Government to Government Model for HIV Service Delivery - An Approach for Country and Program Ownership in Four Provinces of Zambia.

The potential disruption in antiretroviral therapy (ART) services in Africa at the start of the COVID-19 pandemic raised concern for increased morbidity and mortality among people living with HIV (PLHIV). We describe HIV treatment trends before and during the pandemic and interventions implemented to mitigate COVID-19 impact among countries supported by the US Centers for Disease Control and Prevention (CDC) through the President's Emergency Plan for AIDS Relief (PEPFAR). We analysed quantitative and qualitative data reported by 10,387 PEPFAR-CDC-supported ART sites in 19 African countries between October 2019 and March 2021. Trends in PLHIV on ART, new ART initiations and treatment interruptions were assessed. Viral load coverage (testing of eligible PLHIV) and viral suppression were calculated at select time points. Qualitative data were analysed to summarize facility- and community-based interventions implemented to mitigate COVID-19. The total number of PLHIV on ART increased quarterly from October 2019 (n = 7,540,592) to March 2021 (n = 8,513,572). The adult population (≥15 years) on ART increased by 14.0% (7,005,959-7,983,793), while the paediatric population (<15 years) on ART declined by 2.6% (333,178-324,441). However, the number of new ART initiations dropped between March 2020 and June 2020 by 23.4% for adults and 26.1% for children, with more rapid recovery in adults than children from September 2020 onwards. Viral load coverage increased slightly from April 2020 to March 2021 (75-78%) and viral load suppression increased from October 2019 to March 2021 (91-94%) among adults and children combined. The most reported interventions included multi-month dispensing (MMD) of ART, community service delivery expansion, and technology and virtual platforms use for client engagement and site-level monitoring. MMD of ≥3 months increased from 52% in October 2019 to 78% of PLHIV ≥ age 15 on ART in March 2021. With an overall increase in the number of people on ART, HIV programmes proved to be resilient, mitigating the impact of COVID-19. However, the decline in the number of children on ART warrants urgent investigation and interventions to prevent further losses experienced during the COVID-19 pandemic and future public health emergencies.

There is no question that the stigma and discrimination associated with HIV and AIDS can be reduced through intervention. The inclusion of stigma and discrimination reduction as a critical component of achieving an AIDS-free generation in recent UNAIDS, UN and PEPFAR political initiatives is promising. Yet national governments need evidence on effective interventions at the individual, community and societal levels in order to strategically incorporate stigma and discrimination reduction into national AIDS plans. Currently, the heterogeneity of stigma and discrimination reduction approaches and measurement makes it challenging to compare and contrast evaluated interventions. Moving forward, it is critical for the research community to: (1) clearly link intervention activities to the domains of stigma to be shifted; (2) assess the stigma domains in a consistent manner; and (3) link stigma and discrimination reduction with HIV prevention, care and treatment outcomes (e.g., uptake, adherence and retention of ART). These steps would further advance the scientific evidence base of stigma and discrimination reduction and allow for the identification of effective interventions that could be scaled up by national governments. 10.7448/IAS.16.3.18881 © 2013 Grossman C I et al; licensee International AIDS Society Published 13 November 2013 Corresponding author: Cynthia I Grossman, HIV Care Engagement and Secondary Prevention Program, Division of AIDS Research, National Institutes of Mental Health, 6001 Executive Boulevard, RM 6201, MSC 9619, Bethesda, MD 20892, USA. ([email protected])

A pandemic anniversary: 40 years of HIV/AIDS

The aim of this study was to describe and evaluate the impact of the programme intervention of the Rivers State Antiretroviral Treatment (ART) Surge, a collaboration between the US President's Emergency Plan for AIDS Relief (PEPFAR) and the State Ministry of Health, to increase HIV case-finding and ART access in Rivers State, the state with the largest ART gap among people living with HIV (PWH) in Nigeria. During April 2019-September 2020, the intervention included six specific strategies: using local government area-level ART gap analysis to guide case-finding; expanding targeted community testing; tailoring comprehensive key population HIV services; engaging HIV treatment programme stakeholders; synchronizing team efforts; and using near real-time data for programme action. Weekly reported facility and community data on tests conducted, PWH diagnosed, and PWH initiated on ART were aggregated. The total number of PWH maintained on ART was reported quarterly. During May 2019-September 2020, the weekly number of newly diagnosed PWH initiated on ART supported by PEPFAR in Rivers State increased from 82 to 1723. During October 2019-September 2020, the monthly number of people screened for HIV testing eligibility in the community increased from 44 000 to 360 000. During April 2019-September 2020, the total number of PWH on ART supported by PEPFAR statewide increased by 3.8 times, from 26 041 to 99 733. The strategies applied by HIV program stakeholders contributed to scale-up of PWH identification and ART linkage within the Rivers State ART Surge. Continued gains through time indicate the importance of the application of a quality improvement approach to maintain programme flexibility and effectiveness.

Tuberculosis preventive treatment (TPT) is a critical intervention to reduce tuberculosis mortality among people living with HIV (PLHIV). To facilitate scale-up of TPT among PLHIV, the Nigeria Ministry of Health and the US Centers for Disease Control and Prevention (CDC) Nigeria, supported by US President's Emergency Plan for AIDS Relief implementing partners, launched a TPT-focused technical assistance strategy in high-volume antiretroviral treatment (ART) sites during 2018. Nigeria has an estimated 1.9 million PLHIV, representing the second largest national burden of PLHIV in the world, and an estimated 53% of PLHIV are on ART. In 50 high-volume ART sites, we assessed readiness for TPT scale-up through use of a standardized tool across the following 5 areas: clinical training, community education, patient management, commodities and logistics management, and recording and reporting. We deployed a site-level continuous quality improvement strategy to facilitate TPT scale-up. Implementing partners rapidly disseminated best practices from these sites to across all CDC-supported sites and reported aggregate data on monthly TPT initiations. Through this targeted assistance and rapid dissemination of best practices to all other sites, the number of PLHIV who initiated TPT across all CDC-supported sites increased from 6622 in May 2018, when the approach was implemented, to 48,661 in September 2018. Gains in monthly TPT initiations were sustained through March 2019. Use of a standardized tool for assessing readiness for TPT scale-up provided a "checklist" of potential barriers to TPT scale-up to address at each site. The quality improvement approach allowed each site to design a specific plan to achieve desired TPT scale-up, and best practices were implemented concurrently at other, smaller sites. The approach could assist scale-up of TPT among PLHIV in other countries.

What Might Surviving Coronavirus Disease 2019 Look Like for People Living with HIV?

Delle Donne, Valentina MPsych, PhD; Massaroni, Valentina MPsych; Ciccarelli, Nicoletta MPsych, PhD; Lombardi, Francesca MBiol, PhD; Lamonica, Silvia MPharm; Borghetti, Alberto MD; Ciccullo, Arturo MD; Di Giambenedetto, Simona MD Author Information

BackgroundAlthough fatigue is a known symptom for people living with HIV (PWH) and a side effect of antiretroviral therapy (ART), its burden upon PWH is not well understood. We aimed to look at the impact of fatigue on quality of life (QoL) in PWH.MethodsData were drawn from the Adelphi Real World HIV Disease Specific Programme™, a cross-sectional survey, with retrospective data collection, of physicians and PWH in France, Germany, Italy, Spain, the United Kingdom and the United States from July 2021 – February 2024. Physicians reported demographics, clinical characteristics, fatigue as a side effect of ART and ART satisfaction for ten consecutively consulting PWH. PWH self-reported ART satisfaction, adherence via the Adelphi Adherence Questionnaire (ADAQ; scored 0–4, with 0 being perfect adherence) and QoL via PoZQoL (scored 0–5, with 5 being best QoL). Analyses were descriptive.ResultsOverall, 335 physicians reported on 3373 PWH, of whom 1008 self-reported data. Mean (standard deviation; SD) patient age was 42.8 (12.8) years and 72% were cisgender male.A total of 1913 PWH had no fatigue (NF) and 423 PWH had moderate to severe fatigue (MSF) due to ART. In total, 65% of MSF PWH were virally suppressed, 29% had no comorbidities and 32% had no side effects. For NF PWH, this was 81%, 54% and 87% of patients, respectively.Physicians were very satisfied with current ART for 78% of NF PWH compared to only 36% of MSF PWH. A total of 79% of physicians thought NF PWH were completely adherent compared to 48% for MSF PWH.Complete satisfaction with ART was reported by 63% of NF PWH compared to 31% of MSF PWH. Mean (SD) ADAQ scores were 0.2 (0.3) for NF PWH and 0.6 (0.6) for MSF PWH. Mean (SD) PozQoL scores were 3.6 (0.7) for NF PWH and 2.6 (0.7) for MSF PWH.ConclusionMSF was associated with low physician and PWH satisfaction with current ART, as well as low adherence and QoL scores. MSF PWH also commonly experienced comorbidities and treatment side effects, with fewer than half of PWH fully adherent to their treatment. Fatigue should be addressed as a prominent clinical burden in the treatment of PWH, with future research elucidating the link between fatigue severity and ART type.DisclosuresAll Authors: No reported disclosures

The prevalence and incidence of tuberculosis (TB) is high among people living with HIV (PLWH) but is often underdiagnosed in HIV programmatic settings. President's Emergency Plan for AIDS Relief (PEPFAR)-supported research sites in Uganda, Kenya, Tanzania, and Nigeria. All patients underwent molecular testing at entry into a longitudinal cohort of PLWH and annually thereafter. We assessed the prevalence and incidence of TB and identified clinical and demographic factors associated with prevalent and incident TB using logistic regression and Cox proportional hazard models. From 21 January, 2013, to 1 December 2021, 3171 PLWH were enrolled with a TB prevalence of 3% (n = 93). Of the cases with prevalent TB, 66% (n = 61) were bacteriologically confirmed. The adjusted odds of prevalent TB were significantly higher among those with higher educational attainment, PLWH for 1-5 years since their HIV diagnosis, those who were underweight, and those with CD4 counts <200 cells/mm 3 . The overall TB incidence rate was 600 per 100,000 person-years (95% CI: 481-748). We found that shorter time since HIV diagnosis, being underweight, taking antiretroviral therapy <6 months, and having a CD4 count <200 cells/mm 3 were significantly associated with incident TB. PLWH on dolutegravir/lamivudine/tenofovir had a 78% lower risk of incident TB compared with those on tenofovir/lamivudine/efavirenz (hazard ratio: 0.22; 95% CI: 0.08-0.63). The prevalence and incidence of TB was notably high in this cohort sourced from PEPFAR clinics. Aggressive efforts to enhance HIV diagnosis and optimize treatment in programmatic settings are warranted to reduce the risk of HIV-TB co-occurrence in this cohort.

tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study examined TB treatment outcomes and their predictive factors among people living with HIV (PLHIVs). a review of TB/HIV co-infected patients who had TB treatments across comprehensive antiretroviral therapy (ART) sites with ≥500 patients was conducted in seven United States of America President's Emergency Plan for AIDS Relief (PEPFAR)-supported States in Nigeria. Data on patient background, HIV and TB care, and TB treatment outcomes were collected using an Excel abstraction template. The data was analyzed using SPSS and an association was examined using a chi-square test while binary logistic regression was used to determine predictors of TB treatment outcomes (P< 0.05). two thousand six hundred and fifty-two co-infected patients participated in the study. The mean age of participants was 37 ± 14 years. A majority had TB treatment success (cured = 1059 (39.9%), completed = 1186 (44.7%)). Participants who had pulmonary TB, virally suppressed and commenced isoniazid (INH) before TB diagnosis were more likely to have a favorable TB treatment outcome compared to those who had extrapulmonary TB (AOR = 7.110, 95% CI = 1.506 - 33.565), virally unsuppressed (AOR = 1.677, 95% CI = 1.036 - 2.716) or did not commence INH before TB diagnosis (AOR = 1.486, 95% CI = 1.047 - 2.109). site of infection, immune status, exposure to ART, and INH prophylaxis were found to predict TB treatment outcomes among PLHIVs. Stakeholders should ensure early commencement of ART and INH prophylaxis for PLHIVs.

In recent decades, progress has been made worldwide in the prevention and control of HIV infection. What is the status of HIV prevention and control in China? This issue of HIV Medicine highlights the current progress in the management of and clinical research on HIV/AIDS in China, providing readers with a brief overview of this field. The Chinese authorities have made several efforts regarding the prevention and treatment of AIDS. For example, HIV infections transmitted by illegal blood transfusions have been eradicated, and HIV transmission among injecting drug users (IDUs) has been markedly reduced due to the implementation of a needle and syringe exchange programme. With the launch of the National Free Antiretroviral Treatment (ART) Program in 2003 and the subsequent implementation of the Four Free and One Care policy in 2006 [1], people living with HIV (PLWH) are often diagnosed via voluntary HIV testing or routine health examinations and provided free access to ART. The Four Free and One Care policy covers the provision of free ART to rural and urban residents without medical insurance; free voluntary counselling and HIV testing; free prevention of mother-to-child transmission; free schooling for orphaned children of PLWH; and care and economic assistance to PLWH with financial difficulties. In particular, the immediate initiation of ART in PLWH since 2016 has significantly reduced not only HIV transmission and prevalence but also AIDS-associated mortality [2]. Two studies in this issue analysed the clinical characteristics of patients receiving ART and pointed out the challenges faced by healthcare providers in China. Zhao et al. [3] presented the demographic and clinical characteristics of the national ART cohort for 2019. Their study showed great progress in increasing ART coverage and provided evidence of viral suppression across China. However, key populations of PLWH still face challenges: many are IDUs, have a history of treatment failure, or are co-infected with hepatitis C virus. Liu et al. [4] analysed the barriers to early diagnosis and timely ART initiation among PLWH, and their findings indicate the need for additional screening and intervention to improve the clinical management of HIV/AIDS. Co-infection with other viruses and bacteria among PLWH is associated with an increased incidence of failed immune reconstitution during ART and leads to a mortality rate higher than that associated with HIV infection alone. Two papers highlighted coinfections with hepatitis B virus (HBV) and Mycobacterium tuberculosis in PLWH. Jiang et al. [5] examined the factors associated with immune reconstitution in individuals with HIV/HBV co-infection receiving ART. They found that the baseline HIV viral load was the only significant factor that negatively influenced CD4 T-cell restoration in this population. Qi et al. [6] investigated tuberculosis (TB)-associated mortality within 90 days of admission and its risk factors among PLWH. Their data showed the 90-day mortality rate in patients with co-infection to be 13.6%, and early TB-associated death was associated with central nervous system TB, not receiving ART within 3 months after admission, and serum albumin levels < 25 g/L. In the era of ART, mother-to-child HIV transmission has substantially decreased. However, anti-HIV antibodies may still be detected in uninfected infants of mothers with chronic HIV infection. On monitoring the dynamics of anti-HIV antibodies in these infants, Liu et al. [7] noted the clearance of anti-HIV antibodies at more than 18 months post-delivery in 5.8% of uninfected children. These findings indicate that positive results for anti-HIV antibodies in infants aged 18–24 months should be carefully interpreted. Simultaneously, additional nucleic acid tests are necessary to confirm a diagnosis of HIV infection. Although ART has increased the life expectancy and improved the quality of life of PLWH, non-AIDS-associated events remain an issue. Lin et al. [8] summarized the clinical characteristics of non-AIDS-associated events involving multiple organs, such as the liver and kidneys, and suggested that multidisciplinary management is necessary for PLWH. Ying et al. [9] investigated the epidemiology, clinical features, and prognostic factors of HIV-associated talaromycosis and found an increased prevalence in Guangdong, China. Typical skin lesions were noted in 44.5% of patients. Induction therapy with azole alone was associated with a higher mortality than therapy with amphotericin B deoxycholate. These results may serve as a guide for clinicians in the management of HIV-associated talaromycosis. The viral reservoir is the biggest hurdle in the race to cure HIV/AIDS. In the shock and kill strategy, the latent HIV reservoir is maximally activated by stimulation with latency reversal agents and further cleared by host immune surveillance. Li et al. [10] evaluated the safety and efficacy of chidamide, a histone deacetylase inhibitor, for HIV-1 latency reversal in seven participants with viral suppression. All participants exhibited robust and repeated plasma viral rebound and increased cell-associated HIV-1 RNA levels, but only grade 1 adverse events were reported. Chidamide seems to be an effective agent in disrupting HIV-1 latency and reducing HIV-1 DNA loads; however, these findings need to be confirmed in randomized controlled clinical trials. Zhang et al. [11] summarized recent findings regarding the role of CD8 T-cells in controlling HIV infection, highlighting the differences between conventional antigen-specific and innate-like CD8 T-cells. Antiviral activity of CD8 T-cells in PLWH receiving ART may not be achieved via an antigen-specific approach, as HIV-specific CD8 T-cells can sense, but not effectively eliminate, cells harbouring intact proviruses. By contrast, virtual memory CD8 T-cells, a semi-differentiated subset of CD8 T-cells, may be involved in controlling the HIV DNA reservoir in patients receiving ART. In China, although remarkable progress has been made in controlling the HIV epidemic, challenges remain. First, the absolute number of PLWH is approximately 1.2 million, and the annual number of newly identified HIV/AIDS cases has been determined to be 150 000 in the last 3 years. In particular, approximately 31% of PLWH were diagnosed in the advanced stage, with peripheral CD4 T-cell counts of less than 200 cells/µL [3, 12]. In-time HIV screening is necessary to identify PLWH at an early stage. Second, the choice of ART drugs for PLWH is limited; for example, integrase inhibitors have recently been included in the free ART regimen, but this programme does not cover all PLWH. Third, sexual transmission has become the main route of HIV spread, and such transmission needs to be reduced by efficient preventive programmes, such as those providing universal pre-exposure prophylaxis. The 90-90-90 goals put forth by the Joint United Nations Program on AIDS/HIV seek for 90% of PLWH to be diagnosed, 90% of those diagnosed to receive ART, and 90% of those receiving ART to show viral suppression. It is feasible to achieve these 90-90-90 goals during next 5 years in China, but we still have a long way to go for the development of a cure for HIV infection.

Human immunodeficiency virus (HIV) infection remains a major health burden in Sub-Saharan Africa, despite the widespread use of antiretroviral therapy (ART). Oxidative stress contributes to HIV-related comorbidities, including renal dysfunction. However, the role of oxidative stress in kidney impairment among people living with HIV (PLWH) is not fully understood. This cross-sectional study included PLWH on ART (n = 80), PLWH without ART (n = 27), and people not living with HIV (PNLWH) (n = 44). Oxidative stress was measured by serum malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (TAC), while renal function was assessed using cystatin C-based estimated glomerular filtration rate (eGFRcystC). Participants on ART were older (median 43 years) and had higher CD4+ T-cell counts compared to those not on ART. PLWH on ART showed significantly elevated MDA levels compared to PLWH without ART (p < 0.001) and PNLWH (p = 0.001). There was no difference in superoxide dismutase (SOD) and TAC levels among the groups (p = 0.177 and 0.888, respectively). Among PLWH, MDA was higher in those with reduced renal function (eGFRcystC < 90) versus normal function (p < 0.05). In PLWH on ART, SOD activity was significantly lower in mild renal impairment (eGFRcystC 60–89) compared to normal function (p = 0.017), but no difference was observed in the TAC levels (p = 0.883). In PLWH on ART, regression analyses indicated no independent association between MDA and renal function decline, while higher SOD activity independently predicted better renal function (adjusted β = 2.26, p = 0.042). Oxidative damage accompanied by the inability of the body’s primary antioxidant defenses may be present at the early onset of renal function decline in PLWH. Superoxide dismutase, as an antioxidant defence enzyme, may be a key contributor to renal health in PLWH on ART. Future studies with larger cohorts and longitudinal designs are needed to clarify these relationships emanating from this pilot study.

Antiretroviral Therapy and Tuberculosis: What's the Connection and What's the Way Forward?

Adolescents aged 10-19 years account for a growing proportion of people living with HIV (PLHIV). In 2023, 140,000 adolescents were diagnosed with HIV, yet knowledge of HIV status and uptake of testing services remain critically low. Index testing-offering testing to contacts of PLHIV-is an important case-finding strategy. In 2021, President's Emergency Plan for AIDS Relief expanded guidance to explicitly include older adolescents aged 15-19 years. We reviewed index testing data to assess uptake and case-finding trends among biological adolescent-aged children and siblings of PLHIV aged 10-19 years. Routinely collected programmatic data from 27 U.S. Agency for International Development-supported President's Emergency Plan for AIDS Relief country and regional programs were analyzed for fiscal years (FY) 2017 through FY2022 (October 2016-September 2022). We compared the volume of index testing and subsequent new diagnoses across FYs and countries among biological adolescent-aged children and siblings of PLHIV and disaggregated by age, 10-14 and 15-19 years, and sex. Index testing among adolescents aged 10-19 years increased from FY17 to FY22, nearly doubling from 147,088 to 291,534. Similarly, new diagnoses among adolescents increased between FY17 and FY22 (3721 vs 10,730). Overall, across FYs, index testing uptake and case-finding were higher among females than males, and the gap in testing uptake between sexes was larger for older than younger adolescents. Index testing uptake has increased substantially among adolescents over time, with rebounded gains for adolescents aged 15-19 years noted beginning in FY21. However, uptake across age and sex remained uneven, highlighting an opportunity to ensure that targeted testing strategies are used to reach adolescents aged 15-19 years and males.

This editorial comments on the article by Miller et al.