-
Journal of the International AIDS... Jun 2024Outside of pregnancy, evidence shows that persons with HIV initiating or switching to dolutegravir (DTG)-based antiretroviral therapy (ART) experience greater weight...
INTRODUCTION
Outside of pregnancy, evidence shows that persons with HIV initiating or switching to dolutegravir (DTG)-based antiretroviral therapy (ART) experience greater weight gain compared to those on other ART classes. However, there are few data on the impact of DTG-based ART on gestational weight gain (GWG) in sub-Saharan Africa where HIV is most common. According to the National Academy of Medicine (NAM), GWG below and above NAM guidelines is associated with adverse birth outcomes. Therefore, the objective of this study was to describe GWG by HIV status and ART regimen, and examine the associations with adverse birth outcomes.
METHODS
We enrolled pregnant women with HIV (WHIV) and without HIV (≥18 years) in a peri-urban primary healthcare facility in Cape Town, South Africa between 2019 and 2022. GWG was study-measured at 24-28 (baseline) and 33-38 weeks gestation and converted to GWG rate (kg/week) in accordance with NAM guidelines. GWG z-scores were generated using the INTEGROWTH-21 and US standards to account for differing lengths of gestation. Birth outcome data were obtained from medical records. Associations of GWG z-score with adverse birth outcomes were assessed using multivariable linear or log-binomial regression.
RESULTS
Among 292 participants (48% WHIV), median age was 29 years (IQR, 25-33), median pre-pregnancy body mass index (BMI) was 31 kg/m (IQR, 26-36) and 20% were primiparous at baseline. The median weekly rate of GWG was 0.30 kg/week (IQR, 0.12-0.50), 35% had GWG below NAM standards (59% WHIV) and 48% had GWG above NAM standards (36% WHIV). WHIV gained weight more slowly (0.25 vs. 0.37 kg/week, p<0.01) than women without HIV. Weekly rate of GWG did not differ by ART regimen (DTG-based ART 0.25 vs. efavirenz-based ART 0.27 kg/week, p = 0.80). In multivariable analyses, GWG z-score was positively associated with continuous birth weight (mean difference = 68.53 95% CI 8.96, 128.10) and categorical high birth weight of >4000 g (RR = 2.18 95% CI 1.18, 4.01).
CONCLUSIONS
Despite slower GWG among WHIV, nearly half of all women gained weight faster than recommended by the NAM. GWG was positively associated with infant birth weight. Interventions to support healthy GWG in sub-Saharan Africa are urgently needed.
Topics: Humans; Female; Pregnancy; HIV Infections; Adult; South Africa; Prospective Studies; Gestational Weight Gain; Pregnancy Complications, Infectious; Young Adult; Pregnancy Outcome; Infant, Newborn; Pyridones; Oxazines; Anti-HIV Agents; Heterocyclic Compounds, 3-Ring; Piperazines
PubMed: 38926935
DOI: 10.1002/jia2.26313 -
European Journal of Medical Research Jun 2024The COVID-19 pandemic affected the self-management and care of people living with HIV, requiring adaptations in the way health services are provided. However, it is... (Review)
Review
Repercussions of the COVID-19 pandemic on the HIV care continuum and related factors in economically disadvantaged nations: an integrated analysis using mixed-methods systematic review.
BACKGROUND
The COVID-19 pandemic affected the self-management and care of people living with HIV, requiring adaptations in the way health services are provided. However, it is unclear how these changes impacted HIV care in low-income countries.
METHODS
A systematic review including the current evidence related to changes in HIV care continuum during COVID-19 was conducted through a systematic search in the online databases including CINAHL, OVID-Medline, CAB Direct, and OVID-Embase. A two-step screening process was carried out to include eligible papers and reports according to inclusion criteria.
RESULTS
From the searches we identified 21 total studies published between 2021 and 2024, the studies revealed mostly negative impacts on all stages of the HIV care continuum in low-income countries. There were impacts related to the blocking measures due to COVID-19, fear of contracting the disease, difficulties in providing resources such as income, food and transports, reductions in the provision of care from prevention to viral suppression.
CONCLUSION
Overall, researchers identified several negative impacts of COVID-19 restrictions on HIV care continuum during pandemic; however, some observations indicated indirect positive impacts on some aspects of HIV care. Decline in HIV care practices during pandemic compared to before pandemic were observed including using preventative methods, counseling and testing, receiving HIV healthcare services, HIV medical appointments, antiretroviral adherence, engagement with treatment, and poor viral suppression. However, in some evidence improvement in ART adherence and PrEP use were observed.
Topics: Humans; COVID-19; HIV Infections; Continuity of Patient Care; Developing Countries; Pandemics; SARS-CoV-2
PubMed: 38926792
DOI: 10.1186/s40001-024-01917-1 -
BMC Infectious Diseases Jun 2024Late human immunodeficiency virus (HIV) diagnosis is the most prominent cause of HIV/AIDS-related mortality and also increases the risk of transmission and spread of the...
BACKGROUND
Late human immunodeficiency virus (HIV) diagnosis is the most prominent cause of HIV/AIDS-related mortality and also increases the risk of transmission and spread of the disease in society. Adolescents are the most vulnerable population's age group for HIV infection in several settings, but expanding access to early HIV testing remains a challenge. Consequently, a significant proportion of adolescents are still dying of HIV-related causes, and the current study aimed at assessing the effect of late presentation on HIV-related mortality among adolescents living with HIV.
METHODS
An institutional-based retrospective cohort study was conducted from August 21-November 21, 2022, at selected public hospitals in the North Showa Zone of Oromiya, Ethiopia. All adolescents living with HIV who had received no ART and presented for ART follow-up at public hospitals from September 1, 2012, to August 31, 2021, were included in the study. Data entry was done by Epi-data version 3.1.1 software and exported to Stata version 16 for further analysis. Both bi-variable and multivariable analyses were performed using the Cox proportional hazard model to compare the HIV-related mortality of early and late-presented adolescents using an adjusted hazard ratio at a 95% confidence interval (CI).
RESULTS
A total of 341 medical records of adolescents were included in the study, contributing an overall incidence rate of 3.15 (95% CI: 2.21-4.26) deaths per 100 person-years of observation throughout the total follow-up period of 1173.98 person-years. Adolescents with late presentation for HIV care had three times the higher hazard of mortality (adjusted hazard ratio (aHR) = 3.00; 95% CI: 1.22-7.37) as compared to those with early presentation for HIV/AIDS care. Adolescents within the age range of 15-19 years old (aHR = 3.56; 95% CI: 1.44-8.77), rural residence (aHR = 2.81; 95% CI: 1.39-5.68), poor adherence to ART (aHR = 3.17; 95% CI: 1.49-6.76), and being anemic (aHR = 3.09; 95% CI: 1.52-6.29) were other independent predictors of HIV-related mortality.
CONCLUSION
The study found a substantial link between HIV late presentation to care and mortality among adolescents. Residence, age, antiretroviral therapy (ART) medication adherence, and anemia status were also found to be other independent predictors of HIV-related mortality. To achieve the ultimate aim of lowering mortality among adolescents living with HIV, rigorous emphasis must be placed on early presentation for HIV/AIDS care. In addition, counseling on adherence and prompt diagnosis and treatment of anemia are highly recommended to reduce mortality.
Topics: Humans; Ethiopia; Adolescent; Retrospective Studies; Male; HIV Infections; Female; Hospitals, Public; Young Adult; Delayed Diagnosis; Proportional Hazards Models
PubMed: 38926656
DOI: 10.1186/s12879-024-09550-3 -
The Lancet. HIV Jul 2024Approximately 200 000 South Africans acquired HIV in 2021 despite the availability of universal HIV test and treat and pre-exposure prophylaxis (PrEP). The aim of this... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of integrating HIV prevention within sexual reproductive health services with or without peer support among adolescents and young adults in rural KwaZulu-Natal, South Africa (Isisekelo Sempilo): 2 × 2 factorial, open-label, randomised controlled trial.
BACKGROUND
Approximately 200 000 South Africans acquired HIV in 2021 despite the availability of universal HIV test and treat and pre-exposure prophylaxis (PrEP). The aim of this study was to test the effectiveness of sexual and reproductive health services or peer support, or both, on the uptake of serostatus neutral HIV services or reduction of sexually transmissible HIV.
METHODS
We did an open-label, 2 × 2 randomised factorial trial among young people in a mostly rural area of KwaZulu-Natal, South Africa. Inclusion criteria included being aged 16-29 years, living in the mapped geographical areas that were accessible to the area-based peer navigators, being willing and able to provide informed consent, and being willing to provide a dried blood spot for anonymous HIV testing and HIV viral load measurement at 12 months. Participants were randomly allocated by computer-generated algorithm to one of four groups: those in the standard-of-care group were referred to youth-friendly services for differentiated HIV prevention (condoms, universal HIV test and treat with antiretroviral therapy, and PrEP if eligible); those in the sexual and reproductive health services group received baseline self-collected specimens for sexually transmitted infection (STI) testing and referral to integrated sexual and reproductive health and HIV prevention services; those in the peer support group were referred to peer navigators for health promotion, condom provision, and facilitation of attendance for differentiated HIV prevention services; and those in the final group received a combination of sexual and reproductive health services and peer support. Coprimary outcomes were linkage to clinical services within 60 days of enrolment, proportion of participants who had sexually transmissible HIV at 12 months after enrolment, and proportion of sampled individuals who consented to participation and gave a dried blood spot for HIV testing at 12 months. Logistic regression was used for analyses, and adjusted for age, sex, and rural or peri-urban area of residence. This study is registered with ClinicalTrials.gov (NCT04532307) and is closed.
FINDINGS
Between March 2, 2020, and July 7, 2022, 1743 (75·7%) of 2301 eligible individuals were enrolled and followed up. 12-month dried blood spots were collected from 1168 participants (67·0%). The median age of the participants was 21 years (IQR 18-25), 51·4% were female, and 51·1% had secondary level education. Baseline characteristics and 12-month outcome ascertainment were similar between groups. 755 (43·3%) linked to services by 60 days. 430 (49·8%) of 863 who were in the sexual reproductive health services group were linked to care compared with 325 (36·9%) of 880 who were not in the sexual and reproductive health services group (adjusted odds ratio [aOR] 1·68; 95% CI 1·39-2·04); peer support had no effect: 385 (43·5%) of 858 compared with 370 (43·1%) of 885 (1·02, 0·84-1·23). At 12 months, 227 (19%) tested ELISA-positive for HIV, of whom 41 (18%) had viral loads of 400 copies per mL; overall prevalence of transmissible HIV was 3·5%. 22 (3·7%) of 578 participants in the sexual and reproductive health services group had transmissible HIV compared with 19 (3·3%) of 590 not in the sexual and reproductive health services group (aOR 1·12; 95% CI 0·60-2·11). The findings were also non-significant for peer support: 21 (3·3%) of 565 compared with 20 (3·3%) of 603 (aOR 1·03; 95% CI 0·55-1·94). There were no serious adverse events or deaths during the study.
INTERPRETATION
This study provides evidence that STI testing and sexual and reproductive health services create demand for serostatus neutral HIV prevention in adolescents and young adults in Africa. STI testing and integration of HIV and sexual health has the potential to reach those at risk and tackle unmet sexual health needs.
FUNDING
US National Institute of Health, Bill & Melinda Gates Foundation, and 3ie.
Topics: Humans; Adolescent; HIV Infections; South Africa; Female; Young Adult; Male; Rural Population; Adult; Peer Group; Reproductive Health Services; HIV Testing; Pre-Exposure Prophylaxis; Viral Load
PubMed: 38925731
DOI: 10.1016/S2352-3018(24)00119-X -
Ageing Research Reviews Jun 2024The present perspective article proposes an etiopathological model for multiple sclerosis pathogenesis and progression associated with the activation of human endogenous... (Review)
Review
The present perspective article proposes an etiopathological model for multiple sclerosis pathogenesis and progression associated with the activation of human endogenous retroviruses. We reviewed preclinical, clinical, epidemiological, and evolutionary evidence indicating how the complex, multi-level interplay of genetic traits and environmental factors contributes to multiple sclerosis. We propose that endogenous retroviruses transactivation acts as a critical node in disease development. We also discuss the rationale for combined anti-retroviral therapy in multiple sclerosis as a disease-modifying therapeutic strategy. Finally, we propose that the immuno-pathogenic process triggered by endogenous retrovirus activation can be extended to aging and aging-related neurodegeneration. In this regard, endogenous retroviruses can be envisioned to act as epigenetic noise, favoring the proliferation of disorganized cellular subpopulations and accelerating system-specific "aging". Since inflammation and aging are two sides of the same coin (plastic dis-adaptation to external stimuli with system-specific degree of freedom), the two conditions may be epiphenomenal products of increased epigenomic entropy. Inflammation accelerates organ-specific aging, disrupting communication throughout critical systems of the body and producing symptoms. Overlapping neurological symptoms and syndromes may emerge from the activity of shared molecular networks that respond to endogenous retroviruses' reactivation.
PubMed: 38925481
DOI: 10.1016/j.arr.2024.102392 -
Antiviral Research Jun 2024Combinational antiretroviral therapy (cART) suppresses human immunodeficiency virus type 1 (HIV-1) viral replication and pathogenesis in acquired immunodeficiency...
Combinational antiretroviral therapy (cART) suppresses human immunodeficiency virus type 1 (HIV-1) viral replication and pathogenesis in acquired immunodeficiency syndrome (AIDS) patients. However, HIV-1 remains in the latent stage of infection by suppressing viral transcription, which hinders an HIV-1 cure. One approach for an HIV-1 cure is the "shock and kill" strategy. The strategy focuses on reactivating latent HIV-1, inducing the viral cytopathic effect and facilitating the immune clearance for the elimination of latent HIV-1 reservoirs. Here, we reported that the H3K4 trimethylation (H3K4me3)-specific demethylase KDM5A/B play a role in suppressing HIV-1 Tat/LTR-mediated viral transcription in HIV-1 latent cells. Furthermore, we evaluated the potential of KDM5-specific inhibitor JQKD82 as an HIV-1 "shock and kill" agent. Our results showed that JQKD82 increases the H3K4me3 level at HIV-1 5' LTR promoter regions, HIV-1 reactivation, and the cytopathic effects in an HIV-1-latent T cell model. In addition, we identified that the combination of JQKD82 and AZD5582, a non-canonical NF-κB activator, generates a synergistic impact on inducing HIV-1 lytic reactivation and cell death in the T cell. The latency-reversing potency of the JQKD82 and AZD5582 pair was also confirmed in peripheral blood mononuclear cells (PBMCs) isolated from HIV-1 aviremic patients and in an HIV-1 latent monocyte. In latently infected microglia (HC69) of the brain, either deletion or inhibition of KDM5A/B results in a reversal of the HIV-1 latency. Overall, we concluded that KDM5A/B function as a host repressor of the HIV-1 lytic reactivation and thus promote the latency and the survival of HIV-1 infected reservoirs.
PubMed: 38925368
DOI: 10.1016/j.antiviral.2024.105947 -
Journal of Clinical Virology : the... Jun 2024Human Immunodeficiency virus type 1 (HIV-1) remains a significant global health threat partly due to its ability to develop resistance to anti-retroviral therapies....
BACKGROUND
Human Immunodeficiency virus type 1 (HIV-1) remains a significant global health threat partly due to its ability to develop resistance to anti-retroviral therapies. HIV-1 genotype and drug resistance analysis of the polymerase (pol) sequence is a mainstay of its clinical and public health management. However, as new treatments and resistances evolve, analysis methods must change accordingly. In this study, we outline the development and implementation of a direct whole-genome sequencing approach (dWGS) using probe-capture target-enrichment for HIV-1 genotype and drug resistance analysis.
METHODS
We implemented dWGS and performed parallel pol Sanger sequencing for clinical samples, followed by comparative genotype and drug-resistance analysis. These HIV-1 WGS sequences were also utilised for a novel partitioned phylogenetic analysis.
RESULTS
Optimised nucleic acid extraction and DNAse I treatment significantly increased HIV-1 whole-genome coverage and depth, and improved recovery of high-quality genomes from low viral load clinical samples, enabling routine sequencing of viral loads as low as 1000 copies/mL. Overall, dWGS was robust, accurate and more sensitive for detecting low-frequency variants at drug-resistance sites compared to Sanger sequencing. Analysis of multiple sequence regions improved phylogenetic reconstruction for recombinant HIV-1 sequences compared to analysis of pol sequence alone.
CONCLUSIONS
These findings demonstrate dWGS enhances HIV-1 drug-resistance analysis by quantitative variant detection and improves reconstruction of HIV-1 phylogenies compared to traditional pol sequencing. This work supports that HIV-1 dWGS is a viable option to replace Sanger sequencing for clinical and public health applications.
PubMed: 38924832
DOI: 10.1016/j.jcv.2024.105709 -
Journal of the International AIDS... Jun 2024As access to effective antiretroviral therapy (ART) has improved globally, tobacco-related illnesses, including cardiovascular disease, cancer and chronic respiratory...
INTRODUCTION
As access to effective antiretroviral therapy (ART) has improved globally, tobacco-related illnesses, including cardiovascular disease, cancer and chronic respiratory conditions, account for a growing proportion of deaths among people with HIV (PWH). We estimated the impact of tobacco smoking and smoking cessation on life expectancy among PWH in South Africa.
METHODS
In a microsimulation model, we simulated 18 cohorts of PWH with virologic suppression, each homogenous by sex, initial age (35y/45y/55y) and smoking status (current/former/never). Input parameters were from data sources published between 2008 and 2022. We used South African data to estimate age-stratified mortality hazard ratios: 1.2-2.3 (females)/1.1-1.9 (males) for people with current versus never smoking status; and 1.0-1.3 (females)/1.0-1.5 (males) for people with former versus never smoking status, depending on age at cessation. We assumed smoking status remains unchanged during the simulation; people who formerly smoked quit at model start. Simulated PWH face a monthly probability of disengagement from care and virologic non-suppression. In sensitivity analysis, we varied smoking-associated and HIV-associated mortality risks. Additionally, we estimated the total life-years gained if a proportion of all virologically suppressed PWH stopped smoking.
RESULTS
Forty-five-year-old females/males with HIV with virologic suppression who smoke lose 5.3/3.7 life-years compared to PWH who never smoke. Smoking cessation at age 45y adds 3.4/2.4 life-years. Simulated PWH who continue smoking lose more life-years from smoking than from HIV (females, 5.3 vs. 3.0 life-years; males, 3.7 vs. 2.6 life-years). The impact of smoking and smoking cessation increase as smoking-associated mortality risks increase and HIV-associated mortality risks, including disengagement from care, decrease. Model results are most sensitive to the smoking-associated mortality hazard ratio; varying this parameter results in 1.0-5.1 life-years gained from cessation at age 45y. If 10-25% of virologically suppressed PWH aged 30-59y in South Africa stopped smoking now, 190,000-460,000 life-years would be gained.
CONCLUSIONS
Among virologically suppressed PWH in South Africa, tobacco smoking decreases life expectancy more than HIV. Integrating tobacco cessation interventions into HIV care, as endorsed by the World Health Organization, could substantially improve life expectancy.
Topics: Humans; Male; Life Expectancy; Female; HIV Infections; South Africa; Adult; Smoking Cessation; Middle Aged; Tobacco Smoking; Computer Simulation
PubMed: 38924347
DOI: 10.1002/jia2.26315 -
Journal of the International AIDS... Jun 2024Evidence-based intervention strategies to improve adherence among individuals living with chronic conditions are critical in ensuring better outcomes. In this systematic...
INTRODUCTION
Evidence-based intervention strategies to improve adherence among individuals living with chronic conditions are critical in ensuring better outcomes. In this systematic review, we assessed the impact of interventions that aimed to promote adherence to treatment for chronic conditions.
METHODS
We systematically searched PubMed, Web of Science, Scopus, Google Scholar and CINAHL databases to identify relevant studies published between the years 2000 and 2023 and used the QUIPS assessment tool to assess the quality and risk of bias of each study. We extracted data from eligible studies for study characteristics and description of interventions for the study populations of interest.
RESULTS
Of the 32,698 total studies/records screened, 2814 were eligible for abstract screening and of those, 497 were eligible for full-text screening. A total of 82 studies were subsequently included, describing a total of 58,043 patients. Of the total included studies, 58 (70.7%) were related to antiretroviral therapy for HIV, 6 (7.3%) were anti-hypertensive medication-related, 12 (14.6%) were anti-diabetic medication-related and 6 (7.3%) focused on medication for more than one condition. A total of 54/82 (65.9%) reported improved adherence based on the described study outcomes, 13/82 (15.9%) did not have clear results or defined outcomes, while 15/82 (18.3%) reported no significant difference between studied groups. The 82 publications described 98 unique interventions (some studies described more than one intervention). Among these intervention strategies, 13 (13.3%) were multifaceted (4/13 [30.8%] multi-component health services- and community-based programmes, 6/13 [46.2%] included individual plus group counselling and 3/13 [23.1%] included SMS or alarm reminders plus individual counselling).
DISCUSSION
The interventions described in this review ranged from adherence counselling to more complex interventions such as mobile health (mhealth) interventions. Combined interventions comprised of different components may be more effective than using a single component in isolation. However, the complexity involved in designing and implementing combined interventions often complicates the practicalities of such interventions.
CONCLUSIONS
There is substantial evidence that community- and home-based interventions, digital health interventions and adherence counselling interventions can improve adherence to medication for chronic conditions. Future research should answer if existing interventions can be used to develop less complicated multifaceted adherence intervention strategies.
Topics: Humans; Africa South of the Sahara; Chronic Disease; HIV Infections; Medication Adherence
PubMed: 38924296
DOI: 10.1002/jia2.26266 -
PloS One 2024Hepatitis B virus (HBV) constitutes a significant global health challenge, with more than 2 billion people infected globally and almost 291 million chronic cases. In...
Hepatitis B virus (HBV) constitutes a significant global health challenge, with more than 2 billion people infected globally and almost 291 million chronic cases. In Africa, coinfection of HBV with Human Immunodeficiency Virus (HIV) is high, yet the condition remains overlooked in many countries. While antiretroviral therapy (ART) has improved HIV survival, viral hepatitis continues to contribute to morbidity and mortality. Occult Hepatitis B infection (OBI), characterized by a low-level of HBV DNA in individuals with negative hepatitis B surface antigen (HBsAg), is an emerging concern among HIV seropositive individuals due to the risk of HBV reactivation and associated complications, especially hepatocellular carcinoma (HCC). Ghana has an estimated HBV/HIV coinfection prevalence of 13.6% making it important to also determine potential cases of OBI. This study aims to assess OBI prevalence in persons living with HIV (PLHIV). A cross-sectional study was conducted in five health facilities in the Cape Coast Metropolis. HBV-related serological markers were determined among 116 PLHIV using the Enzyme-Linked Immunosorbent Assay (ELISA) method. HBV DNA was extracted from 30 participants found to be HBsAg negative but positive for hepatitis B core antibody (HBcAb+). Nested PCR was employed in detecting HBV DNA and HBV viral load was performed using qPCR. The median age of the participants was 37 years (IQR 22-65). Serologically, 7.8% (n = 9, 95% CI: 3.5-22.7), 12.1% (n = 14), and 25.9% (n = 30) tested positive for solely HBsAg, HBsAb, and HBcAb respectively. OBI prevalence among HBsAg-/HBcAb+ participants was 16.7% (n = 5, 95% CI: 6.5-23.7) with a median HBV DNA level of 139.2 IU/ml (IQR, 96.7-142.0). The prevalence of OBI among HIV-positive participants in the Cape Coast Metropolis highlights the need to consider screening for HBV among HIV patients using nucleic acid amplification tests. This can inform medical management and reduce the risk of liver complications, including HCC.
Topics: Humans; Ghana; HIV Infections; Female; Male; Adult; Hepatitis B; Prevalence; Middle Aged; Cross-Sectional Studies; Hepatitis B virus; Hepatitis B Surface Antigens; Coinfection; DNA, Viral; Young Adult
PubMed: 38924017
DOI: 10.1371/journal.pone.0305862