COVID-19 Severity and COVID-19-Associated Deaths Among Hospitalized Patients with HIV Infection - Zambia, March-December 2020.

The effect of HIV infection on COVID-19 outcomes is unclear. Studies in South Africa (1) and the United Kingdom (2) found an independent association between HIV infection and COVID-19 mortality; however, other studies have not found an association between poor COVID-19 outcomes and either HIV status among hospitalized patients (3-5) or HIV-associated factors such as CD4 count, viral load, or type of antiretroviral therapy (ART) (6). The effect of HIV infection on COVID-19 outcomes remains an urgent question in sub-Saharan Africa, where many countries are experiencing dual HIV and COVID-19 epidemics, and capacity to treat severe COVID-19 is limited. Using data from patients with probable or confirmed COVID-19 admitted to specialized treatment centers during March-December 2020 in Zambia, the Zambian Ministry of Health and CDC assessed the relationship between HIV infection and severe COVID-19 and COVID-19-associated death. Among 443 patients included in the study, 122 (28%) were HIV-positive, and of these, 91 (89%) were receiving ART at the time of hospitalization. HIV status alone was not significantly associated with severe COVID-19 at admission or during hospitalization or with COVID-19-associated death. However, among HIV-positive persons, those with severe HIV disease were more likely to develop severe COVID-19 and were at increased risk for COVID-19-associated death. Ensuring that persons maintain HIV disease control, including maintaining ART continuity and adherence, achieving viral suppression, and addressing and managing underlying medical conditions, could help reduce COVID-19-associated morbidity and mortality in sub-Saharan Africa.

Gut microbiota dependant trimethylamine N-oxide and hypertension.

The human gut microbiota environment is constantly changing and some specific changes influence the host's metabolic, immune, and neuroendocrine functions. Emerging evidence of the gut microbiota's role in the development of cardiovascular disease (CVD) including hypertension is remarkable. There is evidence showing that alterations in the gut microbiota and especially the gut-dependant metabolite trimethylamine N-oxide is associated with hypertension. However, there is a scarcity of literature addressing the role of trimethylamine N-oxide in hypertension pathogenesis. In this review, we discuss the impact of the gut microbiota and gut microbiota dependant trimethylamine N-oxide in the pathogenesis of hypertension. We present evidence from both human and animal studies and further discuss new insights relating to potential therapies for managing hypertension by altering the gut microbiota.

Hypertension and human immunodeficiency virus: A paradigm for epithelial sodium channels?

Hypertension is a risk factor for end organ damage and death and is more common in persons with HIV compared to the general population. Several mechanisms have been studied in the pathogenesis of hypertension. Current evidence suggests that the epithelial sodium channel (ENaC) plays a key role in regulating blood pressure through the transport of sodium and water across membranes in the kidney tubules, resulting in retention of sodium and water and an altered fluid balance. However, there is scarcity of information that elucidates the role of ENaC in HIV as it relates to increasing the risk for development or pathogenesis of hypertension. This review summarized the evidence to date implicating a potential role for altered ENaC activity in contributing to hypertension in patients with HIV.

Sex differences in hypertension among people living with HIV after initiation of antiretroviral therapy.

Background: Hypertension is common in people living with HIV (PLWH) on antiretroviral therapy (ART). In the general population and in experimental animal models, the incidence of hypertension is greater in males than in females, especially during the premenopausal period. However, it is not known whether there are sex differences in hypertension associated with HIV and ART, and the factors contributing to incident hypertension among PLWH have not been well characterized. In this study, we aimed to determine the time course, sex differences and factors associated with incident hypertension in PLWH initiating ART. Methods and results: We conducted a retrospective study in which we used programmatic data from the ART registry to identify sex differences in the determinants of incident hypertension among PLWH initiating the ART regimen from Livingstone University Teaching Hospital in Zambia and followed for 8 years. Males developed hypertension earlier, 2 years after initiating ART, compared to 6 years in females. In multivariable analysis, increasing age, baseline systolic blood pressure and baseline mean arterial pressure (MAP) were associated with increased risk for developing incident hypertension. Also, participants who switched to the integrase strand transfer inhibitor, dolutegravir (DTG) or the protease inhibitor, lopinavir boosted with ritonavir were 2 and 3 times more likely to develop hypertension when compared to those on non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, these relationships were abrogated by sex, as self-reported male sex was the major contributor in predicting incident hypertension. While none of the factors remained significantly associated with incident hypertension upon multivariate analysis among females, body mass index (BMI), and use of protease inhibitors remained strongly associated with hypertension among males. Conclusion: Our results indicate that the use of protease inhibitors and BMI are important predictors of incident hypertension among males. Thus, blood pressure and BMI should be closely monitored, particularly in males living with HIV on protease inhibitors. In addition, identifying specific factors that protect females from developing hypertension early is important but remains to be determined.

COVID-19 Vaccine Effectiveness Against Progression to In-Hospital Mortality in Zambia, 2021-2022.

Background: Coronavirus disease 2019 (COVID-19) vaccines are highly effective for reducing severe disease and mortality. However, vaccine effectiveness data are limited from Sub-Saharan Africa. We report COVID-19 vaccine effectiveness against progression to in-hospital mortality in Zambia. Methods: We conducted a retrospective cohort study among admitted patients at 8 COVID-19 treatment centers across Zambia during April 2021 through March 2022, when the Delta and Omicron variants were circulating. Patient demographic and clinical information including vaccination status and hospitalization outcome (discharged or died) were collected. Multivariable logistic regression was used to assess the odds of in-hospital mortality by vaccination status, adjusted for age, sex, number of comorbid conditions, disease severity, hospitalization month, and COVID-19 treatment center. Vaccine effectiveness of ≥1 vaccine dose was calculated from the adjusted odds ratio. Results: Among 1653 patients with data on their vaccination status and hospitalization outcome, 365 (22.1%) died. Overall, 236 (14.3%) patients had received ≥1 vaccine dose before hospital admission. Of the patients who had received ≥1 vaccine dose, 22 (9.3%) died compared with 343 (24.2%) among unvaccinated patients (P < .01). The median time since receipt of a first vaccine dose (interquartile range) was 52.5 (28-107) days. Vaccine effectiveness for progression to in-hospital mortality among hospitalized patients was 64.8% (95% CI, 42.3%-79.4%). Conclusions: Among patients admitted to COVID-19 treatment centers in Zambia, COVID-19 vaccination was associated with lower progression to in-hospital mortality. These data are consistent with evidence from other countries demonstrating the benefit of COVID-19 vaccination against severe complications. Vaccination is a critical tool for reducing the consequences of COVID-19 in Zambia.

Prevalence of low high-density lipoprotein among young adults receiving antiretroviral therapy in Zambia: An opportunity to consider non-communicable diseases in resource-limited settings.

BACKGROUND: With the introduction of effective antiretroviral therapy (ART), people living with HIV (PLWH) are surviving longer and are at risk for developing metabolic abnormalities that contribute to cardiovascular disease (CVD). In Sub-Saharan Africa (SSA), there is a paucity of epidemiological data on lipid profiles among young adults receiving ART. This study aimed to estimate the prevalence of low high-density lipoprotein cholesterol (HDL-c), a cardioprotective lipid class, and whether it differed by age among adults on ART in Livingstone, Zambia. METHODS: From April to December 2019, we conducted a cross-sectional study of 597 PLWH [n = 58 aged 18-24 years (young adults); n = 539 aged ≥25 years (adults)] on ART for ≥6 months. Data collected included demographic and lifestyle information, anthropometrics, viral load (VL), CD4 count, blood pressure, lipid profiles and fasting/random blood glucose. Clinical measures were defined as: low HDL-c [<1.0 mmol/L for men, <1.3 for women], increased waist circumference (WC) [≥94 cm for men, ≥80 cm for women], high triglycerides (TG) [≥1.7 mmol/l], and virological failure (VF) [VL ≥1000 copies/µl]. We used logistic regression to examine the association between age and low HDL-c after adjusting for multiple variables. RESULTS: Among the young adults, 60% (35/58) were women, median (25th, 75th percentile) age 21 years (18, 23), and median time on ART 116 months (60, 144). Among adults, 63% (342/539) were women, median age 46 years (40, 53) and median time on ART 108 months (60, 144). Young adults had a lower CD4 count compared to adults (median, 492 vs. 568 cells/µL, p = 0.010) and higher prevalence of VF (29% vs. 17%, p = 0.016). In young adults, prevalence of low HDL-c was significantly higher than in adults (63 vs. 38%, p<0.001). A high proportion of young adults (75%) and adults (58%) with low HDL-c were on dolutegravir (DTG)-based ART regimens. After adjusting for sex, duration on ART, WC, body mass index, ART regimen, VF, CD4 count, low density lipoprotein cholesterol, blood pressure and smoking, young adults were significantly more likely than adults to have low HDL-c (odds ratio 2.93; 95% confidence interval 1.46-5.86). CONCLUSION: Low HDL-c is highly prevalent among young adult with HIV in SSA independent of other risk factors for metabolic derangements. Lipid abnormalities among young PLWH may contribute to the early development of cardiovascular diseases in this population. This highlights the need to consider low HDL-c in the quest to reduce CVD risk among young adults on ART in SSA.

Pernicious Anemia and Vitiligo in an HIV Patient: An Unfamiliar Case Presentation.

Pernicious anemia (PA) is a rarely considered cause of anemia in HIV-infected population and is seldom on the list of differential diagnoses. However, PA can have serious consequences if misdiagnosed or left untreated. We present the case of a 38-year-old HIV-positive man who was diagnosed with PA, which was preceded by a one-year history of vitiligo. Our case is a reminder for clinicians to have a high index of suspicion for an autoimmune process as a potential cause of anemia in HIV-infected individuals.

Progressive respiratory distress in a 42-year-old HIV-positive woman with systemic lupus erythematosus.

BACKGROUND: Identifying and treating the cause of pulmonary symptoms in HIV patients with underlying systemic lupus erythematosus (SLE) can be very challenging. Delays in diagnosing active SLE in HIV patients can lead to significant morbidity and even mortality. We report the case of an HIV-positive woman with SLE who presented with severe respiratory distress. CASE PRESENTATION: A 42-year-old HIV-positive woman presented with a 7-month history of anorexia, progressive dyspnoea, and a productive cough. She had been put on treatment for pulmonary tuberculosis and pneumocystis jiroveci pneumonia for several months by the referring hospital without any significant improvement in her symptoms. Her initial laboratory investigations showed highly elevated d-dimer test results but confirmatory investigations for pulmonary embolism proved otherwise. An autoimmune screen revealed highly positive antinuclear antibody and anti-double-stranded DNA tests, and she responded very well to SLE treatment. CONCLUSIONS: Our case represents a situation where two diseases with antagonizing pathways of disease pathogenesis occur concurrently in the same patient. SLE is usually not among the differential diagnoses in HIV patients with respiratory distress. Management of patients with both SLE and HIV is also very challenging because improvement in one condition can lead to worsening of the other. Despite opportunistic infections being the likely cause of pulmonary symptoms in HIV patients, clinicians are encouraged to have a high index of suspicion for autoimmune interstitial lung disease in these patients.