Current HIV Research - Volume 18, Issue 1, 2020

Background: People living with HIV (PLWHIV) have a 2-fold higher risk of having a cardiovascular event than HIV-negative individuals. Objective: The objective of this article is to estimate the pooled proportion of moderate-high cardiovascular risk in PLWHIV obtained through different scores. In addition, this study also aims to establish the prevalence of dyslipidemia, smoking habits, diabetes and high blood pressure in the included studies. Methods: A bibliographic search was conducted in MEDLINE for studies on cardiovascular risk assessment in PLWHVI that took place during the period of inception to July 2018. The eligibility criteria for inclusion were: cross-sectional or longitudinal studies on HIV-positive adults in which the prevalence of moderate-high cardiovascular risk (or data to calculate it) was reported, and included at least one of the following cardiovascular risk scores: Framingham, ASCVD, D:A:D, Progetto Cuore, PROCAM, SCORE, Regicor, and World Health Organization scores. Results: Bibliographic search identified 278 studies. Finally, thirty-nine peer-reviewed publications were identified for a collective total of 13698 subjects. The pooled prevalence of moderate-high cardiovascular risk in PLWHIV obtained with nine different scores through random-effect modeling was 20.41% (95% CI: 16.77-24.31). The most prevalent concomitant cardiovascular risk factor was dyslipidemia (39.5%), smoking (33.0 %), high blood pressure (19.8%) and diabetes (7.24%). Conclusion: Data obtained in this systematic review indicate that more than 1 in every five subjects with HIV have a moderate-high cardiovascular risk. In consequence, the burden of cardiovascular disease in PLWHIV represents a public health problem. There is an urgent need to develop strategies to prevent and detect cardiovascular risk effectively in PLWHIV.

The main advantage of animal models of infectious diseases over in vitro studies is the gain in the understanding of the complex dynamics between the immune system and the pathogen. While small animal models have practical advantages over large animal models, it is crucial to be aware of their limitations. Although the small animal model at least needs to be susceptible to the pathogen under study to obtain meaningful data, key elements of pathogenesis should also be reflected when compared to humans. Well-designed small animal models for HIV, hepatitis viruses and tuberculosis require, additionally, a thorough understanding of the similarities and differences in the immune responses between humans and small animals and should incorporate that knowledge into the goals of the study. To discuss these considerations, the NIAID hosted a workshop on ‘Small Animal Models for HIV, Hepatitis B, and Tuberculosis’ on May 30, 2019. Highlights of the workshop are outlined below.

Background: Despite the existence of evidence-based HIV-exposed infant feeding guidelines, infants in Africa still acquire HIV through inappropriate feeding practices. Objective: To identify predictors of HIV-exposed infant feeding knowledge and counseling practice among health care workers (HCW) in Nigeria. Methods: Structured, pretested questionnaires were administered to HCW (n=262) in a tertiary health facility in Kano, Nigeria. Multivariate logistic regression was used to determine predictors of HIV-exposed infant feeding knowledge and counseling practice. Results: Of 262 respondents, (58.0%, n=152) had good knowledge of recommended feeding options. Respondents listed exclusive breastfeeding (57.6%, n=151), human milk substitutes (45.4%, n=119), HIV-negative wet-nursing (37.0%, n=97), heated expressed human milk (20.6%, n=54) and mixed feeding (13.4%, n=35) as appropriate feeding choices. Over half (57.3%, n=150) of the respondents have ever counseled a HIV-positive mother on infant feeding. Knowledge was predicted by female sex (Adjusted Odds Ratio (AOR)=2.47, 95% Confidence Interval (CI):1.35-4.52), profession (physician vs. laboratory scientist, AOR=4.00, 95%CI:1.25-12.87; nurse/midwife vs. laboratory scientist, AOR=2.75, 95%CI:1.17-9.28), infant feeding counseling training (AOR=3.27, 95%CI:1.87-5.71), and number of children (2-4 vs. 0, AOR=1.75, 95%CI:1.23-3.92). Infant feeding counseling was predicted by female sex (AOR=2.85, 95%CI:1.39-5.85), age (>40 vs. <30 years, AOR=3.87, 95%CI:1.27-15.65), knowledge of infant feeding options (good vs. fair/poor, AOR=3.96, 95%CI:2.07-7.59), training (AOR=2.60, 95%CI:1.42-5.32), and profession (physician vs. laboratory scientist, AOR=10.7, 95%CI:2.85-40.54; nurse/midwife vs. laboratory scientist, AOR=4.8, 95%CI:1.26-18.02). Conclusion: The practice of infant feeding counseling among HCW in Nigeria is associated with sex, knowledge, and profession. Our findings may inform the development of targeted training programs for HCW in similar settings.

Background: The emergence of drug-resistant viral strains has created the need for the development of novel anti-HIV agents with a diverse structure that targets key enzymes in the HIV lifecycle. Objective: Considering the pharmacophore of integrase inhibitors, one of the validated targets for anti-HIV therapy, we designed a quinazolinone incorporated coumarin scaffold to affect HIV. Methods: Coumarin is a beta enol ester and also a well-known drug scaffold. Designed structures were prepared using a one-pot three-component reaction from 3-amino-4-hydroxycoumarin, isatoic anhydride and benzaldehyde derivatives. Results: In vitro anti-HIV and cytotoxicity assay indicated that more than half of the compounds had EC50 values lower than 50 μM. Unsubstituted phenyl derivative showed the highest activity and selectivity with an EC50 value of 5 μM and a therapeutic index of 7. Compounds were docked into the integrase active site to investigate the probable mechanism of action. Accordingly, the hydroxyl moiety of coumarin along with the carbonyl of the quinazolinone ring could function as the metal chelating group. Quinazolinone and phenyl groups interact with side chains of IN residues, as well. Conclusion: Here, a novel anti-HIV scaffold is represented for further modification and in-vivo studies.

Background: Antiretroviral therapy (ART), especially with tenofovir disoproxil fumarate (TDF), has been associated with accelerated bone turnover and leads to significant bone loss. Objective: We aimed to determine the effect of vitamin D2 and calcium on bone mineral density (BMD) in HIV-infected patients receiving TDF/emtricitabine (FTC)/efavirenz (EFV). Methods: A prospective, open-label, randomized controlled study was conducted. Eligible patients were ART naïve HIV individuals who initiated TDF/FTC/EFV. The study group received supplementation with vitamin D2 and calcium carbonate, whereas the control group was administered only ART. The primary outcome was the percentage change in total hip BMD at week 24 compared with baseline. Results: A total of 18 patients were randomized (9 in each group). The mean (standard deviation; SD) total hip BMD significantly decreased from baseline in both groups, from 0.96 (0.14) g/cm2 to 0.93 (0.13) g/cm2 in the study group (p = 0.006) and from 0.87 (0.11) g/cm2 to 0.84 (0.11) g/cm2 in the control group (p = 0.004). The mean (SD) lumbar spine BMD significantly decreased from baseline in both groups, from 1.00 (0.13) g/cm2 to 0.97 (0.13) g/cm2 (p = 0.004) in the study group and from 0.90 (0.09) g/cm3 to 0.86 (0.08) g/cm2 in the control group (p = 0.006). At week 24, the mean (SD) lumbar spine BMD was significantly greater in the study group than in the control group (p = 0.042). However, there were no significant differences in the percentage change of total hip, lumbar spine, and femoral neck BMD between both groups. No adverse events were reported. In conclusion, as early as 24 weeks after TDF initiation, a significant decline in BMD was detected. Conclusion: Vitamin D2 and calcium supplements should be considered for HIV-infected patients receiving TDF/FTC/EFV in a resource-limited setting where there are limited ART options (Clinicaltrials. gov NCT0287643).

Background: In resource-rich settings, the rate of mother-to-child transmission of human immunodeficiency virus (HIV) has dramatically decreased by virtue of a combination of preventive strategies during the last two decades. Case Presentation: We present a case of progressive developmental milestone loss in a toddler with previously unknown congenitally acquired human immunodeficiency virus (HIV) infection, complicated by an Epstein-Barr virus (EBV) coinfection. Conclusion: Our report underscores the differential diagnosis between HIV encephalopathy and EBV encephalitis and the vertical transmission of the HIV infection, which constitutes an alarming issue in terms of public health.