Differences in adoption of COVID-19 pandemic related preventive behaviour by viral load suppression status among people living with HIV during the first wave of the pandemic.

BACKGROUND: Adherence to antiretroviral therapy and COVID-19 preventive behaviours among people living with HIV during the pandemic has received little attention in the literature. To address this gap in knowledge, the present study assessed the associations between viral load, adherence to antiretroviral therapy and the use of COVID-19 prevention strategies during the first wave of the COVID-19 pandemic. This was a secondary analysis of data generated through an online survey recruiting participants from 152 countries. Complete data from 680 respondents living with HIV were extracted for this analysis. RESULTS: The findings suggest that detectable viral load was associated with lower odds of wearing facemasks (AOR: 0.44; 95% CI:0.28-0.69; p < 0.01) and washing hands as often as recommended (AOR: 0.64; 95% CI: 0.42-0.97; p = 0.03). Also, adherence to the use of antiretroviral drugs was associated with lower odds of working remotely (AOR: 0.60; 95% CI: 0.38-0.94; p = 0.02). We found a complex relationship between HIV positive status biological parameters and adherence to COVID-19 preventive measures that may be partly explained by risk-taking behaviours. Further studies are needed to understand the reasons for the study findings.

Barriers and facilitators to anti-retroviral therapy adherence among adolescents aged 10 to 19 years living with HIV in sub-Saharan Africa: A mixed-methods systematic review and meta-analysis.

BACKGROUND: Human Immunodeficiency Virus (HIV) significantly affects adolescents globally, with the sub-Saharan Africa (SSA) reporting a high burden of the disease. HIV testing, treatment, and retention to care are low among adolescents. We conducted a mixed-method systematic review to assess anti-retroviral therapy (ART) adherence; barriers and facilitators to ART adherence and ART outcomes among adolescents living with HIV and on ART in sub-Saharan Africa. METHODS: We conducted searches in four scientific databases for studies conducted between 2010 and March 2022 to identify relevant primary studies. Studies were screened against inclusion criteria and assessed for quality, and data was extracted. Meta-analysis of rates and odd ratios was used to plot the quantitative studies and meta-synthesis summarized the evidence from qualitative studies. RESULTS: A total of 10 431 studies were identified and screened against the inclusion/ exclusion criteria. Sixty-six studies met the inclusion criteria (41 quantitative, 16 qualitative, and 9 mixed-methods study designs). Fifty-three thousand two hundred and seventeen (53 217) adolescents (52 319 in quantitative studies and 899 in qualitative studies) were included in the review. Thirteen support focused interventions for improved ART adherence were identified from quantitative studies. The plotted results from the meta-analysis found an ART adherence rate of 65% (95%CI 56-74), viral load suppression was 55% (95%CI 46-64), un-suppressed viral load rate of 41% (95%CI 32-50), and loss to follow up of 17% (95%CI 10-24) among adolescents. Meta-synthesis found six themes of barriers to ART (social, patient-based, economic, health system-based, therapy-based, and cultural barriers) in both the qualitative and quantitative studies, and three themes of facilitators to ART were also identified (social support, counselling, and ART education and secrecy or confidentiality) from qualitative studies. CONCLUSION: ART adherence remains low among adolescents in SSA despite multiple interventions implemented to improve ART adherence. The low adherence rate may hinder the attainment of the UNAIDS 2030 targets. Additionally, various barriers to ART adherence due to lack of support have been reported among this age group. However, interventions aimed at improving social support, educating, and counselling adolescents may improve and sustain ART adherence. TRIAL REGISTRATION: Systematic review registration: PROSPERO CRD42021284891.

Cohort profile: a longitudinal study of HIV infection in the central nervous system with focus on cerebrospinal fluid - the Gothenburg HIV CSF Study Cohort.

PURPOSE: In order to enable long-term follow-up of the natural course of HIV infection in the central nervous system, a longitudinal cohort study with repeated cerebrospinal fluid (CSF) analyses at intervals over time was initiated in 1985. When antiretrovirals against HIV were introduced in the late 1980s, short-term and long-term effects of various antiretroviral treatment (ART) regimens were added to the study. PARTICIPANTS: All adult people living with HIV (PLWH) who were diagnosed at or referred to the Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden were asked to participate in the Gothenburg HIV CSF Study Cohort. PLWH with neurological symptoms or other clinical symptoms of HIV, as well as those with no symptoms of HIV infection, were included. Most participants were asymptomatic, which distinguishes this cohort from most other international HIV CSF studies. In addition, HIV-negative controls were recruited. These included people on HIV pre-exposure prophylaxis who served as lifestyle-matched controls to HIV-infected men who have sex with men. Since lumbar puncture (LP) is an invasive procedure, some PLHW only consented to participate in one examination. Furthermore, at the beginning of the study, several participants were lost to follow-up having died from AIDS. Of 662 PLWH where an initial LP was done, 415 agreed to continue with follow-up. Among the 415, 56 only gave permission to be followed with LP for less than 1 year, mainly to analyse the short-term effect of ART. The remaining 359 PLWH were followed up with repeated LP for periods ranging from >1 to 30 years. This group was defined as the 'longitudinal cohort'. So far, on 7 April 2022, 2650 LP and samplings of paired CSF/blood had been performed, providing a unique biobank. FINDINGS TO DATE: A general finding during the 37-year study period was that HIV infection in the central nervous system, as mirrored by CSF findings, appears early in the infectious course of the disease and progresses slowly in the vast majority of untreated PLWH. Combination ART has been highly effective in reducing CSF viral counts, inflammation and markers of neural damage. Minor CSF signs of long-term sequels or residual inflammatory activity and CSF escape (viral CSF blips) have been observed during follow-up. The future course of these changes and their clinical impact require further studies. FUTURE PLANS: PLWH today have a life expectancy close to that of non-infected people. Therefore, our cohort provides a unique opportunity to study the long-term effects of HIV infection in the central nervous system and the impact of ART and is an ongoing study.

Impact of COVID-19 on Adolescent HIV Prevention and Treatment Services in the AHISA Network.

We investigated perceived impacts of COVID-19 on the delivery of adolescent HIV treatment and prevention services in sub-Saharan Africa (SSA) by administering a survey to members of the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) from February to April 2021. We organized COVID-19 impacts, as perceived by AHISA teams, under three themes: service interruptions, service adjustments, and perceived individual-level health impacts. AHISA teams commonly reported interruptions to prevention programs, diagnostic testing, and access to antiretroviral therapy (ART). Common service adjustments included decentralization of ART refills, expanded multi-month ART distribution, and digital technology use. Perceived individual-level impacts included social isolation, loss to follow-up, food insecurity, poverty, and increases in adolescent pregnancies and sexually transmitted infections. The need for collaboration among stakeholders were commonly cited as lessons learned by AHISA teams. Survey findings highlight the need for implementation science research to evaluate the effects of pandemic-related HIV service adaptations in SSA.

Barriers to access to antiretroviral therapy by people living with HIV in an indonesian remote district during the COVID-19 pandemic: a qualitative study.

BACKGROUND: Coronavirus disease (COVID-19) pandemic has a significant influence on the access to healthcare services. This study aimed to understand the views and experiences of people living with HIV (PLHIV) about barriers to their access to antiretroviral therapy (ART) service in Belu district, Indonesia, during the COVID-19 pandemic. METHODS: This qualitative inquiry employed in-depth interviews to collect data from 21 participants who were recruited using a snowball sampling technique. Data analysis was guided by a thematic framework analysis. RESULTS: The findings showed that fear of contracting COVID-19 was a barrier that impeded participants' access to ART service. Such fear was influenced by their awareness of their vulnerability to the infection, the possibility of unavoidable physical contact in public transport during a travelling to HIV clinic and the widespread COVID-19 infection in healthcare facilities. Lockdowns, COVID-19 restrictions and lack of information about the provision of ART service during the pandemic were also barriers that impeded their access to the service. Other barriers included the mandatory regulation for travellers to provide their COVID-19 vaccine certificate, financial difficulty, and long-distance travel to the HIV clinic. CONCLUSIONS: The findings indicate the need for dissemination of information about the provision of ART service during the pandemic and the benefits of COVID-19 vaccination for the health of PLHIV. The findings also indicate the need for new strategies to bring ART service closer to PLHIV during the pandemic such as a community-based delivery system. Future large-scale studies exploring views and experiences of PLHIV about barriers to their access to ART service during the COVID-19 pandemic and new intervention strategies are recommended.

The Status of Adolescent Testing and Treatment in PEPFAR-Supported Programs, October 2017 to September 2020.

BACKGROUND: Adolescents have poorer outcomes across the HIV cascade compared with adults. We aimed to assess progress in HIV case finding, antiretroviral treatment (ART), viral load coverage (VLC), and viral load suppression (VLS) among adolescents enrolled in the US President's Emergency Plan for AIDS Relief (PEPFAR)-supported programs over a 3-year period that included the beginning of the COVID-19 pandemic. METHODS: We analyzed PEPFAR program data in 28 countries/regions for adolescents aged 10-19 years between year 1 (October 2017to September 2018), year 2 (October 2018 to September 2019), and year 3 (October 2019 to September 2020). We calculated the number and percent change for HIV tests, HIV-positive tests, and total number on ART. Calculated indicators included positivity, percent of positives newly initiated on ART (ART linkage), VLC (percent of ART patients on ART for ≥6 months with a documented viral load result within the past 12 months), and VLS (percent of viral load tests with <1000 copies/mL). RESULTS: Between years 1 and 3, the number of HIV tests conducted decreased by 44.2%, with a 29.1% decrease in the number of positive tests. Positivity increased from 1.3%-1.6%. The number of adolescents receiving ART increased by 10.4%. In addition, ART linkage increased (77.8%-86.7%) as did VLC (69.4%-79.4%) and VLS (72.8%-81.5%). CONCLUSIONS: Our findings demonstrate PEPFAR's success in increasing the adolescent treatment cohort. We identified ongoing gaps in adolescent case finding, linkage, VLC, and VLS that could be addressed with a strategic mix of testing strategies, optimal ART regimens, and adolescent-focused service delivery models.

The impact of the COVID-19 pandemic on mental health, associated factors and coping strategies in people living with HIV: a scoping review.

INTRODUCTION: The COVID-19 pandemic and associated measures implemented by authorities have created additional stressors and increased the risk of psychological illnesses among people living with HIV (PLWH). Yet, there is no collective evidence on the mental health status of this population during the global pandemic and associated factors. This scoping review aimed to synthesize the evidence in the current literature related to the mental health outcomes and challenges faced by PLWH during the COVID-19 pandemic, identify the associated factors with psychological distress and summarize various coping strategies to ease these psychological distresses used by this population. METHODS: We conducted a scoping review following the PRISMA-ScR guideline and a literature search in four electronic databases in August 2022. Three reviewers independently screened all the search records and extracted the data from studies that met the inclusion criteria. Factors associated with worsened mental health outcomes were synthesized according to the socio-ecological framework. RESULTS: Among 1100 research records, 45 articles met the eligibility criteria and were included in the final review and data extraction, most of which were quantitative analyses. PLWH reported high rates of mental health problems during the pandemic. Multi-level factors were associated with increased psychological distress, including substance use, antiretroviral adherence, social support, financial hardship and economic vulnerability during the pandemic. PLWH used social media as a coping strategy to foster social support to deal with growing mental distress. Increased mental health illnesses were associated with increased substance use, it was also found associated with suboptimal medication adherence and antiretroviral therapy (ART) care engagement. DISCUSSION: PLWH experienced high rates of mental health illnesses, such as depression during the global COVID-19 pandemic. There is an urgent need to provide comprehensive HIV treatment and mental health services as the pandemic continues to evolve. CONCLUSIONS: The review summarized how the mental health of PLWH was affected during the COVID-19 pandemic. Future work in the implementation of effective interventions to promote mental health in this population is needed, not only to ensure their quality of life but also to help them maintain ART adherence and healthcare during more unprecedented times.

Poor adherence to antiretroviral therapy among adult people living with HIV initiated during the COVID-19 epidemic waves - observations at the University Teaching Hospital in Lusaka, Zambia.

Background: Coronavirus disease 2019 (COVID-19)-related disruptions in healthcare services and clinical outcomes have been predicted and documented. However, little is known about how antiretroviral therapy (ART) adherence disruptions caused by the COVID-19 pandemic have manifested amidst the 'Undetectable = Untransmittable' campaign initiative. Using a patient's viral load as a proxy for medication adherence, our study aimed to determine the adherence to ART on first-line medications among adult people living with human immunodeficiency virus (PLWHIV) at the University Teaching Hospital in Lusaka, Zambia during the pandemic. Methods: This was a hospital-based cross-sectional study. Secondary data of PLWHIV registered to receive ART from the Adult Infectious Disease Centre was extracted from the SmartCare® electronic health record system to constitute a resultant data set that this study used. The data extraction form was used to extract values of dependent (ART adherence measured by viral load detectability) and independent variables and imported them into the statistical analysis tool, STATA version 16.1 MP. Descriptive statistics of individual characteristics, testing for associations using Pearson's chi-square test, and stratified and combined multivariable logistic regression were performed. Results: Of the 7,281 adult PLWHIV included in this study, 9.0% (95% CI 8.3-9.6%) were virally detectable. Estimates of the odds ratios of detectable viral load remained significantly higher among adult PLWHIV who were initiated on ART after the U=U campaign was launched in Zambia and were on a monthly 2.51 (1.31-9.03) or 6-monthly 4.75 (3.52-6.41) dispensing of a dolutegravir-based regimen and those on 6-monthly dispensing of an efavirenz-based regimen 4.67 (2.16-10.08) compared to their counterparts. Overall estimates showed us the same picture 4.14 (3.22-5.31), having adjusted for all other predictor variables. Conclusion: We found that a high proportion of people with detectable viral load in the study population, irrespective of medication refill interval and type of regimen, was concentrated among adult PLWHIV who started treatment during the COVID-19 epidemic waves, as compared to those who started treatment before the pandemic. This observed disparity suggests the inherent impact of the pandemic on the adherence to ART among adult PLWHIV in Lusaka, Zambia. This further illustrates how exposed program responses are to external shocks, especially in already weakened health systems, and the need to create program response buffers and resilient program-specific strategies to minimize the effect of external disruptions.

Managers' and providers' perspectives on barriers and facilitators for the implementation of differentiated service delivery models for HIV treatment in Mozambique: a qualitative study.

INTRODUCTION: In 2018, Mozambique's Ministry of Health launched a guideline for a nationwide implementation of eight differentiated service delivery models to optimize HIV service delivery and achieve universal coverage of HIV care and treatment. The models were (1) Fast-track, (2) Three-month Antiretrovirals Dispensing, (3) Community Antiretroviral Therapy Groups, (4) Adherence Clubs, (5) Family-approach, and three one-stop shop models for (6) Tuberculosis, (7) Maternal and Child Health, and (8) Adolescent-friendly Health Services. This study identified drivers of implementation success and failure across these differentiated service delivery models. METHODS: Twenty in-depth individual interviews were conducted with managers and providers from the Ministry of Health and implementing partners from all levels of the health system between July and September 2021. National-level participants were based in the capital city of Maputo, and participants at provincial, district and health facility levels were from Sofala province, a purposively selected setting. The Consolidated Framework for Implementation Research (CFIR) guided data collection and thematic analysis. Deductively selected constructs were assessed while allowing for additional themes to emerge inductively. RESULTS: The CFIR constructs of Relative Advantage, Complexity, Patient Needs and Resources, and Reflecting and Evaluating were identified as drivers of implementation, whereas Available Resources and Access to Knowledge and Information were identified as barriers. Fast-track and Three-month Antiretrovirals Dispensing models were deemed easier to implement and more effective in reducing workload. Adherence Clubs and Community Antiretroviral Therapy Groups were believed to be less preferred by clients in urban settings. COVID-19 (an inductive theme) improved acceptance and uptake of individual differentiated service delivery models that reduced client visits, but it temporarily interrupted the implementation of group models. CONCLUSIONS: This study described important determinants to be addressed or leveraged for the successful implementation of differentiated service delivery models in Mozambique. The models were considered advantageous overall for the health system and clients when compared with the standard of care. However, successful implementation requires resources and ongoing training for frontline providers. COVID-19 expedited individual models by loosening the inclusion criteria; this experience can be leveraged to optimize the design and implementation of differentiated service delivery models in Mozambique and other countries.

Beyond Antiretroviral Treatment: Patterns and Factors Associated With Composite Medication Adherence Before and During the COVID-19 Pandemic in Patients With HIV With Multiple Chronic Conditions.

BACKGROUND: Polypharmacy for multiple chronic conditions (MCCs) poses an increasing challenge in people with HIV (PWH). This research explores medication adherence in PWH with MCCs before and during COVID-19. SETTING: Kaiser Permanente Mid-Atlantic States. METHODS: Medical and pharmacy records of a continuously enrolled cohort (September 2018-September 2021) of adult PWH were used. To estimate medication adherence, monthly proportion of days covered (PDC) was measured individually for antiretrovirals (ARVs), diabetes medications (DMs), renin-angiotensin antagonists (RASMs), and statins (SMs) and combined into composite measures (CMs) with and without ARVs. Descriptive statistics, time-series models, and multivariable population-averaged panel general estimating equations were used to profile trends, effects, and factors associated with adherence. RESULTS: The cohort (n = 543) was predominantly 51-64 years old (59.3%), Black (73.1%), male (69.2%), and commercially insured (65.4%). Two-thirds (63.7%) of patients were taking medications in 2 medication groups (ie, ARVs and either DMs, RASMs, or SMs), 28.9% were taking medications in 3 medication groups, and 7.4% were taking medications in all 4 medication groups. Overall, PDC for CMs without ARVs was 77.2% and 70.2% with ARVs. After March 2020, negative monthly trends in PDC were observed for CMs without ARVs (ß = -0.1%, P = 0.003) and with ARVs (ß = -0.3%, P = 0.001). For CMs with ARVs, Black race (aOR = 0.5; P < 0.001; ref: White) and taking medications for 3 medication groups (aOR = 0.8; P < 0.02; ref: 2) were associated with lower adherence. CONCLUSION: Decreasing medication adherence trends were observed during the COVID-19 pandemic with variations among population subgroups. Opportunity exists to improve medication adherence for non-White populations and those taking medications for MCCs beyond ARVs.

COVID-19 impact on newly initiated and restarted antiretroviral treatment patients in the Eastern Cape, South Africa.

BACKGROUND: Initiating newly diagnosed people living with human immunodeficiency virus (HIV) onto antiretroviral treatment (ART) and retaining patients on treatment are vital to South Africa's ART programme. In 2020, coronavirus disease 2019 (COVID-19) and its accompanying containment (lockdown) measures presented unprecedented challenges to achieving these objectives. AIM: This study describes the impact of COVID-19 and related restrictions on district-level numbers of newly diagnosed people living with HIV and defaulting ART patients. SETTING: Buffalo City Metropolitan Municipality (BCMM) in the Eastern Cape of South Africa. METHODS: Mixed-methods approach: Monthly aggregated electronic patient data (newly initiated and restarted on ART) from 113 public healthcare (PHC) facilities were analysed (December 2019 to November 2020) across varying levels of COVID-19 lockdown regulation periods; telephonic in-depth interviews at 10 rural BCMM PHC facilities were conducted with facility staff, community health workers (CHWs) and intervention personnel. RESULTS: The number of newly initiated ART patients decreased dramatically compared with pre-COVID-19 levels. The overall number of restarted ART patients increased in response to fears of co-infection with COVID-19. Facility-level communications and community outreach promoting HIV testing and treatment were disrupted. Novel approaches to providing services to ART patients were developed. CONCLUSION: Programmes for identifying undiagnosed people living with HIV and services aimed at retaining ART patients in care were profoundly impacted by COVID-19. The value of CHWs was highlighted, as were communication innovations.Contribution: This study describes the impact of COVID-19 and related regulations on HIV testing, ART initiation and adherence to treatment in a District of the Eastern Cape of South Africa.

Evaluation of archived drug resistance mutations in HIV-1 DNA among vertically infected adolescents under antiretroviral treatment in Cameroon: Findings during the COVID-19 pandemic.

BACKGROUND: With the success of antiretroviral therapy (ART), children born with HIV are more likely to reach adolescence. However, frequent non-adherence to ART in adolescents living with HIV (ALHIV) leads to viral replication. Notably, a viraemic infection might lead to archived drug resistance mutations (ADRMs). Hence, within the context of the COVID-19 pandemic, we aimed to compare the patterns of ADRMs in viraemic and non-viraemic vertically infected ALHIV and to assess their immunity to and diagnosis of SARS-CoV-2. METHODS: A comparative study was conducted among COVID-19-unvaccinated ALHIV receiving ART in Yaoundé-Cameroon over the period October 2021 to March 2022. Plasma HIV-RNA was measured using Abbott® m2000rt; HIV-1 genotyping was performed on buffy-coat (HIV-1 DNA) and ADRMs were interpreted using HIVdb.v9.0.1. Patterns of HIV-1 ADRMs were compared between viraemic (≥ 1.60 log10 HIV-1 RNA copies/ml) and non-viraemic (< 1.60 log10 copies/ml) individuals. SARS-CoV-2 antibodies were assessed on whole blood using Abbott Panbio COVID-19 immunoglobulin G/M (IgG/IgM) rapid test and COVID-19 polymerase chain reaction test was performed using nasopharyngeal swab samples. RESULTS: Of the 60 ALHIV [aged 17 (16-19) years, 51.6% female], median ART duration was 14 (12-16) years; 31/55 (56.3%) were exposed to nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART (of whom 19/31 transitioned to dolutegravir-based ART in 2020) and 24/55 (43.6%) were on second-line ART. Forty-two out of 60 (70.0%) ALHIV were non-viraemic; 43/60 (71.6%) were successfully sequenced. Overall the ADRM rate was 62.7% (27/43), with 69.2% (9/13) viraemic and 60.0% (18/30) non-viraemic (p = 0.56). NNRTI-ADRMs were significantly higher among viraemic ALHIV (69.2% vs. 46.7%, p = 0.030). Regarding immunity, those with CD4 nadir < 350 cells/µl had significantly higher rates of ADRMs [adjusted odds ratio (aOR) = 3.20 (1.36-95.53), p = 0.03]. In relation to COVID-19 immunity, overall SARS-CoV-2 IgG seropositivity was 28.3% (17/60), whereas 0% (0/60) were seropositive to IgM; in particular, those with CD4 count nadir ≥ 350 cells/µl had higher odds of SARS-CoV-2 IgG seropositivity [OR =7.85 (2.03-30.28), p < 0.01]. No significant association was found between SARS-CoV-2 IgG seropositivity and HIV-RNA (non-viraemic, 33.3%; viraemic, 16.7%; p = 0.18). SARS-CoV-2 RNA prevalence was 4.5% (2/44). The two positive participants were with low-levels of viral load (Ct > 30) and seropositive to IgG. CONCLUSION: In the context of virological success, the majority of ALHIV harbour ADRMs, essentially driven by NNRTI mutations and low CD4 nadir. During the current pandemic, about one-third of ALHIV were previously exposed to SARS-CoV-2. However, some children might have been exposed and uninfected and others might have been infected but showed no serological response at sampling. These findings support the use of NNRTI-sparing regimens and the implementation of COVID-19 barrier measures targeting ALHIV during such a pandemic.

COVID-19 vaccination in people living with HIV: current data and perspectives.

There is no correlation between HIV per se and other risk factors for severe COVID-19 disease. Pivotal studies have shown that vaccination is one of the effective ways to prevent severe COVID-19 illness in the general population. Studies on people living with HIV (PLWH) are scarce. The majority of these studies with mRNA (BNT126b2 and mRNA-1273) and adenovirus vector (Ad26.COV2.2 and ChAdOx1) vaccines with a low number of patients included shows that PLWH on antiretroviral treatment and with CD4 count > 200/mm³ has a robust immune response. These vaccines are thus effective in preventing severe infection caused by severe acute respiratory syndrome coronavirus 2 in PLWH. However, PLWH with a CD4 count of < 200/mm³ and uncontrolled viral load (VL) seems to have a lower immune response. COVID-19 vaccines are safe in PLWH; adverse effects are mild or moderate, and their incidence is similar to non-HIV people (NHP). The CD4 count decreased significantly and transiently, and the VL rebounded insignificantly in a few patients. A complete vaccination including a third dose is, therefore, recommended. A booster dose with an mRNA vaccine is recommended in PLWH with an advanced stage of their disease.

Effect of HIV status and antiretroviral treatment on treatment outcomes of tuberculosis patients in a rural primary healthcare clinic in South Africa.

BACKGROUND: Tuberculosis (TB) remains the leading cause of death among human immunodeficiency virus (HIV) infected individuals in South Africa. Despite the implementation of HIV/TB integration services at primary healthcare facility level, the effect of HIV on TB treatment outcomes has not been well investigated. To provide evidence base for TB treatment outcome improvement to meet End TB Strategy goal, we assessed the effect of HIV status on treatment outcomes of TB patients at a rural clinic in the Ugu Health District, South Africa. METHODS: We reviewed medical records involving a cohort of 508 TB patients registered for treatment between 1 January 2013 and 31 December 2015 at rural public sector clinic in KwaZulu-Natal province, South Africa. Data were extracted from National TB Programme clinic cards and the TB case registers routinely maintained at study sites. The effect of HIV status on TB treatment outcomes was determined by using multinomial logistic regression. Estimates used were relative risk ratio (RRR) at 95% confidence intervals (95%CI). RESULTS: A total of 506 patients were included in the analysis. Majority of the patients (88%) were new TB cases, 70% had pulmonary TB and 59% were co-infected with HIV. Most of HIV positive patients were on antiretroviral therapy (ART) (90% (n = 268)). About 82% had successful treatment outcome (cured 39.1% (n = 198) and completed treatment (42.9% (n = 217)), 7% (n = 39) died 0.6% (n = 3) failed treatment, 3.9% (n = 20) defaulted treatment and the rest (6.6% (n = 33)) were transferred out of the facility. Furthermore, HIV positive patients had a higher mortality rate (9.67%) than HIV negative patients (2.91%)". Using completed treatment as reference, HIV positive patients not on ART relative to negative patients were more likely to have unsuccessful outcomes [RRR, 5.41; 95%CI, 2.11-13.86]. CONCLUSIONS: When compared between HIV status, HIV positive TB patients were more likely to have unsuccessful treatment outcome in rural primary care. Antiretroviral treatment seems to have had no effect on the likelihood of TB treatment success in rural primary care. The TB mortality rate in HIV positive patients, on the other hand, was higher than in HIV negative patients emphasizing the need for enhanced integrated management of HIV/TB in rural South Africa through active screening of TB among HIV positive individuals and early access to ART among HIV positive TB cases.

HIV at 40: kidney disease in HIV treatment, prevention, and cure.

Four decades after the first cases of HIV were reported, kidney disease remains an important comorbidity in people with HIV (PWH). Both HIV-associated nephropathy and immune complex kidney disease were recognized as complications of HIV infection in the early years before treatment was available. Although the introduction of effective antiretroviral therapy in the late 1990s resulted in dramatic improvements in survival and health in PWH, several commonly used antiretroviral agents have been associated with kidney injury. HIV infection and treatment may also promote the progression of comorbid chronic kidney disease due to traditional risk factors such as diabetes, and HIV is one of the strongest "second hits" for the high-risk APOL1 genotype. Unique considerations in the management of chronic kidney disease in PWH are largely related to the need for lifelong antiretroviral therapy, with potential for toxicity, drug-drug interactions, and polypharmacy. PWH who develop progressive chronic kidney disease are candidates for all modalities of kidney replacement therapy, including kidney transplantation, and at some centers, PWH may be candidates to serve as donors for recipients with HIV. Transplantation of kidney allografts from donors with HIV also offers a unique opportunity to study viral dynamics in the kidney, with implications for kidney health and for research toward HIV cure. In addition, HIV-transgenic animal models have provided important insights into kidney disease pathogenesis beyond HIV, and experience with HIV and HIV-related kidney disease has provided important lessons for future pandemics.

Brief Report: Impact of COVID-19 on Cabotegravir Plus Rilpivirine Long-Acting Dosing Across 6 Ongoing Global Phase IIb and III Clinical Trials.

BACKGROUND: Cabotegravir + rilpivirine long-acting (LA) is a novel antiretroviral therapy (ART) administered intramuscularly monthly or every 2 months by a health care provider. The COVID-19 pandemic presents a potential challenge to patients' ability to attend scheduled clinic visits for dosing administration. SETTING: This analysis evaluated implementation fidelity across 6 phase IIb/III/IIIb cabotegravir + rilpivirine LA clinical trials in 16 countries during the COVID-19 pandemic. METHODS: COVID-19-impacted visits were defined as modified dosing visits for which oral therapy was provided to participants unable to attend the clinic or injection visits that were rescheduled. Data from December 1, 2019, to March 1, 2021, were aggregated and analyzed using descriptive statistics. RESULTS: Of 2127 participants in cabotegravir + rilpivirine LA trials, 1997 (94%) had LA dosing visits proceed as planned during the COVID-19 pandemic. Of 130 (6%) participants with injection visits affected by COVID-19, most were from North America (57%) and Europe (26%). Most participants with COVID-19-impacted visits used oral therapy with cabotegravir + rilpivirine (75%) or alternative oral standard-of-care ART (21%) to maintain continuous ART. The most common reasons for missed visits were clinic closure/staffing constraints (48%) and COVID-19-related travel restrictions (23%). Most (98%) participants who used oral ART maintained virologic suppression; 2 participants had viral load between 50 and 100 copies/mL. CONCLUSION: During the COVID-19 pandemic, most trial participants maintained their LA dosing schedules. Flexibility of the LA dosing regimen, with the ability to switch to oral therapy, facilitated continuous ART provision and implementation fidelity.

48-Week effectiveness and tolerability of dolutegravir (DTG) + lamivudine (3TC) in antiretroviral-naïve adults living with HIV: A multicenter real-life cohort.

BACKGROUND: The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use. METHODS: A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL. RESULTS: 135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic. CONCLUSIONS: In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.

COVID-19 associated changes in HIV service delivery over time in Central Africa: Results from facility surveys during the first and second waves of the pandemic.

INTRODUCTION: The COVID-19 pandemic has impacted population health around the globe, directly and indirectly. The objective of this study was to document changes in HIV care associated with the COVID-19 pandemic at selected clinics in Central Africa, along with clinic-level strategies for minimizing disruptions in HIV care and treatment for people with HIV (PWH). METHODS: A 51-item questionnaire on COVID-19 pandemic-associated changes in HIV service delivery was completed by clinicians involved in HIV care at 21 clinics in five countries participating in Central Africa International epidemiology Databases to Evaluate AIDS (CA-IeDEA). The survey was completed at two timepoints: June-July 2020 and October 2020 to February 2021. Descriptive statistics were used to characterize changes in HIV care and related services. RESULTS: While 81% of sites reported at least one negative consequence of COVID-19 for clinic operations during the first survey, none reported suspending antiretroviral therapy (ART) initiation services for new patients, and 24% reported adopting telemedicine. In the follow-up survey, fewer sites (48%) reported at least one disruption to clinic operations, and more sites reported mitigation strategies, including expanding rapid ART initiation services and providing extra supplies of ART medications to reduce visit frequency. In the follow-up survey, more sites, especially in Rwanda, reported stockouts of commodities, including HIV and viral load testing and HIV pre-exposure prophylaxis. More than one-fifth of sites reported stockouts of second- or third-line ART at each survey timepoint. CONCLUSIONS: While the initial wave of the COVID-19 pandemic resulted in concerning disruptions to HIV service delivery at CA-IeDEA sites, most of these disruptions attenuated over time, and many sites introduced measures to help PWH avoid frequent visits to the clinic for care and medications. The impact of HIV commodity stockouts and clinic mitigation strategies on treatment outcomes needs to be assessed.