Prevalence and viral suppression of hepatitis B virus infection among people living with HIV on antiretroviral therapy in Sierra Leone.

OBJECTIVE: Sub-Saharan Africa is one of the regions with the highest burdens of HIV and hepatitis B virus (HBV), but data on the impact of antiretroviral therapy (ART) on HBV DNA suppression is limited. In this study, we aimed to determine the prevalence and associated factors of a positive hepatitis B surface antigen (HBsAg) among people living with HIV, and assess the suppression of ART on HBV replication in people living with HIV in Sierra Leone. METHODS: A cross-sectional study was designed to recruit people living with HIV aged 18 years or older in ten public hospitals in Sierra Leone between August 2022 and January 2023. Statistical analyses were performed using R software. Logistic regression analysis was used to assess factors independently associated with positive HBsAg and HBV DNA suppression. RESULTS: Of the 3106 people living with HIV recruited in this study, 2311 (74.4%) were women. The median age was 36 years, 166 (5.3%) had serological evidence of HBV vaccination. The overall prevalence of HBsAg positivity was 12.0% (95% CI: 10.9% to 13.2%). Male sex (adjusted OR (aOR) 2.11, 95% CI: 1.67 to 2.68; p<0.001) and being separated (aOR 1.83, 95% CI: 1.06 to 3.16, p=0.031; reference group: being married) were independent predictors of HBsAg seropositivity. Among 331 people living with HIV and HBV receiving ART, 242 (73.1%) achieved HBV DNA suppression (below 20 IU/mL). HBV suppression rate was higher in HIV-virally suppressed patients than those with unsuppressed HIV viral load (p<0.001). In addition, the male sex was more likely to have unsuppressed HBV DNA (aOR 1.17, 95% CI: 1.17 to 3.21; p=0.010). CONCLUSIONS: We reported a high prevalence of HBsAg seropositivity and low HBV immunisation coverage in people living with HIV in Sierra Leone. In addition, we observed that ART can efficiently result in a viral suppression rate of HBV infection. Therefore, achieving the global target of eliminating HBV infection by 2030 requires accelerated access to care for people living with HIV and HBV, including HBV testing, antiviral treatment and hepatitis B vaccination.

Impact of COVID-19 on the Utilization of HIV Testing and Linkage Services in Sierra Leone: Experience from Three Public Health Facilities in Freetown.

The COVID-19 pandemic adversely affected the delivery of essential health services globally. In this study, we aimed to assess the impact of the pandemic on HIV testing and linkage services at three public health facilities in Freetown, Sierra Leone. We conducted a retrospective study to assess the impact of COVID-19 on HIV testing and linkage to treatment services (HTS) at Connaught Hospital (CH-tertiary), Lumley Government Hospital (LGH-secondary) and George Brooke Community Health Center (GBC-primary) in Freetown. Statistical analyses were conducted in Stata (16.1, StataCorp LLC, College Station, TX). Intra-pandemic HTS (2020) and HTS during recovery (2021) were compared with pre-pandemic HTS (2019). Of the 8538 people tested for HIV in the three facilities, 4929 (57.5%) visited CH. Only 2249 people were tested for HIV in 2020 compared to 3825 in 2019 (difference: - 41.2%, P < 0.001). Fewer people were also tested in 2021 (difference: - 35.6% P < 0.001). The largest reductions in testing in 2020 occurred in women (- 47.7%), children under 15 (- 95.2%), married people (- 42.6%), and CH (- 46.2%). Overall, 1369 (16.0%) people were positive for HIV; CH (878, 17.9%), LGH (469, 15.6%) and GBC (22, 3.5%). The likelihood of a positive HIV test was 26% lower in 2020 than 2019 (PR 0.74; 95% CI 0.64-0.85; P < 0.001), but 16% higher in 2021 than 2019 (PR 1.16; 95% CI 1.03-1.30; P < 0.05). Of the 1369 HIV diagnosis, 526 (38.4%) were linked to care. We found significant disruptions in HIV testing and linkage services at different levels of service delivery during the COVID-19 pandemic, underscoring the need to strengthen essential health services during public health emergencies.

Prevalence and determinants of hepatitis delta virus infection among HIV/hepatitis B-coinfected adults in care in the United States.

Hepatitis delta virus (HDV) infection increases the risk of liver complications compared to hepatitis B virus (HBV) alone, particularly among persons with human immunodeficiency virus (HIV). However, no studies have evaluated the prevalence or determinants of HDV infection among people with HIV/HBV in the US. We performed a cross-sectional study among adults with HIV/HBV coinfection receiving care at eight sites within the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) between 1996 and 2019. Among patients with available serum/plasma specimens, we selected the first specimen on or after their initial HBV qualifying test. All samples were tested for HDV IgG antibody and HDV RNA. Multivariable log-binomial generalized linear models were used to estimate prevalence ratios (PRs) with 95% CIs of HDV IgG antibody-positivity associated with determinants of interest (age, injection drug use [IDU], high-risk sexual behaviour). Among 597 adults with HIV/HBV coinfection in CNICS and available serum/plasma samples (median age, 43 years; 89.9% male; 52.8% Black; 42.4% White), 24/597 (4.0%; 95% CI, 2.4%-5.6%) were HDV IgG antibody-positive, and 10/596 (1.7%; 95% CI, 0.6%-2.7%) had detectable HDV RNA. In multivariable analysis, IDU was associated with exposure to HDV infection (adjusted PR = 2.50; 95% CI, 1.09-5.74). In conclusion, among a sample of adults with HIV/HBV coinfection in care in the US, 4.0% were HDV IgG antibody-positive, among whom 41.7% had detectable HDV RNA. History of IDU was associated with exposure to HDV infection. These findings emphasize the importance of HDV testing among persons with HIV/HBV coinfection, especially those with a history of IDU.

Measuring stigma associated with hepatitis B virus infection in Sierra Leone: Validation of an abridged Berger HIV stigma scale.

Stigma associated with hepatitis B virus (HBV) is common in endemic countries; however; instruments are lacking to accurately measure HBV-related stigma. We therefore aimed to develop and validate a concise instrument for measuring perceived HBV-related stigma in Sierra Leone. We enrolled 220 people living with HBV (PWHB) aged ≥18 years from August to November 2022. The initial Likert-scale instrument entailed 12 items adapted from Berger's HIV Stigma Scale. We included four additional items adapted from the USAID indicators for enacted stigma. The proposed scale's psychometric properties were assessed. After item reduction, the final HBV Stigma Scale consisted of 10 items and had good internal consistency (overall Cronbach's α = 0.74), discriminant, and construct validity. Exploratory factor analysis produced a three-dimensional structure accounting for 59.3% of variance: personalized stigma driven by public attitudes (six items), negative self-image (two items), and disclosure concerns (two items). Overall, 72.8% of respondents reported perceived HBV-related stigma (mean score 29.11 ± 4.14) and a similar proportion (73.6%) reported at least one instance of enacted stigma. In assessing criterion-related validity, perceived HBV-related stigma correlated strongly with enacted stigma (r = 0.556) and inversely with having family/friends with HBV (r = -0.059). The 10-item HBV Stigma Scale demonstrated good internal consistency and validity and is suitable for screening for HBV-related stigma in Sierra Leone. The psychometric properties of the scale can be optimized with item additions/modifications and confirmatory factor analysis. The scale may help in combating stigma as a barrier to achieving HBV global elimination goals.

HIV viral suppression at different thresholds and duration of treatment in the dolutegravir treatment era in Sierra Leone: a nationwide survey.

INTRODUCTION: Viral load assessment for people living with HIV is key for monitoring treatment and achieving the 95-95-95. In this study, we aimed to assess the degree of viral suppression at different thresholds and treatment duration after the introduction of dolutegravir-based therapy in ten public hospitals in Sierra Leone. METHODS: We used a cross-sectional study design to recruits patients aged 18 years or older between August 2022 and January 2023. Statistical analyses were performed using R-software. Logistic regression was used to assess factors independently associated with viral suppression. The level of significance was set at P < 0.05. RESULTS: Of the 2,253 patients recruited, 1,720 (76%) were women and 1,705 (76%) were receiving a fixed dose combination of tenofovir, lamivudine and dolutegravir. The median age and duration of anti-retroviral therapy (ART) was 36.0 (IQR, 28.0-45.0) years and 40.9 (IQR, 14.4-79.6) months, respectively. Using a threshold of HIV RNA < 1000 copies/mL, 1,715 (88.4%) patients on ART for more than 6 months were virally suppressed. Viral suppression rates were higher with dolutegravir-based (1,277, 89.5%) than efavirenz-based (418, 86.2%) ART. HIV RNA was < 200 copies/mL in 1,643 (84.6%) patients or < 50 copies/mL in 1,487 (76.6%) patients or between 50 and 999 copies/mL in 228 (11.7%) patients. Viral suppression rates at different ART durations (months) were as follows: 84.2% (≤ 3), 88.8% (4-6), 90.9% (6-12), and 88.1% (> 12). Viral suppression rates were higher for patients aged 40 or older (40-50 years: aOR 2.05, 95%CI 1.41-3.04, P < 0.01; 50-60 years: aOR 2.51, 95%CI 1.53-4.35, P < 0.01; >60 years: aOR 2.69, 95%CI 1.28-6.63, P = 0.02). Men had 49% lower odds of viral suppression than women (aOR 0.50, 95% CI 0.38-0.67, P < 0.01). CONCLUSION: We report a viral suppression rate of 88.4% among patients on treatment for at least 6 months, with higher rate of suppression with dolutegravir than efavirenz. Factors associated with virological suppression were age and gender, emphasizing the need for innovative differentiated ART delivery models to optimize viral suppression and achieve the 95% target.

Should dolutegravir always be withheld in people with HIV on dolutegravir with incident diabetes mellitus? a case report.

Dolutegravir (DTG), an integrase strand transfer inhibitor is currently the recommended first and second line anti-retroviral therapy (ART) anchor agent by the World Health Organization due to its favorable side effect profile, high efficacy and genetic barrier to resistance.Despite its very good side effect profile, there have been multiple case reports of ART experienced patients developing hyperglycemia within weeks to a few months after switching to DTG preceded by weight loss. At population level, however, DTG as well as other integrase inhibitors have been demonstrated to have a reduced risk of incident diabetes mellitus (T2DM) compared to other HIV drug classes.Following multiple similar reports of accelerated hyperglycemia in Uganda during the first pilot year of DTG use, the Uganda Ministry of Health recommended withholding dolutegravir in all patients who develop diabetes. Whether this recommendation should be applied to all patients with incident T2DM remains to be demonstrated.We present a clinical case of an HIV positive ART naïve man who was diagnosed with T2DM after 36 weeks on DTG. We describe changes in blood glucose, glycated hemoglobin, insulin resistance and pancreatic beta cell function before and after withholding DTG. We demonstrated that he was phenotypically different from the reported cases of accelerated hyperglycemia and he continued to have worsening insulin resistance despite withholding DTG. His blood glucose improved with dietary T2DM management. It is possible he had an inherent risk of developing T2DM independent of his exposure to DTG. This put in question whether DTG should universally be withheld in PLHIV with incident T2DM in Uganda.

Sero-prevalence of syphilis infection among people living with HIV in Sierra Leone: a cross-sectional nationwide hospital-based study.

BACKGROUND: Globally, there were an estimated 7.1 million new syphilis infections in 2020, with more than 30% of these new infections reported in African countries such as Sierra Leone. Despite this, there is no HIV-specific syphilis screening program in Sierra Leone. Thus, data are needed to inform public health practice. In this study, we aimed to determine the prevalence of syphilis seropositivity and factors associated with syphilis seropositivity among people living with HIV (PLHIV). METHODS: A cross-sectional study was conducted at 10 health facilities in Sierra Leone, among adults with HIV, aged 18 years or older, from September 2022 to January 2023. Parameters of interest were collected including age, sex, marriage, antiretroviral therapy (ART) regimen, HIV viral load, duration of ART treatment, and hospital level of care. The syphilis antibody was detected by a rapid test based on immunochromatography assay. Data were analyzed using R-software version 4.2.3 (R Core Team, Vienna, Austria). Pearson's χ2 test, Fisher's exact test and Kruskal-Wallis H test were applied to assess the differences in syphilis seropositivity between groups as appropriate. Univariate logistic regression and multivariate logistic regression analysis was used to assess factors associated with syphilis seropositivity. The level of statistical significance was set at P < 0.05. RESULTS: Of the 3082 PLHIV individuals in our study, 2294 (74.4%) were female and 2867 (93.0%) were receiving ART. With a median age of 36 years, 211 (6.8%, 95% CI 6.0-7.7) were positive for syphilis. The prevalence of syphilis was highest in people aged 60 years and over (21.1%, 95%CI 14.7-29.2), followed by people aged 50-60 years (15.5%, 95%CI 11.9-19.9) and in the widowed population (11.9%, 95%CI 8.9-15.8). There were no differences in syphilis seropositivity between gender, ART status, ART regimen, duration of ART, HIV viral load and hospital level of care. Older age (50-60 years: adjusted OR 3.49, 95%CI 2.09-5.85 P < 0.001; 60-100 years: adjusted OR 4.28, 95%CI 2.21-8.17, P < 0.001) was an independent predictor of seropositive syphilis. CONCLUSIONS: We observed a high prevalence of syphilis among PLHIV. Older people and widowed population have higher syphilis seropositivity. Older age was an independent predictor of syphilis positivity. Therefore, we call for the integration of syphilis screening, treatment and prevention in HIV services.

Determinants of incomplete childhood hepatitis B vaccination in Sierra Leone, Liberia, and Guinea: Analysis of national surveys (2018-2020).

Vaccination against hepatitis B virus (HBV) is effective at preventing vertical transmission. Sierra Leone, Liberia, and Guinea are hyperendemic West African countries; yet, childhood vaccination coverage is suboptimal, and the determinants of incomplete vaccination are poorly understood. We analyzed national survey data (2018-2020) of children aged 4-35 months to assess complete HBV vaccination (receiving 3 doses of the pentavalent vaccine) and incomplete vaccination (receiving <3 doses). Statistical analysis was conducted using the complex sample command in SPSS (version 28). Multivariate logistic regression was used to identify determinants of incomplete immunization. Overall, 11,181 mothers were analyzed (4,846 from Sierra Leone, 2,788 from Liberia, and 3,547 from Guinea). Sierra Leone had the highest HBV childhood vaccination coverage (70.3%), followed by Liberia (64.6%) and Guinea (39.3%). Within countries, HBV vaccination coverage varied by socioeconomic characteristics and healthcare access. In multivariate regression analysis, factors that were significantly associated with incomplete vaccination in at least one country included sex of the child, Muslim mothers, lower household wealth index, <4 antenatal visits, home delivery, and distance to health facility vaccination (all p < 0.05). Understanding and addressing modifiable determinants of incomplete vaccination will be essential to help achieve the 2030 viral hepatitis elimination goals.

Antibiotic use and consumption among medical patients of two hospitals in Sierra Leone: a descriptive report.

BACKGROUND: Although one of the main drivers of antimicrobial resistance is inappropriate antibiotic prescribing, there are limited resources to support the surveillance of antibiotic consumption in low-income countries. In this study, we aimed to assess antibiotic use and consumption among medical patients of two hospitals in different geographic regions of Sierra Leone. METHODS: This is a cross-sectional study of adult (18 years or older) patients receiving medical care at two hospitals (34 Military Hospital-MH and Makeni Government Hospital-MGH) between March 2021 and October 2021. After admission to the medical or intensive care unit, patients were sequentially recruited by a nurse from each hospital. Demographic and clinical characteristics and information on the dose of antibiotics, their routes, and frequency of administration and duration were collected using a questionnaire adapted from previous studies and encrypted in EpiCollect software (Epic, Verona WI). A physician reviews and verifies each completed questionnaire. Data analysis was done using STATA version 16. RESULTS: The mean age of the 468 patients evaluated in this study was 48.6 years. The majority were women (241, 51.7%) and treated at MGH (245, 52.0%). Clinical diagnosis of bacterial infection was made in only 180 (38.5%) patients. Regardless of the diagnosis, most (442, 94.9%) patients received at least one antibiotic. Of a total 813 doses of antibiotics prescribed by the two hospitals, 424 (52.2%) were administered in MH. Overall, antibiotic consumption was 66.9 defined daily doses (DDDs) per 100 bed-days, with ceftriaxone being the most commonly used antibiotic (277, 34.1%). The ACCESS and WATCH antibiotics accounted for 18.9 DDDs per 100 bed-days (28.2%) and 48.0 DDDs per 100 bed-days (71.7%), respectively. None of the patients were prescribed a RESERVE antibiotics. The antibiotic consumption was lower in MH (61.3 DDDs per 100 bed-days) than MGH (76.5 DDDs per 100 bed-days). CONCLUSION: Antibiotic consumption was highest with ceftriaxone, followed by levofloxacin and metronidazole. Given the high rate of consumption of antibiotics in the WATCH category of the AWaRe classification, there is a need to initiate surveillance of antibiotic consumption and establish hospital-based antibiotic stewardship in these settings.

Do disempowered childbearing women give birth at home in Sierra Leone? A secondary analysis of the 2019 Sierra Leone demographic health survey.

BACKGROUND: A nationwide assessment of the link between women's empowerment and homebirth has not been fully examined in Sierra Leone. Our study examined the association between women's empowerment and homebirth among childbearing women in Sierra Leone using the 2019 Sierra Leone Demographic Health Survey (2019 SLDHS) data. METHOD: We used the individual file (IR) of the 2019 SLDHS dataset for our analysis. A total of 7377 women aged 15-49 years who gave birth in the five years preceding the survey were included. Outcome variable was "home birth of their last child among women in the five years preceding the 2019 SLDHS. Women's empowerment parameters include women's knowledge level, economic participation, decision-making ability and power to refuse the idea of intimate partner violence. We used the complex sample command on SPSS version 28 to conduct descriptive and multivariate logistic regression analyses. RESULTS: Three in every 20 women had home childbirth (n = 1177; 15.3%). Women with low [aOR 2.04; 95% CI 1.43-2.92] and medium [aOR 1.44; 95%CI 1.05-1.97] levels of knowledge had higher odds of giving birth at home compared to those with high levels of knowledge. Women who did not have power to refuse the idea of intimate partner violence against women were more likely to had given birth at home [aOR 1.38; 95% CI1.09-1.74]. In addition, women with no [aOR 2.71; 95% CI1.34-5.46) and less than four antenatal care visits [aOR 2.08; 95% CI:1.51-2.88] and for whom distance to a health facility was a major problem [aOR 1.95; 95% CI1.49-2.56] were more likely to have had a homebirth. However, no statistically significant association was observed between a women's decision-making power and home birth [aOR 1.11; 95% CI 0.86-1.41]. CONCLUSION: Despite improvements in maternal health indicators, homebirth by unskilled birth attendants is still a public health concern in Sierra Leone. Women with low knowledge levels, who did not have power to refuse the idea of intimate partner violence against women, had less than four ANC visits and considered distance to a health facility as a major problem had higher odds of giving birth at home. Our findings reflect the need to empower women by improving their knowledge level through girl child and adult education, increasing media exposure, changing societal norms and unequal power relations that promote gender-based violence against women, and improving roads and transport infrastructure.

Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir.

BACKGROUND: Following reports of anti-retroviral therapy (ART) experienced Ugandan people living with HIV (PLHIV) presenting with diabetic ketoacidosis weeks to months following a switch to dolutegravir (DTG), the Uganda Ministry of Health recommended withholding DTG in both ART naïve and experienced PLHIV with diabetes mellitus (T2DM), as well as 3-monthly blood glucose monitoring for patients with T2DM risk factors. We sought to determine if the risk of T2DM is indeed heightened in nondiabetic ART naïve Ugandan PLHIV over the first 48 weeks on DTG. METHODS: Between January and October 2021, 243 PLHIV without T2DM were initiated on DTG based ART for 48 weeks. Two-hour oral glucose tolerance tests (2-h OGTT) were performed at baseline, 12, and 36 weeks; fasting blood glucose (FBG) was measured at 24 and 48 weeks. The primary outcome was the incidence of T2DM. Secondary outcomes included: incidence of pre-Diabetes Mellitus (pre-DM), median change in FBG from baseline to week 48 and 2-h blood glucose (2hBG) from baseline to week 36. Linear regression models were used to determine adjusted differences in FBG and 2hBG from baseline to weeks 48 and 36 respectively. RESULTS: The incidence of T2DM was 4 cases per 1000 PY (1/243) and pre-DM, 240 cases per 1000 person years (PY) (54/243). There was a significant increase in FBG from baseline to week 48 [median change from baseline (FBG): 3.6 mg/dl, interquartile range (IQR): - 3.6, 7.2, p-value (p) = 0.005] and significant reduction in 2hBG (2hBG: - 7.26 mg/dl, IQR: - 21.6, 14.4, p = 0.024) at week 36. A high CD4 count and increased waist circumference were associated with 2hBG increase at week 36. CONCLUSION: We demonstrated a low incidence of T2DM in Ugandan ART-naïve patients receiving DTG. We also demonstrated that longitudinal changes in BG were independent of conventional risk factors of T2DM in the first 48 weeks of therapy. Restricting the use of dolutegravir in Ugandan ART naïve patients perceived to be high risk for diabetes mellitus may be unwarranted.

Prevalence of sero-markers and non-invasive assessment of liver cirrhosis in patients with Hepatitis B virus infection in Freetown, Sierra Leone: a cross-sectional study.

BACKGROUND: Hepatitis B virus (HBV) is a major global health problem. Although sub-Saharan Africa has a high proportion of the global burden of HBV, the epidemiology and clinical features of HBV in this region are poorly characterized, and access to diagnostic and treatment services remain limited. METHODS: We conducted a retrospective study of HBV-infected children and adults of all age groups who were evaluated at public and private health facilities in Freetown, Sierra Leone between January 2017 and January 2019. We assessed their clinical presentation, HBV sero-markers, stages of liver disease, prevalence of cirrhosis by non-invasive tools, and the proportion of treatment eligible patients using the criteria recommended by the World Health Organization's 2015 treatment guidelines for HBV. Logistic regression was used to identify predictors of liver cirrhosis. RESULTS: 163 HBV patients included in the study, with mean age 32.6 years and 65.0% (106) being males. Most (84.0%) were asymptomatic at presentation. The majority (69.9%) were classified as having HBeAg-negative chronic infection (or inactive HBsAg carrier phase), 24.5% were in the HBeAg-negative immune active phase, 3.1% had HBeAg positive hepatitis, and 2.5% were HBsAg negative. The median Aspartate aminotransferase to Platelet Ratio (APRI) and Fibrosis-4 (FIB-4) scores were 0.37 and 0.80, respectively. The prevalence of cirrhosis was 7.6% and 6.2%, estimated by the APRI and FIB-4 scores, respectively. About 20.0% of patients were eligible for treatment with antiviral agents. Based on APRI scores, the presence of any symptom [adjusted odds ratio (aOR) 20.0, 95% confidence interval (CI) (4.1-85.9); p < 0.001], elevated direct bilirubin [aOR 12.1, 95% CI (1.9-63.0); p = 0.003], and elevated total bilirubin [aOR 16.1, 95% CI (3.2-80.8); p = 0.001] were independent predictors of cirrhosis. CONCLUSION: Although most patients with HBV infection were asymptomatic, the prevalence of liver cirrhosis and proportion of patients requiring antiviral treatment were substantial. This small study from a hyperendemic setting in Sierra Leone suggests that routine population-based screening may increase early detection and linkage of HBV patients to care before development of complications. Larger studies are needed to confirm our findings.

Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone.

OBJECTIVES: The aim of this study was to assess the prevalence of HIV drug resistance (HIVDR) in HIV-infected ART-naive and -experienced patients in Sierra Leone. PATIENTS AND METHODS: We conducted a cross-sectional study of HIV-positive adults aged ≥18 years at Connaught Hospital in Freetown, Sierra Leone in November 2017. Sequencing was performed in the reverse transcriptase, protease and integrase regions, and interpreted using the Stanford HIVDR database and WHO 2009 mutation list. RESULTS: Two hundred and fifteen HIV-infected patients were included (64 ART naive and 151 ART experienced). The majority (66%) were female, the median age was 36 years and the median ART exposure was 48 months. The majority (83%) were infected with HIV-1 subtype CRF02_AG. In the ART-naive group, the pretreatment drug resistance (PDR) prevalence was 36.7% (14.2% to NRTIs and 22.4% to NNRTIs). The most prevalent PDR mutations were K103N (14.3%), M184V (8.2%) and Y181C (4.1%). In the ART-experienced group, 64.4% harboured resistance-associated mutations (RAMs) and the overall prevalence of RAMs to NRTIs and NNRTIs was 85.2% (52/61) and 96.7% (59/61), respectively. The most prevalent RAMs were K103N (40.7%), M184V (28.8%), D67N (15.3%) and T215I/F/Y (15.3%). Based on the genotypic susceptibility score estimates, 22.4% of ART-naive patients and 56% of ART-experienced patients were not susceptible to first-line ART used in Sierra Leone. CONCLUSIONS: A high prevalence of circulating NRTI- and NNRTI-resistant variants was observed in ART-naive and -experienced HIV-1-infected patients in Sierra Leone. This necessitates the implementation of HIVDR surveillance programmes to inform national ART guidelines for the treatment and monitoring of HIV-infected patients in Sierra Leone.

Causes of hospitalization and predictors of HIV-associated mortality at the main referral hospital in Sierra Leone: a prospective study.

BACKGROUND: HIV infection is a growing public health problem in Sierra Leone and the wider West Africa region. The countrywide HIV prevalence was estimated at 1.7% (67,000 people), with less than 30% receiving life-saving ART in 2016. Thus, HIV-infected patients tend to present to health facilities late, with high mortality risk. METHODS: We conducted a prospective study of HIV inpatients aged ≥15 years at Connaught Hospital in Freetown-the main referral hospital in Sierra Leone-from July through September 2017, to assess associated factors and predictors of HIV-related mortality. RESULTS: One hundred seventy-three HIV inpatients were included, accounting for 14.2% (173/1221) of all hospital admissions during the study period. The majority were female (59.5%, 70/173), median age was 34 years, with 51.4% (89/173) of them diagnosed with HIV infection for the first time during the current hospitalization. The most common admitting diagnoses were anemia (48%, 84/173), tuberculosis (24.3%, 42/173), pneumonia (17.3%, 30/173) and diarrheal illness (15.0%, 26/173). CD4 count was obtained in 64.7% (112/173) of patients, with median value of 87 cells/µL (IQR 25-266), and was further staged as severe immunosuppression: CD4 < 100 cells/µL (50%, 56/112); AIDS: CD4 < 200 cells/µL (69.6%, 78/112); and late-stage HIV disease: CD4 < 350 cells/µL (83%, 93/112). Fifty-two patients (30.1%, 52/173) died during hospitalization, 23% (12/52) of them within the first week. The leading causes of death were anemia (23.1%, 12/52), pneumonia (19.2%, 10/52), diarrheal illness (15.4%, 8/52) and tuberculosis (13.6%, 7/52). Neurological symptoms, i.e., loss of consciousness (p = 0.04) and focal limb weakness (p = 0.04); alcohol use (p = 0.01); jaundice (p = 0.02); cerebral toxoplasmosis (p = 0.01); and tuberculosis (p = 0.04) were significantly associated with mortality; however, only jaundice (AOR 0.11, 95% CI [0.02-0.65]; p = 0.01) emerged as an independent predictor of mortality. CONCLUSION: HIV-infected patients account for a substantial proportion of admissions at Connaught Hospital, with a high morbidity and in-hospital mortality burden. These findings necessitate the implementation of specific measures to enhance early HIV diagnosis and expand treatment access to all HIV-infected patients in Sierra Leone.

Risk Stratification of Advanced Fibrosis in Patients With Human Immunodeficiency Virus and Hepatic Steatosis Using the Fibrosis-4, Nonalcoholic Fatty Liver Disease Fibrosis, and BARD Scores.

Background: Nonalcoholic fatty liver disease (NAFLD) and subsequent progression to fibrosis is increasingly prevalent in people with HIV (PWH). We used noninvasive methods to stratify risk and identify associated factors of advanced fibrosis in PWH with NAFLD. Methods: We conducted a retrospective study of PWH in our clinic from 2005 to 2022. We used liver imaging or biopsy reports to identify cases of hepatic steatosis after excluding specified etiologies. We used the Fibrosis-4 (FIB-4), NAFLD Fibrosis (NFS), and body mass index, aspartate transaminase/alanine transaminase ratio, and diabetes score scores to stratify fibrosis. We used logistic regression to identify factors associated with advanced fibrosis. Results: Among 3959 PWH in care, 1201 had available imaging or liver biopsies. After exclusions, 114 of 783 PWH had evidence of hepatic steatosis (14.6%). Most were male (71.1%), with a median age of 47 years, and median body mass index of 30.1 kg/m2. Approximately 24% had lean NAFLD (ie, body mass index < 25 kg/m2). Based on the FIB-4 and NFS, 34 (29.8%) and 36 (31.6%) had advanced fibrosis, whereas 1 in 4 had low risk of fibrosis based on FIB-4, NFS, and BARD scores. In adjusted analysis using FIB-4, advanced fibrosis was associated with age > 45 years (adjusted odds ratio, 6.29; 95% confidence interval, 1.93-20.50) and hypoalbuminemia (adjusted odds ratio, 9.45; 95% confidence interval, 2.45-32.52) in addition to elevated transaminases and thrombocytopenia, whereas using the NFS did not identify associations with advanced fibrosis. Conclusions: We found 14.6% of PWH had NAFLD, with 1 in 3 having advanced fibrosis. Our study provides practical insights into fibrosis risk stratification in HIV primary care settings.

Associations between post-acute sequelae of SARS-CoV-2, COVID-19 vaccination and HIV infection: a United States cohort study.

Background: People with HIV (PWH) are at higher risk of complications from acute COVID-19, but their risk of subsequent post-acute sequelae of SARS-CoV2 (PASC) remains unclear. Although vaccination is protective of PASC among survivors in the general population, its effectiveness in PWH has not been explored. Methods: We used the TriNetX health research database to identify patients with and without HIV aged ≥18 years with confirmed SARS-CoV-2 between January 1, 2020 and July 20, 2023. We employed 1:1 propensity score matching to balance HIV and non-HIV cohorts based on demographics and key comorbidities. The primary outcomes accessed odds of PASC and mortality and secondary outcomes assessed odds of PASC and mortality by vaccination status. PASC was defined as new-onset conditions ≥ 28 days after COVID-19 diagnosis. We reported odd ratios (OR) of outcomes with 95% confidence intervals (CI), with statistical significance set at p < 0.05. Results: Of 3,029,340 people with confirmed SARS-CoV-2 infection, 0.5% (n=13,214) were PWH, with 7.5% of PWH (n=989) vaccinated. After 28 days post-COVID-19, PWH had higher odds of mortality compared with their non-HIV counterparts (OR 1.22, 95% CI 1.06-1.40) and developing new-onset HTN (OR 1.18, 95% CI 1.03-1.36), heart disease (OR 1.35 95% CI 1.18-1.54), malignancy (OR 1.49, 95% CI 1.22-1.81), and mental disorders (OR 1.62, 95% CI 1.42-1.85). Furthermore, vaccinated PWH had significantly lower odds of death (OR 0.63, 95% CI 0.42-0.93) and new-onset PASC outcomes: DM (OR 0.65, 95% CI 0.43-0.99), heart disease (OR 0.58, 95% CI 0.4-0.85), mental disorders (OR 0.66, 95% CI 0.43-1.00), fatigue (OR 0.82, 95% CI 0.67-0.98), respiratory (OR 0.82, 95% CI 0.70-0.95) and gastrointestinal symptoms (OR 0.78, 95% CI 0.67-0.90). Conclusion: HIV-positive status increased PASC odds, while COVID-19 vaccination reduced PASC and all-cause mortality risks in PWH.

Time to blood pressure control and predictors among patients receiving integrated treatment for hypertension and HIV based on an adapted WHO HEARTS implementation strategy at a large urban HIV clinic in Uganda.

In this cohort study, we determined time to blood pressure (BP) control and its predictors among hypertensive PLHIV enrolled in integrated hypertension-HIV care based on the World Health Organization (WHO) HEARTS strategy at Mulago Immunosuppression Clinic in Uganda. From August 2019 to March 2020, we enrolled hypertensive PLHIV aged ≥ 18 years and initiated Amlodipine 5 mg mono-therapy for BP (140-159)/(90-99) mmHg or Amlodipine 5 mg/Valsartan 80 mg duo-therapy for BP ≥ 160/90 mmHg. Patients were followed with a treatment escalation plan until BP control, defined as BP < 140/90 mmHg. We used Cox proportional hazards models to identify predictors of time to BP control. Of 877 PLHIV enrolled (mean age 50.4 years, 62.1% female), 30% received mono-therapy and 70% received duo-therapy. In the monotherapy group, 66%, 88% and 96% attained BP control in the first, second and third months, respectively. For patients on duo-therapy, 56%, 83%, 88% and 90% achieved BP control in the first, second, third, and fourth months, respectively. In adjusted Cox proportional hazard analysis, higher systolic BP (aHR 0.995, 95% CI 0.989-0.999) and baseline ART tenofovir/lamivudine/efavirenz (aHR 0.764, 95% CI 0.637-0.917) were associated with longer time to BP control, while being on ART for >10 years was associated with a shorter time to BP control (aHR 1.456, 95% CI 1.126-1.883). The WHO HEARTS strategy was effective at achieving timely BP control among PLHIV. Additionally, monotherapy anti-hypertensive treatment for stage I hypertension is a viable option to achieve BP control and limit pill burden in resource limited HIV care settings.

Risk Stratification of Advanced Fibrosis in HIV Patients With Hepatic Steatosis Using the NAFLD Fibrosis and BARD Scores.

Background: Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent in people with HIV (PWH), yet the risk factors for disease progression are poorly understood, due to inadequate surveillance. We employed non-invasive methods to estimate the prevalence and associated factors of advanced NAFLD in PWH. Methods: We conducted a retrospective study of PWH enrolled in our clinic from 2005 to 2022. We employed imaging (ultrasound, computer tomography, magnetic resonance imaging, and transient elastography) or biopsy reports to identify cases of hepatic steatosis. We excluded patients with harmful alcohol use, hepatitis B or C infection, and other specified etiologies. We used the NAFLD Fibrosis Score (NFS), BARD Score, AST to Platelet Index (APRI), and Fibrosis-4 (FIB-4) Score to stratify fibrosis. We used logistic regression to identify predictors of advanced fibrosis. Results: Among 3959 PWH in care, 1201 had available imaging or liver biopsies. After exclusions, 114 of the remaining 783 had evidence of hepatic steatosis (prevalence 14.6%). The majority were male (71.1%), with mean age 46.1 years, and mean body mass index (BMI) 31.4 ± 8.1 kg/m2. About 24% had lean NAFLD (BMI < 25 kg/m2). Based on the NFS, 27.2% had advanced fibrosis, which was corroborated by estimates from the other scores. In adjusted regression analysis, advanced fibrosis was associated with BMI > 35 kg/m2 (4.43, 1.27-15.48), thrombocytopenia (4.85, 1.27-18.62) and hypoalbuminemia (9.01, 2.39-33.91). Conclusion: We found a NAFLD prevalence of 14.6%, with 27.2% of cases having advanced fibrosis. Our study provides practical insights into the surveillance of NAFLD in PWH.

Should dolutegravir always be withheld in people with HIV on dolutegravir with incident diabetes mellitus? A case report.

Dolutegravir (DTG), an integrase strand transfer inhibitor is currently the recommended first and second line anti-retroviral therapy (ART) anchor agent by the World Health Organization. This followed widespread reports of primary resistance to non-nucleoside reverse transcriptase inhibitors. Despite its very good side effect profile, there have been multiple case reports of ART experienced patients developing hyperglycemia within weeks to a few months after switching to DTG preceded by weight loss. At population level, however, dolutegravir as well as other integrase inhibitors have been demonstrated to have a reduced risk of incident diabetes mellitus (T2DM) compared to other HIV drug classes. Following multiple similar reports of accelerated hyperglycemia in Uganda during the first pilot year of DTG use, the Uganda Ministry of Health recommended withholding dolutegravir in all patients who develop diabetes. Whether this recommendation should be applied to all patients with incident T2DM remains to be demonstrated. We present a clinical case of an HIV positive ART naïve man who was diagnosed with T2DM after 36 weeks on dolutegravir. We describe changes in blood glucose, glycated hemoglobin, insulin resistance and pancreatic beta cell function before and after withholding DTG. We demonstrated that he was phenotypically different from the reported cases of accelerated hyperglycemia and he continued to have worsening insulin resistance despite withholding DTG. His blood glucose improved with dietary T2DM management. It is possible he had an inherent risk of developing T2DM independent of his exposure to DTG. This put in question whether DTG should universally be withheld in PLHIV with incident T2DM in Uganda.

Prevalence of Cardiometabolic Disease Risk Factors in People With HIV Initiating Antiretroviral Therapy at a High-Volume HIV Clinic in Kampala, Uganda.

Background: Cardiometabolic diseases are a leading cause of HIV-related morbidity and mortality, yet routine screening is not undertaken in high-burden countries. We aimed to assess the prevalence and risk factors of the metabolic syndrome (MetS) and its components in adult Ugandan people with HIV (PWH) initiating dolutegravir-based antiretroviral therapy (ART). Methods: We conducted a cross-sectional study using baseline sociodemographic and clinical data of PWH aged ≥18 years enrolled in the Glucose metabolism changes in Ugandan HIV patients on Dolutegravir (GLUMED) study from January to October 2021. MetS was defined as having ≥3 of the following: abdominal obesity, hypertension (HTN), hyperglycemia, elevated triglycerides, and low high-density lipoprotein cholesterol. Multiple logistic regression was used to assess associations between potential risk factors and MetS and its components. Results: Three hundred nine PWH were analyzed (100% ART-naïve, 59.2% female, median age 31 years, and median CD4 count 318 cells/mm3). The prevalence of MetS was 13.9%. The most common cardiometabolic condition was dyslipidemia (93.6%), followed by abdominal obesity (34.0%), hyperglycemia (18.4%), and HTN (8.1%). In adjusted analysis, MetS was associated with age >40 years (adjusted odds ratio [aOR], 3.33; 95% CI, 1.45-7.67) and CD4 count >200 cells/mm3 (aOR, 3.79; 95% CI, 1.23-11.63). HTN was associated with age >40 years (aOR, 2.96; 95% CI, 1.32-6.64), and dyslipidemia was associated with urban residence (aOR, 4.99; 95% CI, 1.35-18.53). Conclusions: Cardiometabolic risk factors were common in this young Ugandan cohort of PWH initiating dolutegravir-based ART, underscoring the need for programmatic implementation of surveillance and management of comorbidities in Uganda and similar settings.