The convergence of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) represents a considerable global public health challenge. The concurrent infection of HIV and TB in pregnant women not only intensifies the transmission of HIV from mother to fetus but also engenders adverse outcomes for maternal health, pregnancy, and infant well-being, necessitating the implementation of integrated strategies to effectively address and manage both diseases. In this article, we review the pathophysiology, clinical presentation, treatment, and management of HIV/TB coinfection during pregnancy, the postpartum period, and lactation and highlight the differences compared to the general population.

The evolution of antiretroviral therapies (ART) has tremendously improved the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH), which is currently similar to the general population. However, as PLWH are now living longer, they exhibit various comorbidities such as a higher risk of cardiovascular disease (CVD) and non-acquired immunodeficiency syndrome (AIDS)-defined malignancies. Clonal hematopoiesis (CH) is the acquisition of somatic mutations by the hematopoietic stem cells, rendering them survival and growth benefit, thus leading to their clonal dominance in the bone marrow. Recent epidemiologic studies have highlighted that PLWH have a higher prevalence of CH, which in turn is associated with increased CVD risk. Thus, a link between HIV infection and a higher risk for CVD might be explained through the induction of inflammatory signaling in the monocytes carrying CH mutations. Among the PLWH, CH is associated with an overall poorer control of HIV infection; an association that requires further mechanistic evaluation. Finally, CH is linked to an increased risk of progression to myeloid neoplasms including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which are associated with particularly poor outcomes among patients with HIV infection. These bidirectional associations require further molecular-level understanding, highlighting the need for more preclinical and prospective clinical studies. This review summarizes the current literature on the association between CH and HIV infection.

Importance: Commonly used risk assessment tools for cardiovascular disease might not be accurate for HIV-infected patients. Objective: We aimed to develop a model to accurately predict the 10-year cardiovascular disease (CV) risk of HIV-infected patients. Design: In this retrospective cohort study, adult HIV-infected patients seen at Boston Medical Center between March 2012 and January 2017 were divided into model development and validation cohorts. Setting: Boston Medical Center, a tertiary, academic medical center. Participants: Adult HIV-infected patients, seen in inpatient and outpatient setting. Main Outcomes and Measures: We used logistic regression to create a prediction risk model for cardiovascular events using data from the development cohort. Using a point-based risk-scoring system, we summarized the relationship between risk factors and cardiovascular disease (CVD) risk. We then used the area under the receiver operating characteristics curve (AUC) to evaluate model discrimination. Finally, we tested the model using a validation cohort. Results: 1914 individuals met the inclusion criteria. The model had excellent discrimination for CVD risk [AUC 0.989; (95% CI: 0.986–0.993)] and included the following 11 variables: male sex (95% CI: 2.53–3.99), African American race/ethnicity (95% CI: 1.50–3.13), current age (95% CI: 0.07–0.13), age at HIV diagnosis (95% CI: −0.10–(−0.02)), peak HIV viral load (95% CI: 9.89 × 10⁻⁷–3.00 × 10⁻⁶), nadir CD4 lymphocyte count (95% CI: −0.03–(−0.02)), hypertension (95% CI: 0.20–1.54), hyperlipidemia (95% CI: 3.03–4.60), diabetes (95% CI: 0.61–1.89), chronic kidney disease (95% CI: 1.26–2.62), and smoking (95% CI: 0.12–2.39). The eleven-parameter multiple logistic regression model had excellent discrimination [AUC 0.957; (95% CI: 0.938–0.975)] when applied to the validation cohort. Conclusions and Relevance: Our novel HIV-CARDIO-PREDICT Score may provide a rapid and accurate evaluation of CV disease risk among HIV-infected patients and inform prevention measures.

Mycobacterium tuberculosis ( Mtb) is one of the leading infectious causes of death worldwide. There is no available licensed therapeutic vaccine that shortens active tuberculosis (TB) disease drug treatment and prevents relapse, despite the World Health Organization’s calls. Here, we show that an intranasal DNA vaccine containing a fusion of the stringent response rel _Mtb gene with the gene encoding the immature dendritic cell-targeting chemokine, MIP-3α/CCL20, shortens the duration of curative TB treatment in immunocompetent mice. Compared to the first-line regimen for drug-susceptible TB alone, our novel adjunctive vaccine induced greater Rel _Mtb -specific T-cell responses associated with optimal TB control in spleen, blood, lungs, mediastinal lymph nodes, and bronchoalveolar lavage (BAL) fluid. These responses were sustained, if not augmented, over time. It also triggered more effective dendritic cell recruitment, activation, and colocalization with T cells, implying enhanced crosstalk between innate and adaptive immunity. Moreover, it potentiated a 6-month TB drug-resistant regimen, rendering it effective across treatment regimens, and also showed promising results in CD4+ knockout mice, perhaps due to enhanced Rel-specific CD8+ T-cell responses. Notably, our novel fusion vaccine was also immunogenic in nonhuman primates, the gold standard animal model for TB vaccine studies, eliciting antigen-specific T-cell responses in blood and BAL fluid analogous to those observed in protected mice. Our findings have critical implications for therapeutic TB vaccine clinical development in immunocompetent and immunocompromised populations and may serve as a model for defining immunological correlates of therapeutic vaccine-induced protection. One sentence summary: A TB vaccine shortens curative drug treatment in mice by eliciting strong TB-protective immune responses and induces similar responses in macaques.

Tuberculosis necrotic granulomas contain triglyceride-rich macrophages (foam cells) with reduced antimicrobial functions. We assessed the ability of 2 compounds to reduce the triglyceride content and Mycobacterium tuberculosis (Mtb) burden in infected human monocyte-derived macrophages and in the lungs of Mtb-infected C3HeB/FeJ mice: A-922500 (DGATi), an inhibitor of diacylglycerol O-acyltransferase 1, and LY2584702 (p70S6Ki), an inhibitor of p70 S6 kinase. DGATi and p70S6Ki significantly reduced the lipid content and bacillary burden in Mtb-infected macrophages. Each inhibitor reduced the cellular triglyceride content in bronchoalveolar lavage samples of Mtb-infected mice. After 6 weeks of treatment, p70S6Ki alone reduced the lung bacterial burden in Mtb-infected mice. However, DGATi alone and DGATi or p70S6Ki in combination with isoniazid did not reduce lung bacterial burden or alter lung inflammation. These findings provide further insight into the role of foam cells in tuberculosis pathogenesis and the utility of interventions targeting these cell populations as adjunctive host-directed therapies.

Lengthy tuberculosis (TB) treatment is required to address the ability of a subpopulation of persistent Mycobacterium tuberculosis ( Mtb ) to remain in a non-replicating, antibiotic-tolerant state characterized by metabolic remodeling, including induction of the Rel _Mtb -mediated stringent response. We developed a novel therapeutic DNA vaccine construct involving fusion of the rel _Mtb gene with the immature dendritic cell-targeting gene encoding chemokine MIP-3α/CCL20. To augment mucosal immune responses, intranasal delivery was also evaluated. We found that the intramuscular MIP-3α / rel _Mtb (fusion) vaccine potentiates isoniazid activity more than a similar DNA vaccine expressing rel _Mtb alone in a chronic TB mouse model (absolute reduction of Mtb burden: 0.63 log ₁₀ colony-forming units, P=0.0001), inducing pronounced Mtb -protective immune signatures. The intranasal fusion vaccine, an approach combining rel _Mtb fusion to MIP-3α and intranasal delivery, demonstrated the greatest therapeutic effect compared to each approach alone, as evidenced by robust Th1 and Th17 responses systemically and locally and the greatest mycobactericidal activity when combined with isoniazid (absolute reduction of Mtb burden: 1.13 log ₁₀ , P<0.0001, when compared to the intramuscular vaccine targeting rel _Mtb alone). This DNA vaccination strategy may be a promising adjunctive approach combined with standard therapy to shorten curative TB treatment, and also serve as proof-of-concept for treating other chronic infections.