Tom Heller

To close gaps in implementing care of people with hepatitis B virus (HBV) infection in resource‐limited settings, we evaluated the accuracy of a novel liver point‐of‐care ultrasound (POCUS) protocol for hepatitis (PUSH) among front‐line non‐radiology healthcare workers in Zambia. At University Teaching Hospital in Lusaka, Zambia, from March to June 2024, we trained four nurses and six physicians with experience in HBV management, but not in ultrasound (US), in the PUSH protocol, which includes visualizing the liver in three windows (epigastric, subcostal and right transcostal) to identify cirrhosis‐suggestive features and liver lesions suspicious for hepatocellular carcinoma (HCC). Then, consecutive adult participants with chronic hepatitis B (PWHB) alone or HBV/HIV coinfection underwent PUSH with operators blinded to clinical data. We evaluated the accuracy of PUSH for significant fibrosis and cirrhosis using transient elastography (TE) as the reference standard test (RST) and for liver lesions that were possible HCC using a comprehensive abdominal ultrasound by an experienced radiographer as the RST. Nonparametric analysis of the receiver operating curve (ROC) for PUSH was adjusted for operator type (doctor vs. nurse), sex and HIV status. Among 197 PWHBs analysed, 69.5% were taking HBV antivirals and 27.9% had HBV/HIV. According to RSTs, 17.7% of PWHBs had significant fibrosis, 11.6% had cirrhosis and 3.5% had liver lesions. PUSH had low accuracy for significant fibrosis, with sensitivity of 8.3% (17.5–41.4), specificity of 100.0% (96.1–100) and an area under the curve (AUROC) of 0.54 (0.43–0.65), moderate accuracy for cirrhosis, with sensitivity of 60.9% (38.5–80.3), specificity of 97.7% (94.2–99.4) and AUROC of 0.79 (0.69–0.89), and higher accuracy for liver lesions, with 85.7% (42.1–99.6) sensitivity, 98.4% (95.5–99.7) specificity, AUROC of 0.92 (0.78–1.00). After an expedited training, front‐line nurses and physicians treating HBV in Zambia were able to use PUSH to diagnose cirrhosis with moderate accuracy and liver lesions with high accuracy, although confidence intervals around performance estimates were wide. Liver POCUS including PUSH may be useful in HBV management when laboratory systems and TE are lacking.

Background: Enlarged lymph nodes (LN) pose diagnostic challenges for people with HIV (PWH). While tuberculosis (TB) is a common cause in low-income settings, lymphomas and Kaposi’s sarcoma must also be considered. Ultrasound and symptoms cannot distinguish between these conditions, and histology is often needed, but limited resources in low-income countries restrict sampling. To minimize the need for excisional biopsies, we introduced an algorithm for ultrasound-guided core-needle biopsies (CNB) after negative fine-needle aspiration (FNA) results by Xpert-Ultra (Cepheid, USA). Methods: At the Lighthouse clinic in Lilongwe, Malawi, patients with peripheral lymphadenopathy underwent an ultrasound-guided FNA. Negative Xpert-Ultra results prompted CNB using Tru-Cut needles, with samples sent for pathology. We retrospectively analyzed 12 months of cross-sectional data, including histology results and abdominal ultrasound findings. Results: In 2024, 53 CNBs were performed, 96%in PWH. No significant complications were observed. A conclusive diagnosis was reached in 77% of cases, with the most common diagnoses being hematological malignancies (54%), reactive LN (15%), Kaposi’s sarcoma (12%) and metastatic carcinoma (10%). Infections, including granulomatous inflammation were found in 10% of cases. Hypoechoic spleen lesions were more frequent in patients with hematological diseases (p=0.03). Conclusion: Ultrasound-guided CNB of enlarged peripheral LN is a safe, effective addition to routine ART clinics. After negative Xpert-Ultra FNA, hematological malignancies were common. Abdominal ultrasound findings were frequently abnormal overall and hypoechoic spleen lesions were more common in patients with hematological abnormalities.

PURPOSE: Few data describe the modern epidemiology of pediatric HIV-associated cancers in sub-Saharan Africa, home to over 80% of the world's children living with HIV. This study evaluated the incidence of cancers among these children over 15 years after widespread antiretroviral therapy (ART) adoption in Malawi. METHODS: We conducted a retrospective population-based cohort study leveraging multiple independent data sources comprehensive of all cancer diagnoses among children living with HIV in Northern and Central Malawi between 2010 and 2024. HIV-associated cancers were defined as those cancers with well-established epidemiologic associations with HIV. Cumulative incidence and average annual percent change were estimated using joinpoint regression. Next, we conducted a subcohort analysis within the country's largest pediatric HIV clinic to evaluate cancer risk factors using log-binomial regression. RESULTS: Among 1,686 pediatric cancer diagnoses, 184 (10.9%) occurred in children with HIV. Kaposi sarcoma (KS) accounted for 96% of cases. The cumulative incidence of HIV-associated malignancies fell from 4.7 cases per million children in 2010 to 1.2 per million in 2024, representing an 84% decline from its peak in 2013 and an average annual percent decline of 13% ( P < .001). KS dropped from the third- to seventh-most common childhood cancer in the region. Notably, 58% of affected children were ART-naïve at diagnosis. Initiating ART in infancy reduced the risk of KS by 69% ( P < .001). Other HIV-associated cancers were rare, comprising 0.4% of all cases diagnosed. CONCLUSION: National ART expansion substantially reduced pediatric HIV-associated cancers in Malawi, achieving declines comparable with those seen in high-income countries. Sustained early diagnosis and ART linkage remain essential to sustain progress.

Background: Most first-line antiretroviral therapy (ART) regimes in Sub-Saharan Africa contain tenofovir disoproxil fumarate (TDF) which has a nephrotoxic potential. Baseline renal function assessment is not feasible in many settings and therefore not required prior to starting ART according to Malawian guidelines. We assessed renal function over 36 months in people living with HIV (PLHIV) starting TDF-based ART at Lighthouse Clinic, Lilongwe, Malawi. Methods: Data on demographics, medical history, laboratory values, WHO stage, and anthropometric measures were collected at study entry and during visits at 1, 3, 6 months, and every 6 months until month 36. The main outcome of the study was renal function, defined by the estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI equation. Descriptive statistics and multivariable linear regression analysis were performed. Results: A baseline creatinine value was available for 1,430 PLHIV (57% female, mean age ± SD 36.0 ± 9.3 years). Of these, 443 PLHIV (62% female) were observed until month 36. Factors associated with changes in eGFR over time included baseline log-transformed eGFR (coefficient = −0.787; p < 0.001), MAP at baseline, and initial WHO clinical HIV stage. The overall trend in eGFR categories indicated a shift towards lower classes. Conclusions: In this large cohort of PLHIV, TDF did not result in a decline in eGFR. Indeed, an unexpected trend of improved renal function was observed. Even though findings need to be interpreted with caution due to considerable attrition, our results suggest TDF can be administered safely in resource-limited settings where ART decisions are frequently made without pre-treatment renal assessment.

The Southern African Journal of HIV Medicine is focused on HIV/AIDS treatment, prevention and related topics relevant to clinical and public health practice. The purpose of the journal is to disseminate original research results and support high-level learning related to HIV Medicine. It publishes original research articles, editorials, case reports/case series, reviews of state-of-the-art clinical practice and correspondence.

Kaposi sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV-8), is the primary etiologic cause of Kaposi sarcoma (KS) and KSHV Inflammatory Cytokine Syndrome (KICS). Patients with KICS demonstrate symptoms of systemic inflammation, high KSHV viral load, elevation of inflammatory markers, and increased mortality. Management requires rapid diagnosis, treatment of underlying HIV, direct treatment of KS, and addressing the hyperimmune response. While a case definition based on clinical presentation, imaging findings, laboratory values, KSHV viral load, and lymph-node biopsy has been proposed, some of the required investigations are frequently unavailable in resource-constrained settings. Due to these challenges, KICS likely remains underdiagnosed and undertreated in these settings. We report a case of a 19-year-old woman living with HIV, and intermittent adherence to her ART, who presented with hypotension and acute hypoxemic respiratory failure. She was found to have high KSHV and HIV viral loads, low CD4 count, anemia, thrombocytopenia, hypoalbuminemia, and elevated inflammatory markers. On bedside ultrasound, she was found to have bilateral pleural effusions, ascites, an enlarged spleen, and hyperechoic splenic lesions. The diagnosis of KICS was made based on this constellation of findings. Weighing the risk and benefits of steroid administration in KS patients, the patient was successfully treated by the continuation of ART and the initiation of paclitaxel chemotherapy and steroids. We propose an adapted case definition relevant to the resource-constrained context. Due to the dual burden of KSHV and HIV in sub-Saharan Africa, additional cases of KICS are likely, and this syndrome will contribute to the burden of early mortality in newly diagnosed HIV patients. Addressing the diagnostic and therapeutic challenges of KICS must be a part of the overall management of the HIV pandemic.

Background/Objectives: Kaposi sarcoma (KS) is a common lymphatic endothelial cancer among children with and without HIV in central and eastern Africa. Despite its clinical heterogeneity, its various clinical phenotypes are often grouped together in staging and treatment algorithms. Patients with KS tumor-associated edema, referring to hard, non-pitting lesions which often lead to chronic disability, represent a unique, understudied subgroup of children with KS. To continue our work defining the distinct phenotypes of pediatric KS, this study aimed to assess the clinical progression and outcomes of KS edema in children. Methods: A retrospective cohort study was conducted at Kamuzu Central Hospital in Lilongwe, Malawi, focusing on children diagnosed with KS edema between 2010 and 2023. Results: We identified 52 children with KS edema, representing 27% of all patients with KS. Initial chemotherapy resulted in a clinical response in 92% of patients, but 46% experienced relapse or disease progression with a median time to first relapse of 12 months. Multiple progressions were common, with 31% of patients experiencing two or more events. Event-free survival at two years was 32%, dropping to 24% at five years, while overall survival was 73% at two years and 57% at five years. Relapse was more common among patients with KS edema versus those without it (relative risk = 2.1; 95%CI, 1.4–3.2; p < 0.001). Eight patients (15%) relapsed with visceral disease, five of whom originally presented with KS edema alone. Conclusions: Patients with KS edema have a unique, relapsing-remitting pattern of disease with a high risk of relapse relative to other forms of KS with subsequent long-term mortality, even after initial positive treatment responses. Late relapse and mortality with visceral disease are possible even among children presenting initially with KS edema alone. Children with KS edema require long-term follow-up, and novel treatment approaches tailored towards preventing frequent relapse are needed.

: Miliary tuberculosis is a form of disseminated tuberculosis that can be difficult to detect when the classic pattern is absent on chest radiograph and advanced cross-sectional imaging is not readily available. While the focused assessment with sonography for HIV-associated tuberculosis (FASH) protocol for extrapulmonary tuberculosis emphasizes easy-to-teach findings, experienced sonographers may detect additional, subtler signs that can aid in diagnosis. We report a case of a 20-year-old man with miliary tuberculosis diagnosed on computed tomography of the chest. We describe subtle sonographic signs of disseminated tuberculosis including subpleural irregularities and comet-tail artifacts, a bright liver pattern, peritoneal nodules, and a nonspecific sponge spleen pattern. We then discuss important differential diagnoses for each finding. Knowledge of subtle sonographic signs outside of the FASH protocol can aid clinicians in detecting disseminated tuberculosis, including the miliary form, when advanced imaging may not be available.

Background: Chronic Hepatitis B (CHB) is prevalent worldwide and most related deaths occur in low-resource settings. Antiviral treatment of CHB is indicated in those with significant liver disease and markers of viral replication. However, recommended diagnostics such as elastography (a non-invasive imaging measure of fibrosis/cirrhosis) or HBV viral load are often lacking in these settings, which creates barriers to treatment. Point-of-care clinical B-mode ultrasound (US) has potential to overcome implementation barriers in HBV care programs in low-resource settings. Methods: We describe a Point-of-care US protocol for Hepatitis (“PUSH”) to check for signs of cirrhosis and hepatocellular carcinoma in the liver of people with CHB. We performed a prospective observational study applying the protocol, first by trainee clinicians and then by trainers, in consecutive patients referred to our clinic for CHB treatment eligibility assessment. All patients additionally underwent physical examination, liver function tests (LFTs) and platelet counts. We describe the PUSH training approach and performance of the protocol. Results: Four clinicians and 111 adult patients with HBV infection were included in the development of PUSH. Using US, liver complications of HBV were documented in 31 (27.9%) patients; including cirrhosis in 15 patients, HCC with cirrhosis in 13, and HCC without cirrhosis in 3. Patients with sonographic findings had significantly more clinical symptoms also their LFTs were higher and more frequently indicative for HBV treatment. Of 28 patients with sonographic diagnosis of cirrhosis, 23 (82.1%) showed a nodular liver surface, 24 (85.7%) a coarse echotexture, 20 (71.4%) scarce vessels, and 9 (32.1%) an enlarged caudate lobe. Overall concordance of the findings between assessment of trainees and experienced sonographers was high, ranging from 90 to 95%; trainees were not blinded to clinical and laboratory findings. Conclusion: Ultrasound can facilitate same-day initiation of antiviral therapy for chronic HBV monoinfection in a resource-limited setting and a streamlined protocol-driven liver ultrasound can be feasibly used by front line clinicians managing HBV.

Syphilis is a sexually transmitted infection caused by Treponema pallidum. It progresses in phases and undiagnosed disease can cause considerable morbidity. Tertiary syphilis causes the formation of gummas. Liver involvement is rarely described and usually limited to transaminase elevation during primary syphilis. We present a case of tertiary syphilis in an HIV patient. Microbiological, clinical, and radiological information were retrieved from the patient’s record. Gummatous syphilis is rarely described in the literature, and practicing physicians should be aware of its existence and include this manifestation in the differential diagnosis of patients with a positive serology and focal liver lesions.