HIV Antiretroviral Therapy Research Articles

Loss to follow-up among people living with HIV on tuberculosis preventive treatment at four regional referral hospitals, Uganda, 2019–2021

IntroductionTuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV). TB preventive treatment (TPT) can prevent active TB infection in PLHIV for several years after it is completed. During 2019–2021, the six-month course of TPT (using isoniazid) was the most readily available in Uganda; however, program data indicated a TPT program loss to follow-up (LTFU) rate of 12 % during this period. We evaluated factors associated with TPT LTFU among PLHIV in four regional referral hospitals (RRHs) in Uganda from 2019 to 2021. MethodsWe abstracted program data from TPT registers on patient LTFU at Masaka, Mbale, Mubende, and Jinja RRHs. Additional data collected included client demographics, duration on HIV antiretroviral therapy (ART), year of TPT initiation, adherence, and point of entry. LTFU was defined as the failure to finish six consecutive months of isoniazid without stopping for more than two months at a time. We conducted bivariate analysis using the chi-square test for independence. Variables with p < 0.05 in bivariate analysis were included in a logistic regression model to establish independent factors associated with LTFU. ResultsOverall, 24,206 clients were started on TPT in the four RRHs. Their median age was 40 years (range, 1–90 years), and 15,962 (66 %) were female. A total of 22,260 (92 %) had TPT adherence >95 %. Independent factors associated with LTFU included being on ART for <3 months (AOR: 3.1, 95 % CI: 2.1–4.5) and 20–24 years (AOR: 4.7, 95 % CI: 1.9–12) or 25–29 years (AOR: 3.3, 95 % CI: 1.3–8.2) compared to 15–19 years. ConclusionsPLHIV just starting ART and young adults had higher odds of being LTFU from TPT during 2019–2021 in the four RRHs. Close follow-up of PLHIV aged 20–29 years and those newly initiated on ART could improve TPT completion.

Cohort profile: longitudinal and population comparison of children who are HIV-exposed uninfected and children who are HIV unexposed in Kenya (HOPE study)

PurposeGlobally, the number of children/adolescents exposed to HIV but uninfected (HIV-exposed uninfected, HEU) is growing. The HEU outcomes: population-evaluation and screening strategies study was designed to provide population-level evidence of...

COVID-19 Vaccines and COVID-19 in People Living with HIV.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly around the world, and COVID-19 and HIV co-infection also became common. In this study, we aimed to investigate the impact of vaccination preferences and vaccination rates on the severity of COVID-19 in patients with HIV co-infection. People living with HIV who were followed in our hospital during the COVID-19 pandemic (January 2020- December 2022) were retrospectively included in the study. The diagnosis of COVID-19 was made by detecting SARS-CoV-2 RNA in nasopharyngeal swab specimens using real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). Patients requiring hospital admission were classified as severe. The patient's demographics and vaccination status were collected from the hospital data system. Our study included 205 patients using antiretroviral therapy for HIV. The mean day count between the last vaccine date and SARS-CoV-2 PCR positivity was 163 days in the Comirnaty® group,149 days in the CoronaVac® group, and 154 days in the mixed-vaccinated group. Those vaccinated with Comirnaty® were statistically significantly less infected with COVID-19 after vaccination (p<0.05). The course and the outcomes of COVID-19 among SARS-CoV-2 vaccinated people living with HIV, especially with well-controlled HIV infection, seem to be similar to people living without HIV.

Gestational weight gain and adverse birth outcomes in South African women with HIV on antiretroviral therapy and without HIV: a prospective cohort study.

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. 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. Among 292 participants (48% WHIV), median age was 29 years (IQR, 25-33), median pre-pregnancy body mass index (BMI) was 31 kg/m2 (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). 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.

Status-neutral community-based multilevel intervention to address intersectional stigma and discrimination, and increase HIV testing, PrEP, and ART uptake among YGBMSM in Ghanaian Slums: A clustered randomized control trial protocol.

While GBMSM constitute less than 2% of Ghana's population, their HIV prevalence surpasses the national average by more than eightfold, emphasizing the critical need for targeted interventions to improve detection, care linkage, and reduce community transmission. This study seeks to increase HIV testing, Pre-Exposure Prophylaxis (PrEP), and Antiretroviral Therapy (ART) uptake (HPART) among YGBMSM through the adaptation of an evidence-based intervention (LAFIYA). We will employ the ADAPTT-IT framework to adapt LAFIYA and evaluate its feasibility and effectiveness in addressing intersectional stigma and increasing HPART uptake among YGBMSM residing in Ghanaian slums. In aim 1, we will hold focus groups (n=5) and interviews (n=20) among YGBMSM and two FGDs among GBMSM-led organizations. At the HCF level, we will hold 6 FGDs and interviews (n=20) among nurses. In AIM 2, we will randomly assign 6 healthcare facilities (HCFs) to receive the LAFIYA (n=3) or wait-list control (n=3). Friend groups (cluster) of YGBMSM (N=240) will be assigned to receive LAFIYA (n=120) or a wait-list control (n=120). We will collect 3-, 6-, and 9-months post-intervention data among YGBMSM(n=240) and HCWs(n=300) to measure HPART adherence (primary outcomes), ISD reduction, HIV and status-neutral knowledge (secondary outcomes), and intervention acceptability, appropriateness, and feasibility (implementation outcomes). The intervention group will observe increased HPART adherence, reduced ISD, and enhanced HPART knowledge and efficacy relative to the wait-list control group. The findings will inform ISD reduction and HIV status-neutral implementation strategies - and place-based interventions that address access to HIV prevention and care among YGBMSM, slum and in different settings. This study was registered on clinicalTrail.gov, with identifier number NCT06312514 on 03/14/2023. https://classic.clinicaltrials.gov/ct2/show/NCT06312514.

Accelerated Aging process in Patients Living with HIV: Role of Mitochondrial Dysfunction.

Introduction Despite the success of antiretroviral therapy (ART) in making HIV a chronic condition, People living with HIV (PLWH) experience an increased prevalence of age-related diseases earlier than HIV-negative individuals. These conditions span cardiovascular, metabolic, and neurologic illnesses, suggesting an advanced aging process influenced by chronic inflammation, known as “Inflammaging.” HIV-associated-mitochondrial dysfunction (HIVAMD) is proposed as a significant factor driving this accelerated aging, linked to chronic low-grade inflammation, immune activation, and the side effects of ART. Methods The review delves into the mechanics of mitochondrial dysfunction, highlighting how HIV infection and ART disrupt mitochondrial bioenergetics, leading to oxidative stress and cellular damage. Additionally, the document explores the roles of HIV proteins and ART in exacerbating mitochondrial dysfunction, alongside the effects of CD38 overactivation and IDO-1 pathways, which further deplete NAD+ levels and impair cellular metabolism. Results The analysis underscores the pivotal role of mitochondrial dysfunction in driving accelerated aging in PLWH, highlighting its association with chronic inflammation, immune dysregulation, and ART-related effects. By elucidating the mechanisms underlying HIVAMD, the review emphasizes the importance of targeting mitochondrial dysfunction and associated metabolic pathways as therapeutic strategies to mitigate accelerated aging in PLWH. Conclusion The review advocates for future research endeavors aimed at exploring interventions that could reverse or ameliorate HIVAMD, employing a geroscience-guided approach to enhance the healthspan and quality of life for PLWH. It underscores the need for comprehensive strategies combining pharmacological and non-pharmacological interventions to address the complex interplay between HIV, its treatment, and aging processes.

Connection Between HIV and Mitochondria in Cardiovascular Disease and Implications for Treatments.

HIV infection and antiretroviral therapy alter mitochondrial function, which can progressively lead to mitochondrial damage and accelerated aging. The interaction between persistent HIV reservoirs and mitochondria may provide insight into the relatively high rates of cardiovascular disease and mortality in persons living with HIV. In this review, we explore the intricate relationship between HIV and mitochondrial function, highlighting the potential for novel therapeutic strategies in the context of cardiovascular diseases. We reflect on mitochondrial dynamics, mitochondrial DNA, and mitochondrial antiviral signaling protein in the context of HIV. Furthermore, we summarize how toxicities related to early antiretroviral therapy and current highly active antiretroviral therapy can contribute to mitochondrial dysregulation, chronic inflammation, and poor clinical outcomes. There is a need to understand the mechanisms and develop new targeted therapies. We further consider current and potential future therapies for HIV and their interplay with mitochondria. We reflect on the next-generation antiretroviral therapies and HIV cure due to the direct and indirect effects of HIV persistence, associated comorbidities, coinfections, and the advancement of interdisciplinary research fields. This includes exploring novel and creative approaches to target mitochondria for therapeutic intervention.

HIV infection and ART exposure affect tumor TCR repertoire of diffuse large B cell lymphoma.

The most common subtype of lymphoma globally, diffuse large B cell lymphoma (DLBCL), is a leading cause of cancer death in people with HIV. The restructuring of the T cell compartment because of HIV infection and antiretroviral therapy (ART) may have implications for modern treatment selection, but current understanding of these dynamic interactions is limited. Here, we investigated the T cell response to DLBCL by sequencing the T cell receptor (TCR) repertoire in a cohort of HIV-negative (HIV-), HIV+/ART-experienced, and HIV+/ART-naive patients with DLBCL. HIV+/ART-naive tumor TCR repertoires were more clonal and more distinct from each other than HIV- and HIV+/ART-experienced ones. Further, increased overlap between tumor and blood TCR repertoires was associated with improved survival and HIV/ART status. Our study describes TCR repertoire characteristics for the first time to our knowledge in an African DLBCL cohort and demonstrates contributions of HIV infection and ART exposure to the DLBCL TCR repertoire.

Enhanced cervical cancer and HIV interventions reduce the disproportionate burden of cervical cancer cases among women living with HIV: A modeling analysis.

Women living with HIV experience heightened risk of cervical cancer, and over 50% of cases in Southern Africa are attributed to HIV co-infection. Cervical cancer interventions tailored by HIV status delivered with HIV antiretroviral therapy (ART) for treatment can decrease cancer incidence, but impact on HIV-related disparities remains understudied. Using a dynamic model calibrated to KwaZulu-Natal, South Africa, we projected HIV prevalence, cervical cancer incidence, and proportion of cancer cases among women living with HIV between 2021-2071. Relative to the status quo of moderate intervention coverage, we modeled three additive scenarios: 1) ART scale-up only; 2) expanded human papillomavirus (HPV) vaccination, screening, and treatment; and 3) catch-up HPV vaccination and enhanced screening for women living with HIV. Under the status quo, HIV prevalence among women aged 15+ decreased from a median of 35% [Uncertainty Range (UR): 26-42%] in 2021 to 25% [19-34%] in 2071. The proportion of cervical cancer cases that were women living with HIV declined from 73% [63-86%] to 58% [47-74%], but incidence remained 4.3-fold [3.3-5.7] that of women without HIV. ART scale-up reduced HIV prevalence in 2071, but increased the incidence rate ratio to 5.2 [3.7-7.3]. Disparities remained after expanding cancer interventions for all women (incidence rate ratio: 4.8 [3.6-7.6]), while additional catch-up HPV vaccination and screening for women living with HIV decreased the incidence rate ratio to 2.7 [1.9-3.4] in 2071. Tailored cervical cancer interventions for women living with HIV can counteract rising cancer incidence incurred by extended life expectancy on ART and reduce disparate cancer burden.

Prevalence of HIV-related stigma manifestations and their contributing factors among people living with HIV in Sweden – a nationwide study

BackgroundWith access to antiretroviral therapy (ART) HIV infection is a chronic manageable condition and non-sexually transmissible. Yet, many people living with HIV still testify about experiencing HIV-related stigma and discrimination. It is well-documented that HIV-related stigma and discrimination continue to be critical barriers to prevention, treatment, care and quality of life. From an individual stigma-reduction intervention perspective, it is essential to identify individual and interpersonal factors associated with HIV-related stigma manifestations. To address this issue and to expand the literature, the aim of this study was to assess the prevalence of HIV-related stigma manifestations and their associated factors among a diverse sample of people living with HIV in Sweden.MethodData from 1 096 participants were derived from a nationally representative, anonymous cross-sectional survey ”Living with HIV in Sweden”. HIV-related stigma manifestations were assessed using the validated Swedish 12-item HIV Stigma Scale encompassing four HIV-related stigma manifestations: personalised stigma, concerns with public attitudes towards people living with HIV, concerns with sharing HIV status, and internalized stigma. Variables potentially associated with the HIV-related stigma manifestations were divided into four categories: demographic characteristics, clinical HIV factors, distress and ART adherence, and available emotional HIV-related support. Four multivariable hierarchical linear regression analyses were employed to explore the associations between multiple contributors and HIV-related stigma manifestations.ResultsThe most dominating stigma feature was anticipation of HIV-related stigma. It was manifested in high scores on concerns with sharing HIV status reported by 78% of the participants and high scores on concerns about public attitudes towards people living with HIV reported by 54% of the participants. High scores on personalised stigma and internalized stigma were reported by around one third of the participants respectively. Between 23 and 31% of the variance of the four reported HIV-related stigma manifestations were explained mainly by the same pattern of associated factors including female gender, shorter time since HIV diagnosis, feelings of hopelessness, non-sharing HIV status, and lack of available emotional HIV-related support.ConclusionThe most dominating stigma feature was anticipation of stigma. Female gender, shorter time since HIV diagnosis, feelings of hopelessness, non-sharing HIV status, and lack of available emotional HIV-related support constituted potential vulnerability factors of the four HIV-related stigma manifestations. Our findings highlight the vital necessity to support people living with HIV to increase their resilience to stigma in its different forms. Exploring associated factors of HIV-related stigma manifestations may give an indication of what circumstances may increase the risk of stigma burden and factors amenable to targeted interventions. As individual stigma-reductions interventions cannot be performed isolated from HIV-related stigma and discrimination in society, a key challenge is to intensify anti-stigma interventions also on the societal level.

Vision Problems As a Contributor to Lower Engagement in Care Among Aging Men Living with HIV

ABSTRACT Purpose To investigate vision impairment as a barrier to engagement in medical care among aging persons living with HIV (PLWH) who experience multimorbidity and complex care needs. Setting Multicenter AIDS Cohort Study (MACS), a prospective observational cohort of aging PLWH men. Methods We examined relationships of self-reported vision difficulty with indicators of care engagement: 1) adherence to HIV antiretroviral therapy (ART; defined as taking ≥95% of medications); 2) self-reported avoidance of medical care; 3) self-reported tendency to ask a doctor questions about care (>2 questions at a medical visit), as well as with quality of life. A modified version of the National Eye Institute Vision Function Questionnaire was administered at three semi-annual visits (from October 2017 to March 2019) to assess difficulty performing vision-dependent tasks. Results We included 1063 PLWH (median age 57 years, 31% Black). Data on care engagement outcomes were analyzed using repeated measures logistic regression with generalized estimating equations adjusted for race, and at visit values for age, education level, depressive symptoms, alcohol use, and smoking status. Compared to no vision difficulty, those reporting moderate to extreme vision difficulty on at least one task had 2.2 times higher odds (95% CI: 1.4, 3.4) of having less than optimal ART adherence, 1.9 times higher odds (95% CI: 1.1, 3.4) of avoiding necessary medical care and median quality of life scores 8 points lower. Conclusion These findings suggest vision impairment decreases medical care engagement including HIV care and quality of life among aging PLWH.

Correlation of Oral Microbiota With Different Immune Responses to Antiretroviral Therapy in People Living With HIV

Abstract Both HIV infection and antiretroviral therapy (ART) affect the oral microbiome. Whether successful treatment with ART in people living with HIV (PLWH), which leads to a significant decline in viral loads and immune reconstitution, is associated with changes in or recovery of the oral microbiome remains unknown. Therefore, we performed a cross-sectional study of 118 PLWH receiving regular ART and 40 healthy controls (HCs). Among the 118 PLWH, 18 immunological nonresponders (INRs; &lt;200 CD4+ T cells/μL) and 30 immunological responders (IRs; ≥500 CD4+ T cells/μL) were identified. The oral microbiota composition of all participants was analyzed using 16S rRNA gene sequencing of throat swab samples. Relative abundance of bacterial genera was compared between IRs and INRs, and Pearson correlations between bacterial abundance and peripheral blood immune cell counts were evaluated. The INR group showed lower alpha diversity than the IR and HC groups, which displayed similar alpha diversity. The genera Alloprevotella, Prevotella and Neisseria were more abundant in PLWH than in HCs, whereas the genera Rothia, Streptococcus and Fusobacterium were more abundant in HCs than in PLWH. The genus Rothia was more abundant in the INR group, whereas Prevotella, Alloprevotella, Porphyromonas and Haemophilus were more abundant in the IR group. The genera Rothia and Alloprevotella were negatively and positively associated with CD4+ T cell counts, respectively. Thus, an increased abundance of Rothia in the oral microbiome is associated with unfavorable outcomes regarding immune reconstitution in PLWH receiving regular ART, whereas Prevotella, Alloprevotella, Porphyromonas and Haemophilus are associated with favorable outcomes.

Analysis of the immunological response to antiviral therapy in patients with different subtypes of HIV/AIDS: a retrospective cohort study

ObjectiveTo evaluate the effectiveness of standardised antiretroviral therapy (ART) among different HIV subtypes in people living with HIV/AIDS (PLWHA), and to screen the best ART regimen for this patient population.DesignA...

Mitochondrial DNA and Electron Transport Chain Protein Levels Are Altered in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy: A Pilot Study.

Distal sensory polyneuropathy (DSP) and distal neuropathic pain (DNP) remain significant challenges for older people with HIV (PWH), necessitating enhanced clinical attention. HIV and certain antiretroviral therapies (ARTs) can compromise mitochondrial function and impact mitochondrial DNA (mtDNA) replication, which is linked to DSP in ART-treated PWH. This study investigated mtDNA, mitochondrial fission and fusion proteins, and mitochondrial electron transport chain protein changes in the dorsal root ganglions (DRGs) and sural nerves (SuNs) of 11 autopsied PWH. In antemortem standardized assessments, six had no or one sign of DSP, while five exhibited two or more DSP signs. Digital droplet polymerase chain reaction was used to measure mtDNA quantity and the common deletions in isolated DNA. We found lower mtDNA copy numbers in DSP+ donors. SuNs exhibited a higher proportion of mtDNA common deletion than DRGs in both groups. Mitochondrial electron transport chain (ETC) proteins were altered in the DRGs of DSP+ compared to DSP- donors, particularly Complex I. These findings suggest that reduced mtDNA quantity and increased common deletion abundance may contribute to DSP in PWH, indicating diminished mitochondrial activity in the sensory neurons. Accumulated ETC proteins in the DRG imply impaired mitochondrial transport to the sensory neuron's distal portion. Identifying molecules to safeguard mitochondrial integrity could aid in treating or preventing HIV-associated peripheral neuropathy.

Trends in body mass index in the pre-dolutegravir period in South Africa.

Antiretroviral therapy (ART) is associated with weight gain, but this has been shown to be more marked with dolutegravir and other integrase strand transfer inhibitors. We studied weight gain in people living with HIV (PLWH) on ART compared to the general population in the period before dolutegravir was introduced in a rural South African cohort. Longitudinal analysis of the Ndlovu Cohort Study including 36-48 months' follow-up data. From 2014 to 2019, data were collected annually in Limpopo, rural South Africa. Linear mixed models using HIV status, demographics, ART use and cardiovascular risk factors were used to estimate trends in body mass index (BMI) over time. In total, 1518 adult, non-pregnant participants were included, of whom 518 were PLWH on ART (79.8%), 135 PLWH not yet on ART (20.2%) and 865 HIV-negative. HIV-negative participants had significantly higher BMIs than PLWH on ART at all study visits. There was a significant increase in BMI in all subgroups after 36 months (PLWH on ART, BMI +1.2 kg/m2, P < 0.001; PLWH not on ART, BMI +1.8 kg/m2, P < 0.001 and HIV-negative, BMI +1.3 kg/m2, P < 0.001). The increase in BMI in PLWH and HIV-negative participants is a serious warning signal as obesity results in morbidity and mortality.

Heavy alcohol use and the HIV care continuum in Kenya: a population-based study

ABSTRACT Heavy alcohol use (HAU) can destabilize engagement along the HIV care continuum. Population-based studies assessing associations of HAU with HIV treatment outcomes are lacking, especially in sub-Saharan Africa. We leveraged data from the Kenya Population-based HIV Impact Assessment to identify associations of self-reported HAU, assessed using two items measuring the frequency and quantity of past-year alcohol consumption, with serum biomarkers for HIV serostatus unawareness, antiretroviral therapy (ART) non-use, and HIV viremia (≥1000 RNA copies/mL). Overall and sex-stratified survey-weighted logistic regression with jackknife variance estimation modeled adjusted odds ratios (adjOR) of HIV treatment indicators by HAU. Overall, 1491 persons living with HIV aged 15–64 years (68.4% female) were included. The prevalence of HAU was 8.9% (95% confidence interval [95%CI]: 6.8–11.0%) and was significantly more pronounced in males than females (19.6% vs. 4.0%, p < 0.001). In multivariable analysis, HAU was significantly (p < 0.001) associated with HIV serostatus unawareness (adjOR = 3.65, 95%CI: 2.14–6.23), ART non-use (adjOR = 3.81, 95%CI: 2.25–6.43), and HIV viremia (adjOR = 3.13, 95%CI: 1.85–5.32). Incorporating sex-specific alcohol use screening into HIV testing and treatment services in populations where HAU is prevalent could optimize clinical outcomes along the HIV care continuum.

The Social Construction of Aging Among a Clinic-Based Population and Their Healthcare Workers in Zambia.

We sought to understand the social construction of aging in a clinic-based population, with and without HIV, to address gaps in care for older individuals living with HIV in Zambia. Our exploratory qualitative study included 36 in-depth interviews with clinic clients and four focus group discussions with 36 professional and lay healthcare workers providing services to the clients. We identified themes based on social construction theory. At the individual level, aging was multidimensional, perceived both as an achievement in the HIV era and as a period of cognitive, physical, and economic decline. In social interactions, older individuals were often stereotyped and treated as helpless, poor, and "witches." Those living with HIV faced the additional stigma of being labeled as promiscuous. Some of the participants living without HIV refused to take daily medication for non-communicable diseases to avoid being mistaken for taking antiretroviral therapy for HIV. Older individuals wanted quality healthcare and family support to address the intersectional stigma of aging, poverty, and chronic illness. Multifaceted interventions are required to combat age-related prejudice, intersectional stigma, and discriminatory practices, particularly for people living with HIV.

Can routine antenatal data be used to assess HIV antiretroviral therapy coverage among pregnant women? Evaluating the validity of different data sources in the Western Cape, South Africa.

Accurate measurement of antenatal antiretroviral treatment (ART) coverage in pregnancy is imperative in tracking progress towards elimination of vertical HIV transmission. In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources, enabling the description of temporal changes in population-wide antenatal antiretroviral coverage. We evaluated the validity of different methods for measuring ART coverage among pregnant women. We compared self-reported ART data from a 2014 antenatal survey with laboratory assay data from a sub-sample within the survey population. Thereafter, we conducted a retrospective cohort analysis of all pregnancies consolidated in the Provincial Health Data Centre (PHDC) from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. ART coverage estimates were triangulated with available antenatal survey estimates, aggregated programmatic data from registers recorded in the District Health Information System (DHIS) and Thembisa modelling estimates. Self-reported ART in the 2014 sentinel antenatal survey (n = 1434) had high sensitivity (83.5%), specificity (94.5%) and agreement (k = 0.8) with the gold standard of laboratory analysis of ART. Based on linked routine data, ART coverage by the time of delivery in mothers of live births increased from 67.4% in 2011 to 94.7% by 2019. This pattern of increasing antenatal ART coverage was also seen in the DHIS data, and estimated by the Thembisa model, but was less consistent in the antenatal survey data. This study is the first in a high-burden HIV setting to compare sentinel ART surveillance data with consolidated individuated administrative data. Although self-report in survey conditions showed high validity, more recent data sources based on self-report and medical records may be uncertain with increasing ART coverage over time. Linked individuated data may offer a promising option for ART coverage estimation with greater granularity and efficiency.

The impact of non-disclosure of HIV status and antiretroviral therapy on HIV recency testing and incidence algorithms.

Accurate HIV incidence estimates among blood donors are necessary to assess the effectiveness of programs aimed at limiting transfusion-transmitted HIV. We assessed the impact of undisclosed HIV status and antiretroviral (ARV) use on HIV recency and incidence estimates using increasingly comprehensive recent infection testing algorithms. Using 2017 donation data from first-time and lapsed donors, we populated four HIV recency algorithms: (1) serology and limiting-antigen avidity testing, (2) with individual donation nucleic amplification testing (ID-NAT) added to Algorithm 1, (3) with viral load added to Algorithm 2 and (4) with ARV testing added to Algorithm 3. Algorithm-specific mean durations of recent infection (MDRI) and false recency rates (FRR) were calculated and used to derive and compare incidence estimates. Compared with Algorithm 4, progressive algorithms misclassified fewer donors as recent: Algorithm 1: 61 (12.1%); Algorithm 2: 14 (2.8%) and Algorithm 3: 3 (0.6%). Algorithm-specific MDRI and FRR values resulted in marginally lower incidence estimates: Algorithm 1: 0.19% per annum (p.a.) (95% confidence interval [CI]: 0.13%-0.26%); Algorithm 2: 0.18% p.a. (95% CI: 0.13%-0.22%); Algorithm 3: 0.17% p.a. (95% CI: 0.13%-0.22%) and Algorithm 4: 0.17% p.a. (95% CI: 0.13%-0.21%). We confirmed significant misclassification of recent HIV cases when not including viral load and ARV testing. Context-specific MDRI and FRR resulted in progressively lower incidence estimates but did not fully account for the context-specific variability in incidence modelling. The inclusion of ARV testing, in addition to viral load and ID-NAT testing, did not have a significant impact on incidence estimates.

Bictegravir/emtricitabine/tenofovir alafenamide as first-line treatment in naïve HIV patients in a rapid-initiation model of care: BIC-NOW clinical trial

ObjectiveMultiple strategies have been utilised to reduce the incidence of HIV, including PrEP and rapid antiretroviral therapy initiation. The study objectives were to evaluate the efficacy, safety, satisfaction, treatment adherence, and system retention obtained with rapid initiation of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in naïve patients. MethodsThis phase IV, multicenter, open-label, single-arm, 48-week clinical trial enrolled patients between January 2020 and June 2022. Adherence to treatment was evaluated with the SMAQ questionnaire and patient satisfaction with the EQ-5D. ResultsTwo hundred eight participants were enrolled with mean age of 35.6 years; 87.6% were males; mean CD4 count was 393.5 cells/uL (<200 cells/uL in 22.1%); viral load log was 5.6 (VL>100 000 cop/mL in 43.3%); 22.6% had AIDS, and 4.3% were coinfected with HBV. BIC/FTC/TAF was initiated on the day of their first visit to the HIV specialist in 98.6% of participants, and 9.6% were lost to follow-up. The efficacy at week 48 was 84.1 % by intention-to- treat (ITT), 94.6% by modified ITT, and 98.3% by per protocol analysis. The regimen was discontinued in two subjects (0.9%) during week 1 for grade 3 adverse events. Treatment adherence (weeks 4 [90%, IQR: 80–99%] vs. 48 [90%, IQR: 80–95%; P = 0.49]) and patient satisfaction (weeks 4 [90%, IQR: 80–99%] vs. 48 [90%, IQR: 80–95 P = 0.49]) rates were very high over the 48- week study period. ConclusionsBIC/FTC/TAF is an appropriate option for rapid ART initiation in naïve HIV patients, offering high efficacy, safety, durability, treatment adherence, retention in the healthcare system, and patient satisfaction. Number Clinical Trial registration: NCT06177574.