectiveness was viewed as the most important attribute. Both genders preferred oral PrEP. Women least preferred the vaginal ring and men the implant. Condom use was predicted to decrease by one third among men, and not to change amongst women. Oral PrEP and other new prevention technologies are acceptable among fishing communities and may have substantial demand. Future work should explore utility of multiple product technologies that combine contraception with HIV and other STI prevention.

Towards a definition of male partner involvement in the prevention of mother-to-child transmission of HIV in Uganda: a pragmatic grounded theory approach.

BACKGROUND: Male partner involvement has been shown to increase mothers' uptake of Prevention of Mother-to-Child Transmission of HIV (PMTCT) and improve maternal and infant HIV treatment outcomes. Currently, male involvement in PMTCT is measured primarily through men's attendance at HIV testing and counselling which may not be a true reflection of their engagement. This study therefore set out to explore the meaning of male partner involvement and propose a definition and theoretical model of this concept in PMTCT in Uganda. METHODS: Eight focus group discussions and five in-depth interviews were conducted with couples at three public health facilities and community members in the health facility catchment areas in Uganda. The study employed a grounded theory approach underpinned by the pragmatic philosophical paradigm. Data were analyzed using the constant comparative method, performing three levels of open, axial, and selective coding. RESULTS: Of the 61 participants, 29 (48%) were male and the majority 39 (63.9%) were in long term marital relationships, while about half were self-employed 29 (47.5%). Three themes emerged for the meaning of male involvement in PMTCT (a) HIV treatment support (b) economic support and (c) psychosocial support. HIV treatment support included adherence support, couples' HIV counseling and testing, and clinic attendance during and after pregnancy. Participants expressed that men were engaged in PMTCT when they offered economic support by providing basic needs and finances or when they included their female partners in financial planning for the family. Psychosocial support arose from the female participants who defined male involvement as family support, perceived societal recognition and emotional support. Emotional support also included the absence of harm resulting from women's disclosure of HIV test results to their male partner. CONCLUSIONS: This study proposes a new definition for male partner involvement in PMTCT in Uganda. The definition extends beyond men's clinic attendance and HIV testing and counselling. Further research should seek to develop and validate tools to accurately measure male partner involvement as the next step in the development of interventions to improve PMTCT outcomes.

Challenges faced by caregivers of virally non-suppressed children on the intensive adherence counselling program in Uganda: a qualitative study.

BACKGROUND: Of the estimated 130,000 children living with HIV in Uganda, 47% are receiving ART. Only 39.3% have suppressed HIV-1 viral load to levels below 50 copies per ml. Caregivers are key drivers of adherence to achieve viral suppression in children. We investigated the challenges and potential support required by caregivers of ART-treated children. METHODS: A qualitative study was conducted within the Infectious Diseases Institute paediatric ART program in Kampala and Hoima districts. Caregivers of children with viral loads above 1000 copies were purposively sampled and engaged in five focus group discussions (FGD). The FGD guide highlighted questions on challenges that caregivers face and the kind of support they required to improve children's ART adherence. Thematic analysis using the inductive approach was used. All the transcripts were read, coded and emergent themes determined. RESULTS: Overall, 37 caregivers participated in five FGD, of whom 29 (78%) were female, 28 (76%) were HIV-infected and 25 (68%) were biological parents of the children. The elicited challenges were either in failure to attend the counselling sessions or in supporting adherence to medication. Individual and health system challenges such as competing priorities, logistics, poor quality of counselling and lack of reminders prevented attendance at counselling sessions. Five themes emerged as challenges to supporting adherence: i) environmental (school activities, working away from home), ii) personal (non-disclosure, stigma), iii) psychological (guilt), iv) financial (lack of food and transport) and v) child-related (fatigue and peer influence). Three major themes emerged for the support that caregivers needed namely: a) health system reforms (clinic appointments outside school hours, minimize ART drug stock outs and improve quality of counselling), b) psychosocial support (support with disclosure of HIV status to children and their families, more frequent peer support groups and parenting classes) and c) economic empowerment (training in vocational skills, school fees support and opportunities to initiate income generating activities). DISCUSSION AND CONCLUSION: To achieve viral suppression, ART programs require targeted efforts to provide specific health facility requirements, psychological and economic needs of ART-treated children and their caregivers. Integration of HIV treatment with programs for orphans and vulnerable children may improve viral suppression rates.

Prevalence and factors associated with dental caries in patients attending an HIV care clinic in Uganda: a cross sectional study.

BACKGROUND: Chronic Human Immunodeficiency Virus (HIV) infection is associated with reduced saliva flow rate due to infiltration of HIV and proliferation of CD8 lymphocytes in salivary glands. It is unclear whether HIV infection and antiretroviral therapy (ART) increase caries risk. This study aimed to determine the prevalence and factors associated with dental caries in HIV infected adults attending the Mulago Immune Suppression Syndrome (ISS) clinic in Uganda. METHODS: A cross-sectional study was conducted among HIV infected persons. Dental examinations were performed by two calibrated dentists using the WHO Radke's caries classification criteria and reported using the decayed (D), missing (M), filled (F), teeth (DMFT) index. The prevalence and factors associated with dental caries was examined through linear regression analyses. RESULTS: Overall, 748 participants (females = 491, 65.6%) with a mean age of 39 ± 9.4 years were included in the final analysis; of whom 83.7% had caries (DMFT> 0), with a significantly (p < 0.05) higher prevalence among females 86.6% than males 78.2%. The mean DMFT was 5.9 ± 5.5, with statistically significant differences based on gender (males 4.9 ± 4.8 and females 6.3 ± 5.9, p < 0.05) and duration on ART (< 2 years 4.8 ± 4.4, > 2 years but < 5 years 5.7 ± 5.5, > 5 years 6.6 ± 6.0 p < 0.05). The majority (67.2%) of participants reported brushing their teeth twice or more a day, and sugar intake was not associated with dental caries. CONCLUSION: Caries prevalence is high among HIV infected adults under care. Duration of ART was associated with increased risk and severity of caries. Therefore, we recommend integration of dental care in HIV treatment programs.

Reaching the First 90 in Uganda: Predictors of Success in Contacting and Testing the Named Sexual Partners of HIV+ Index Clients in Kiboga District.

Assisted partner notification programs represent one strategy for targeted HIV testing and treatment of exposed individuals in high-risk populations. This study of a pilot Partner Services program in rural Uganda describes predictors of successful contact tracings and testing of partners of HIV+ individuals and possible barriers to contact. Partner contact tracing data was extracted from registers at seven Ministry of Health facilities between May and October 2016, to inform program implementation and scale up. A total of 464 HIV+ index clients named 660 sexual partners; 334/660 (51%) were contacted, 193/334 (58%) tested for HIV, and 61/193 (32%) tested HIV+. Current relationship status predicted contact [AOR = 0.23; (95% CI 0.15, 0.37), p < 0.0001] and testing [AOR = 0.19; (95% CI 0.09, 0.36), p < 0.0001]. Partner contact information type was associated with contact (p < 0.0001), and assisted disclosure with testing (p < 0.0001). Partner contact tracing is an effective means of identifying undiagnosed HIV infections.

"Tuberculosis in advanced HIV infection is associated with increased expression of IFNγ and its downstream targets".

BACKGROUND: Tuberculosis (TB) is the major cause of death in Human Immunodeficiency Virus (HIV)-infected individuals. However, diagnosis of TB in HIV remains challenging particularly when HIV infection is advanced. Several gene signatures and serum protein biomarkers have been identified that distinguish active TB from latent infection. Our study was designed to assess if gene expression signatures and cytokine levels would distinguish active TB in advanced HIV. METHODS: We conducted a case-control study of whole blood RNA-Seq and plasma cytokine/chemokine analysis in HIV-infected with CD4+ T cell count of ≤ 100 cells/µl, with and without active TB. Next, the overlap of the differentially expressed genes (DEG) with the published signatures was performed and then receiver operator characteristic (ROC) analysis was done on small gene discriminators to determine their performance in distinguishing TB in advanced HIV. ELISA was performed on plasma to evaluate cytokine and chemokine levels. RESULTS: Hierarchical clustering of the transcriptional profiles showed that, in general, HIV-infected individuals with TB (TB-HIV) clustered separately from those without TB. IPA indicated that the TB-HIV signature was characterized by an increase in inflammatory signaling pathways. Analysis of overlaps between DEG in our data set with published TB signatures revealed that significant overlap was seen with one TB signature and one TB-IRIS signature. ROC analysis revealed that transcript levels of FcGR1A (AUC = 0.85) and BATF2 (AUC = 0.82), previously reported as consistent single gene classifiers of active TB irrespective of HIV status, performed successfully even in advanced HIV. Plasma protein levels of IFNγ, a stimulator of FcGR1A and BATF2, and CXCL10, also up-regulated by IFNγ, accurately classified active TB (AUC = 0.98 and 0.91, respectively) in advanced HIV. Neither of these genes nor proteins distinguished between TB and TB-IRIS. CONCLUSIONS: Gene expression of FcGR1A and BATF2, and plasma protein levels of IFNγ and CXCL10 have the potential to independently detect TB in advanced HIV. However, since other lung diseases were not included in this study, these final candidates need to be validated as specific to TB in the advanced HIV population with TB.

Effects of HIV infection and ART on phenotype and function of circulating monocytes, natural killer, and innate lymphoid cells.

HIV infection causes upregulation of markers of inflammation, immune activation and apoptosis of host adaptive, and innate immune cells particularly monocytes, natural killer (NK) and innate lymphoid cells (ILCs). Although antiretroviral therapy (ART) restores CD4 T-cell counts, the persistent aberrant activation of monocytes, NK and ILCs observed likely contributes to the incomplete recovery of T-cell effector functions. A better understanding of the effects of HIV infection and ART on the phenotype and function of circulating monocytes, NK, and ILCs is required to guide development of novel therapeutic interventions to optimize immune recovery.

Elevated inflammatory cytokines in aqueous cytokine profile in HIV-1 infected patients with cataracts in Uganda.

BACKGROUND: Cataracts occur earlier among HIV-infected adults and this is attributed to various intraocular inflammatory processes that result in early degeneration. In this study we purposed to investigate whether HIV infected individuals with cataracts develop heightened intraocular inflammatory processes compared to their HIV negative counterparts by determining the concentration of 8 cytokines in the aqueous humour of HIV-positive adults with cataracts and their HIV-negative counterparts. METHODS: A cross-sectional study was conducted among consecutive adults with cataracts that were operated in an ophthalmology surgical camp in western Uganda. We determined levels of Granulocyte macrophage stimulating factor (GM-CSF), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrotic factor alpha (TNF-a), interferon gamma (IFN-g), interleukin 4 (IL-4), interleukin 2 (IL-2), and interleukin (IL-10) in the aqueous fluid using a multiplexed cytokine analysis. Data was entered in the SPSS version 10 and analyzed using STATA statistical software version 7.0. Categorical and continuous variables were compared using the χ2 test, Fisher's exact test and the Student's t-test. Bonferroni correction was used to cater for multiple comparison of p values for the various cytokines. RESULTS: The 50 adults that underwent cataract surgery were outdoor peasants with similar exposure hours to UV radiation. The HIV-positive patients were younger {median age 43 years (SD 11.741)} compared to the HIV -negative patients {median age 66.5 years (SD 21.4)}. The mean CD4+ T cell count of the HIV-positive patients was 161 cells /mm3, and 12(48%) had started anti-retroviral therapy (ART). Pro inflammatory cytokines, GM-CSF, IL-8 and IL-10 were significantly higher among HIV-positive individuals (p = 0.001, 0.030, < 0.001 respectively). HIV-positive individuals on ART also showed significantly higher levels of GM-CSF, IL-8 and IL - 10 (p = 0.002, 0.021, < 0.001 respectively). TNF-a and IL-4 were significantly higher among those with a CD4+ T cell count greater than 200cells/mm3 compared to those with CD4+ T cell count less than 200 cells/mm3 (p = 0.022, 0.032 respectively). CONCLUSION: Cataracts among HIV-positive adults were associated with higher intraocular inflammation relative to the healthy elderly individuals with cataracts. There is need to explore the potential role of intra-ocular anti-inflammatory agents in the management of cataracts among HIV positive patients.