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Introduction: Young people living with HIV (YPLHIV) are at increased risk of developing chronic kidney disease (CKD) which is associated with high mortality and morbidity. Early diagnosis is important to halt progression. We aimed to estimate the prevalence and factors associated with CKD among YPLHIV in Kampala, Uganda, and to compare serum creatinine and cystatin C for early diagnosis of CKD in this population. Methods: A cross-sectional study with YPLHIV aged 10 to 24 years was conducted in seven HIV clinics. Participants provided a urine and blood sample to measure urinary albumin, proteinuria, serum creatinine and cystatin C levels at baseline and after three months. The estimated glomerular filtration rate (eGFR) was calculated using CKDEPI 2021, Cockroft-Gault and bedside Schwartz equations using creatinine or cystatin C. The albumin creatinine ratio (ACR) and proteinuria were measured. CKD was defined as either eGFR < 60 ml/min/1.73m2 or < 90 ml/min/1.73m2 or ACR above 30 mg/g on two separate occasions. Univariable and multivariable logistic regression were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with CKD. Results: A total of 500 participants were enrolled. Most were female (56%; n = 280) and aged 10 to 17 years (66.9%; n = 335). CKD prevalence ranged from 0 to 23% depending on the criteria, equation and biomarker used. Cystatin C-based equations estimated higher prevalence of CKD compared to creatinine-based ones. Prevalence of ACR above 30 mg/g was 10.1% and of proteinuria 29%. Factors independently associated with CKD were age (aOR = 1.42; 95% CI:1.30–1.51) and male sex (aOR = 3.02; 95% CI:1.68–5.43). Conclusion: CKD prevalence among YPLHIV varied substantially depending on definitions used and the current definition would likely lead to missed cases of CKD among YPLHIV. Estimating equations should be validated against measured GFR in YPLHIV and the optimal definition of CKD in this vulnerable population should be revised to optimise detection and opportunities for reducing disease progression. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Uganda's efforts to end the HIV epidemic by 2030 are threatened by the increasing number of PLHIV with low-level viraemia (LLV). We conducted a study to determine the prevalence of LLV and the association between LLV and subsequent viral non-suppression from 2016 to 2020 among PLHIV on ART in Uganda. Method: This was a retrospective cohort study, using the national viral load (VL) program data from 2016 to 2020. LLV was defined as a VL result of at least 50 copies/ml, but less than 1,000 copies/ml. Multivariable logistic regression was used to determine the factors associated with LLV, and cox proportional hazards regression model was used to determine the association between LLV and viral non-suppression. Results: A cohort of 17,783 PLHIV, of which 1,466 PLHIV (8.2%) had LLV and 16,317 (91.8%) had a non-detectable VL was retrospectively followed from 2016 to 2020. There were increasing numbers of PLHIV with LLV from 2.0% in 2016 to 8.6% in 2020; and LLV was associated with male sex, second line ART regimen and being of lower age. 32.5% of the PLHIV with LLV (476 out of 1,466 PLHIV) became non-suppressed, as compared to 7.7% of the PLHIV (1,254 out of 16,317 PLHIV) with a non-detectable viral load who became non-suppressed during the follow-up period. PLHIV with LLV had 4.1 times the hazard rate of developing viral non-suppression, as compared to PLHIV with a non-detectable VL (adjusted hazard ratio was 4.1, 95% CI: 3.7 to 4.7, p < 0.001). Conclusion: Our study indicated that PLHIV with LLV increased from 2.0% in 2016 to 8.6% in 2020, and PLHIV with LLV had 4.1 times the hazard rate of developing viral non-suppression, as compared to PLHIV with a non-detectable VL. Hence the need to review the VL testing algorithm and also manage LLV in Uganda. [ABSTRACT FROM AUTHOR]

Attaining viral load (VL) suppression for over 95% of the people living with HIV on antiretroviral therapy is a fundamental step in enabling Uganda and other sub-Saharan African countries to achieve global Sustainable Development Goal targets to end the HIV/AIDS epidemic by 2030. In line with the 2013 World Health Organization recommendations, several sub-Saharan African countries, including Uganda, use a threshold of 1000 HIV viral RNA copies/mL to determine HIV viral non-suppression. The United States Centers for Disease Control and Prevention and the International Association of Providers of AIDS Care deem this threshold very high, and hence recommend using 200 copies/mL to determine viral non-suppression. Using 1000 copies/mL as a threshold ignores people living with HIV who have low-level viraemia (LLV; HIV VL of at least 50 copies/mL but less than 1000 copies/mL). Despite the 2021 World Health Organization recommendations of using intensive adherence counselling for people living with HIV with LLV, several sub-Saharan African countries have no interventions to address LLV. However, recent studies have associated LLV with increased risks of HIV drug resistance, virologic failure and transmission. The purpose of this narrative review is to provide insights on the emerging concern of LLV among people living with HIV receiving antiretroviral therapy in sub-Saharan Africa. The review also provides guidance for Uganda and other sub-Saharan African countries to implement immediate appropriate interventions like intensive adherence counselling, reducing VL thresholds for non-suppression and conducting more research to manage LLV which threatens progress towards ending HIV by 2030. [ABSTRACT FROM AUTHOR]

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) 1β, 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-1β (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Disclosure of parental HIV status is associated with a number of positive outcomes such as improved adherence to clinic appointments, lower levels of parental anxiety and depression, and mutual emotional support between parents and their children. Very few studies in low-resource settings have addressed the issues of parental disclosure of their HIV status to their children.Methods: A cross-sectional study was conducted among adult parents attending HIV/AIDS prevention, care and treatment clinic at Makerere University Infectious Diseases Institute (IDI), Kampala, Uganda. Participants were interviewed using the Parent Disclosure Interview (PDI) questionnaire which is a standard tool developed specifically for HIV infected parents. Data were analyzed using STATA version 13.1.Results: Of 344 participants, only 37 % had told at least one of their children that they were HIV positive. Barriers to disclosure were fear that children may tell other people about the parent's HIV status, desire not to worry or upset children and perceptions that children may not understand. Age of the parent, religion and having someone committed to care of the children were positively associated with parental disclosure of their HIV positives status. Attainment of tertiary level of education was negatively associated with parental disclosure of their HIV status.Conclusions: Parental disclosure of a positive HIVstatus to their children is still low in urban Kampala. There is therefore need to develop locally relevant interventions so as to increase rates of parental disclosure of a positive HIV status to their children and thus promote open and honest discussions about HIV/AIDS at family level. [ABSTRACT FROM AUTHOR]

Background: Sputum smear microscopy for tuberculosis (TB) diagnosis lacks sensitivity in HIV-infected symptomatic patients and increases the likelihood that mycobacterial infections particularly disseminated TB will be missed; delays in diagnosis can be fatal. Given the duration for MTB growth in blood culture, clinical predictors of MTB bacteremia may improve early diagnosis of mycobacteremia. We describe the predictors and mortality outcome of mycobacteremia among HIV-infected sputum smear-negative presumptive TB patients in a high prevalence HIV/TB setting. Methods: Between January and November 2011, all consenting HIV-infected adults suspected to have TB (presumptive TB) were consecutively enrolled. Diagnostic assessment included sputum smear microscopy, urine Determine TB lipoarabinomannan (LAM) antigen test, mycobacterial sputum and blood cultures, chest X-ray, and CD4 cell counts in addition to clinical and socio-demographic data. Patients were followed for 12 months post-enrolment. Results: Of 394 sputum smear-negative participants [female, 63.7%; median age (IQR) 32 (28-39) years], 41/394 (10.4%) had positive mycobacterial blood cultures (mycobacteremia); all isolates were M. tuberculosis (MTB). The median CD4 cell count was significantly lower among patients with mycobacteremia when compared with those without (CD4 31 versus 122 cells/μL, p < 0.001). In a multivariate analysis, male gender [OR 3.4, 95%CI (1.4-7.6), p = 0.005], CD4 count <100 cells/μL [OR 3.1, 95% CI (1.1-8.6), p = 0.030] and a positive lateral flow urine TB LAM antigen test [OR 15.3, 95%CI (5.7-41.1), p < 0.001] were significantly associated with mycobacteremia. At 12 months of follow-up, a trend towards increased mortality was observed in patients that were MTB blood culture positive (35.3%) compared with those that were MTB blood culture negative (23.3%) (p = 0.065). Conclusions: Mycobacteremia occurred in 10% of smear-negative patients and was associated with higher mortality compared with smear-negative patients without mycobacteremia. Advanced HIV disease (CD4 < 100 cells/mm³), male gender and positive lateral flow urine TB LAM test predicted mycobacteremia in HIV-infected smear-negative presumptive TB patients in this high prevalence TB/HIV setting. [ABSTRACT FROM AUTHOR]

Background Cataracts contribute 12% of visual loss among HIV-infected adults in Uganda. Immuno-pathogenesis of cataracts may differ among HIV-infected individuals; thus the need for innovative therapeutic interventions among HIV-infected adults. Methods In a laboratory based case-control study, nested in a clinical/surgical community outreach camp, 50 adults with cataracts eligible for surgery were selected consecutively. HIV testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear Cells (PBMC) were collected from all HIV-positive-adults-with-cataracts (cases) and HIV-negative-adults-with-cataracts (comparative group) and age-matched HIV-negative and HIV-positive-adults-without-cataracts (comparative group). Treg were measured as CD3 + CD4 + FoxP3 + CD25+Bright and immune activation as CD3 + CD4 + CD38 + HALDR+ using a Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four groups. Results Of 50 adults operated for cataracts, 24 (48%) were female, 25 (50%) were HIV-positive. HIV-positive-individuals had cataracts earlier [median; Inter-quartile Range (IQR); 49 (44-53) years] than HIV-negative [70 (IQR 59-75) years]; p = 0.0005. Treg were lower among individuals with cataracts irrespective of HIV status; p = 0.001; but comparable among younger HIV-positive and elderly HIV-negative with cataracts; p = 0.301. Immune activation levels were comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive-individuals with cataracts expressed higher levels of immune activation than HIV-positive-individuals without cataracts; p = 0.012 and HIV-negative-individuals-with-cataracts expressed higher levels of immune activation that HIV-negative-without-cataracts; p < 0.0001. Conclusion CD4 T-cell activation and reduced regulatory T-cell populations were associated with cataracts among adults aging with HIV. We recommend studies on clinical relevance of immune modulation in the prevention of early development of cataracts among adults aging with HIV in Africa. [ABSTRACT FROM AUTHOR]

Background: The increased immune activation and inflammation of chronic HIV-infection and the characteristic dyslipidemias associated with HIV infection and antiretroviral therapy (ART) contribute to an increased risk of atherosclerotic vascular disease among HIV-infected adults. There is an emerging need to understand determinants of cardiovascular disease (CVD) among individuals aging with HIV in sub-Saharan Africa. We determined the prevalence of subclinical atherosclerosis [carotid intima media thickness (CIMT) ≥0.78 mm] and its correlation with traditional CVD risk factors among HIV-infected adults. Methods: In a cross-sectional study, HIV-infected adults (ART-naïve and ART-treated) were consecutively selected from patients' enrollment registers at two large HIV clinics at Mulago Hospital, Kampala, Uganda. We measured traditional CVD risk factors including age, biophysical profile, fasting blood sugar and serum lipid profile as well as biomarkers of inflammation. High resolution ultrasound was used to measure common carotid CIMT. Results: Of 245 patients, Median age [Interquartile range (IQR)] 37 years (31–43), 168 (69%) were females; and 100 (41%) were ART-treated for at least 7 years. Overall, 34/186 (18%) had subclinical atherosclerosis; of whom 15/108 (14%) were ART-naïve whereas 19/78 (24%) were ART-treated. Independent predictors of subclinical atherosclerosis included age [odds ratio (OR) 1.83 per 5-year increase in age; 95% confidence interval (CI) 1.24–2.69; p = 0.002], body mass index (BMI); OR 1.15; CI 1.01–1.31; p = 0.041 and high low density lipoprotein (LDL) [OR 2.99; CI 1.02–8.78, p = 0.046]. High sensitivity C-reactive protein (hsCRP) was positively correlated with traditional cardio-metabolic risk factors including waist circumference (r = 0.127, p = 0.05), triglycerides (r = 0.19, p = 0.003) and Total Cholesterol: High Density Lipoprotein ratio (TC:LDL) (r = 0.225, p<0.001). Conclusion: The prevalence of subclinical atherosclerosis was 18% among HIV-infected adults in Uganda. Traditional CVD risk factors were associated with subclinical atherosclerosis. We recommend routine assessment of traditional CVD risk factors within HIV care and treatment programs in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background Up to 40% of HIV-infected individuals receiving Highly Active Antiretroviral Therapy (HAART) have poor CD4+ T-cell recovery. The role of natural killer (NK) cells in immune recovery during HAART is not well understood. We described the profiles of NK cell subsets and their expression of activating receptor, NKG2D and cytotoxicity receptor NKp46 among suboptimal immune responders to despite four years of suppressive HAART. Methods A case control study utilized frozen peripheral blood mononuclear cells (PBMC) from a cohort of HIV-infected adults that initiated HAART in 2004/5, at CD4 < 200 cells/μl. Cases were 'suboptimal' responders; patients within the lowest quartile of CD4+ T-cell reconstitution, with a median CD4 count increase of 129 (-43-199) cells/μl (between baseline and after 4 years of HAART) and controls were 'super-optimal' responders; patients within the highest quartile of CD4 T-cell reconstitution with a median CD4 count increase of 528 (416-878) cells/μl). Expression of NK cell lineage markers (CD56+/-CD16+/-) and receptors NKG2D and NKp46, was measured among PBMC from 29 cases of 'suboptimal' responders' and 23 controls of 'super-optimal responders', and compared among 'suboptimal' and 'superoptimal' responders. NK cell populations were compared using the Holm Sidak multiple comparison test and p values < 0.05 were considered statistically significant. Data was analyzed using FLOWJO and GraphPad Prism 6. Results 'Suboptimal responders' had a higher proportion of cytokine producing CD56++CD16+/- (CD56bri) NK cells than the 'super-optimal responders' p = 0.017, and CD56neg NK cells were lower among suboptimal than super-optimal responders (p = 0.007). The largest NK cell subset, CD56dim, was comparable among suboptimal responders and 'super-optimal immune responders'. Expression of NKG2D and NKp46 receptors on NK cell subsets (CD56bri, CD56neg and CD56dim), was comparable among 'suboptimal' and 'super-optimal' immune responders. Conclusions The pro-inflammatory CD56++CD16-- NK cells were higher among 'suboptimal' responders relative to 'super-optimal' responders, despite four years of suppressive HAART. Alteration of NK cell populations could inhibit host immune responses to infections among suboptimal responders. We recommend further analysis of NK cell function among suboptimal immune responders in order to inform targeted interventions to optimize immune recovery among HAART-treated adults. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. Methods: T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30]. Results: Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022]. Conclusion: T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART. [ABSTRACT FROM AUTHOR]

HIV testing is an entry point to comprehensive HIV/AIDS prevention and care. In Uganda, Routine Testing and Counseling for HIV (RTC) is not widely offered as part of standard medical care in acute care settings. This study determined the acceptance of RTC in a medical emergency setting at Mulago national referral hospital. We interviewed 233 adult patients who were offered HIV testing. Overall, 83% were unaware of their HIV serostatus and 88% of these had been to a health unit in the previous six months. Of the 208 eligible for HIV testing, 95% accepted to test. Half the patients were HIV infected and 77% of these were diagnosed during the study. HIV testing was highly acceptable and detected a significant number of undiagnosed HIV infections. We recommend adoption of RTC as standard of care in the medical emergency unit in order to scale HIV diagnosis and linkage to HIV/AIDS care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]