Identifying barriers to ART initiation and adherence: An exploratory qualitative study on PMTCT in Zambia

Background Though antiretroviral therapy (ART) is widely available, HIV positive pregnant women in Zambia are less likely to start and remain on therapy throughout pregnancy and after delivery. This study sought to understand readiness to start ART among HIV pregnant women from the perspectives of both women and men in order to suggest more holistic programs to support women to continue life-long ART after delivery. Methods We conducted a qualitative study with HIV positive pregnant women before and after ART initiation, and men with female partners, to understand readiness to start lifelong ART. We conducted 28 in-depth interviews among women and 2 focus group discussions among male partners. Data were transcribed verbatim and analyzed in NVivo 12 using thematic analysis. Emerging themes from the data were organized using the social ecological framework. Results Men thought of their female partners as young and needing their supervision to initiate and stay on ART. Women agreed that disclosure and partner support were necessary preconditions to ART initiation and adherence and, expressed fear of divorce as a prominent barrier to disclosure. Maternal love and desire to look after one’s children instilled a sense of responsibility among women which motivated them to overcome individual, interpersonal and health system level barriers to initiation and adherence. Women preferred adherence strategies that were discrete, the effectiveness of which, depended on women’s intrinsic motivation. Conclusion The results support current policies in Zambia to encourage male engagement in ART care. To appeal to male partners, messaging on ART should be centered on emphasizing the importance of male involvement to ensure women remain engaged in ART care. Programs aimed at supporting postpartum ART adherence should design messages that appeal to both men’s role in couples’ joint decision-making and women’s maternal love as motivators for adherence.

Dynamics of latent HIV under clonal expansion

The HIV latent reservoir exhibits slow decay on antiretroviral therapy (ART), impacted by homeostatic proliferation and activation. How these processes contribute to the total dynamic while also producing the observed profile of sampled latent clone sizes is unclear. An agent-based model was developed that tracks individual latent clones, incorporating homeostatic proliferation of cells and activation of clones. The model was calibrated to produce observed latent reservoir dynamics as well as observed clonal size profiles. Simulations were compared to previously published latent HIV integration data from 5 adults and 3 children. The model simulations reproduced reservoir dynamics as well as generating residual plasma viremia levels (pVL) consistent with observations on ART. Over 382 Latin Hypercube Sample simulations, the median latent reservoir grew by only 0.3 log10 over the 10 years prior to ART initiation, after which time it decreased with a half-life of 15 years, despite number of clones decreasing at a faster rate. Activation produced a maximum size of genetically intact clones of around one million cells. The individual simulation that best reproduced the sampled clone profile, produced a reservoir that decayed with a 13.9 year half-life and where pVL, produced mainly from proliferation, decayed with a half-life of 10.8 years. These slow decay rates were achieved with mean cell life-spans of only 14.2 months, due to expansion of the reservoir through proliferation and activation. Although the reservoir decayed on ART, a number of clones increased in size more than 4,000-fold. While small sampled clones may have expanded through proliferation, the large sizes exclusively arose from activation. Simulations where homeostatic proliferation contributed more to pVL than activation, produced pVL that was less variable over time and exhibited fewer viral blips. While homeostatic proliferation adds to the latent reservoir, activation can both add and remove latent cells. Latent activation can produce large clones, where these may have been seeded much earlier than when first sampled. Elimination of the reservoir is complicated by expanding clones whose dynamic differ considerably to that of the entire reservoir.

HIV testing and ART initiation among partners, family members, and high-risk associates of index clients participating in the CommLink linkage case management program, Eswatini, 2016–2018

To help diagnose and initiate antiretroviral therapy (ART) for ≥95% of all persons living with HIV (PLHIV), the World Health Organization (WHO) recommends offering HIV testing to biological children, and sexual and needle-sharing partners of all PLHIV (index-client testing, ICT). Many index clients, however, do not identify or have contactable partners, and often substantially fewer than 95% of HIV-positive partners initiate ART soon after index testing. To help improve early HIV diagnosis and ART initiation in Eswatini (formerly Swaziland), we implemented a community-based HIV testing and peer-delivered, linkage case management program (CommLink) that provided ICT as part of a comprehensive package of WHO recommended linkage services. CommLink was implemented June 2015 –March 2017 (Phase I), and April 2017 –September 2018 (Phase II). In addition to biological children and partners, HIV testing was offered to adult family members (Phases I and II) and high-risk associates including friends and acquaintances (Phase II) of CommLink index clients. Compared with Phase I, in Phase II proportionally more CommLink clients disclosed their HIV-infection status to a partner or family member [94% (562/598) vs. 75% (486/652)], and had ≥1 partners, family members, or high-risk associates (contacts) tested through CommLink [41% (245/598) vs. 18% (117/652)]. Of 537 contacts tested, 253 (47%) were HIV-positive and not currently in HIV care, including 17% (17/100) of family members aged <15 years, 42% (78/187) of non-partner family members aged ≥15 years, 60% (73/121) of sexual partners, and 66% (85/129) of high-risk associates. Among 210 HIV-positive contacts aged ≥15 years who participated in CommLink, nearly all received recommended linkage services including treatment navigation (95%), weekly telephone follow-up (93%), and ≥3 counseling sessions (94%); peer counselors resolved 76% (306/404) of identified barriers to care (e.g., perceived wellness); and 200 (95%) initiated ART at a healthcare facility, of whom 196 (98%) received at least one antiretroviral refill before case-management services ended. To help countries achieve ≥90% ART coverage among all PLHIV, expanding ICT for adult family members and high-risk associates of index clients, and providing peer-delivered linkage case management for all identified PLHIV, should be considered.

Association between rectal gonorrhoea and HIV incidence in men who have sex with men: a meta-analysis

BackgroundIncidence of rectal gonorrhoea (GC) has been hypothesised as a correlate of HIV exposure in prevention trials of men who have sex with men (MSM). High rectal GC incidence in MSM trials of new biomedical prevention drugs may provide supportive evidence for ongoing HIV risk. Empirical evidence of correlation between rectal GC and HIV incidence is needed to assess whether high rectal GC rates reliably correlate with high risk of HIV.MethodsRectal GC and HIV are routinely tested in sexual health clinics (SHCs) throughout England. Through routine surveillance data collected at visits to SHCs, we assessed HIV incidence and new rectal GC diagnoses in repeat visits by HIV-negative MSM between 2011 and 2018, predating widespread roll-out of pre-exposure prophylaxis. Meta-analysis regression assessed population-level association between HIV and rectal GC incidence over time.FindingsBetween 2011 and 2018, HIV and rectal GC incidence was assessed in 541 056 HIV-negative MSM attending SHCs in England. HIV incidence among MSM attending SHCs fell from 1.26/100 person-years (PYs) in 2011 to 0.28/100 PYs in 2018. Rectal GC rates increased from 3.5/100 PYs to 11.1/100 PYs over the same period. The rate of HIV incidence decreased by 22.3% for each percent increase in rectal GC (95% CI –30.8 to –14.7, p<0.001).InterpretationAmong the population of MSM attending SHCs in England, rectal GC rates increased substantially while HIV incidence rates decreased between 2011 and 2018. HIV incidence likely decreased through expanded HIV testing, prompt antiretroviral treatment (ART) initiation and increased viral suppression in persons living with HIV, interventions that did not decrease rectal GC. Rectal GC may not be an ideal proxy for HIV incidence in trials, as HIV exposure risk is complex and context dependent, given effective HIV prevention interventions in MSM.Introduction

Gaps in the continuum of care among people living with HIV in Afghanistan

Background Afghanistan adopted a “test and treat” strategy for all people living with HIV (PLWH) in 2016. In this study, we presented demographic and clinical characteristics of all people diagnosed between 2013 and 2019 and evaluated progress towards 90-90-90 UNAIDS targets and identified program gaps among PLWH in Afghanistan diagnosed in 2018. Methods We used clinical, behavioral, and demographic data from national HIV surveillance for 1394 patients diagnosed from 2013 through 2019. We also tracked 184 patients diagnosed with HIV in 2018 over 15 months to assess their enrollment in care, antiretroviral therapy (ART) initiation, retention on ART, and viral suppression. Results Of 1394 patients diagnosed from 2013 through 2019, 76.0% were male, 73.7% were older than 24 years, and 33.4% acquired HIV through heterosexual sex. Of the 184 patients diagnosed in 2018, 94.6% were enrolled in care, 88.6% received ART, 84.2% were retained on ART for at least 12 months, and 33.7% received a viral load test. Of those with a viral load test, 74.2% were virally suppressed. Patients who were 35–44 years old (52.0%, p-value .001), acquired HIV through unsafe injection (62.5%, p-value .413), were co-infected with hepatitis C virus (HCV) (60.0%, p-value .449), and with CD4 > 500 at diagnosis (64.7%, p-value .294) were less likely to be virally suppressed 12 months after diagnosis. Conclusion Nearly 95% of people diagnosed with HIV in Afghanistan in 2018 were linked to care and nearly 90% were on ART. Viral testing and viral suppression remain low with notable disparities for middle-aged patients, and possibly for those who injected drugs. Addressing barriers to HIV programs in Afghanistan, particularly for people who inject drugs (PWID), are urgently needed to reach the 90-90-90 global targets. Surveillance data on the number of people with undiagnosed HIV is needed to assess the first 90 target.

The burden of neuropsychiatric disorders in patients living with HIV-1 treated with antiretroviral therapies—A perspective from US Medicaid data

Background People with human immunodeficiency virus (HIV)-1 face challenges with treatment adherence for various reasons, including consideration of neuropsychiatric disorders and neuropsychiatric adverse reactions associated with antiretroviral therapy (ART). Methods A retrospective cohort study was conducted using administrative claims data from the IBM MarketScan® Multi-State Medicaid Database (1/1/2014–12/31/2017). Adults (≥18 years) diagnosed with HIV-1 and newly initiated on antiretroviral therapy with continuous health plan enrollment were included. Primary outcome was the 6-month period prevalence of neuropsychiatric events (NPEs) of interest after ART initiation. Results Among 1971 newly treated patients included in the study, mean age (standard deviation [SD]) was 38.5 (12.7) years, and 41.4% were female. During the 6 months after ART initiation, 51.4% of patients had a claim for ≥1 NPE versus 30.3% of matched patients without HIV. Among newly treated patients, the most common (≥10%) NPE claims were for depression (42.2%), anxiety (15.8%), headache (11.9%), and bipolar/manic depression (10.1%). Also in this group, the mean (SD) total all-cause healthcare cost during the 6-month post-ART initiation was $16,632 ($33,928), of which $2914 ($18,233) was NPE-related. Conclusions In summary, in this Medicaid study of people newly initiated on ART, there was a high prevalence of NPEs, and incremental NPE-associated costs were considerable.

HBV co-infection is associated with persistently elevated liver stiffness measurement in HIV-positive adults: A 6-year single-centre cohort study in Nigeria

Background In Nigeria, the effect of Hepatitis B virus (HBV) on long-term liver outcomes in persons with HIV (PLH) has not been described. We determined changes in liver stiffness measure (LSM) using transient elastography over 6 years in HIV mono-infected and HIV-HBV co-infected Nigerians initiating antiretroviral therapy (ART) and factors associated with LSM decline. Methods This single centre, cohort study enrolled ART-naïve HIV mono- and HIV-HBV co-infected adults (≥18 years) at the APIN Public Health Initiatives–supported HIV Care and Treatment Centre at Jos University Teaching Hospital, Nigeria, from 7/2011 to 2/2012. LSM at baseline, Years 3 and 6 were analysed using longitudinal models to estimate changes over time and their predictors. Results Data from 100 (31%) HIV-HBV co-infected and 225 (69%) HIV mono-infected participants were analysed. Median LSM at baseline was 6.10 (IQR: 4.60–7.90) kPa in co-infected and 5.10 (IQR: 4.40–6.10) kPa in mono-infected participants. In adjusted analyses, average LSM was not significantly different between Year 0 and 3 (β = 0.02, −0.22 to 0.26, p = 0.87 and Year 0 and 6 (β = −0.02, −0.23 to 0.27, p = 0.88) in both groups ( p>0.05), but co-infected participants had significantly higher LSM than mono-infected throughout follow-up (β = 0.018, 0.019–0.28, p < 0.001). Year 3 LSM differed according to ART initiation status by Year 3 (initiators - non-initiators: −0.87, −1.70 to −0.29). Conclusion In this cohort, LSM remained higher among HIV-HBV co-infected versus HIV mono-infected participants throughout follow-up. Our findings emphasize the continuing need for monitoring of liver outcomes in HIV-HBV co-infected populations on ART and the importance of preventing HBV infection among PLH to optimize liver health.

The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China

Background: The optimal timing for initiation of antiretroviral therapy (ART) in HIV-positive patients with cryptococcal meningitis (CM) has not, as yet, been compellingly elucidated, as research data concerning mortality risk and the occurrence of immune reconstitution inflammatory syndrome (IRIS) in this population remains inconsistent and controversial.Method: The present multicenter randomized clinical trial was conducted in China in patients who presented with confirmed HIV/CM, and who were ART-naïve. Subjects were randomized and stratified into either an early-ART group (ART initiated 2–5 weeks after initiation of antifungal therapy), or a deferred-ART group (ART initiated 5 weeks after initiation of antifungal therapy). Intention-to-treat, and per-protocol analyses of data for these groups were conducted for this study.Result: The probability of survival was found to not be statistically different between patients who started ART between 2–5 weeks of CM therapy initiation (14/47, 29.8%) vs. those initiating ART until 5 weeks after CM therapy initiation (10/55, 18.2%) (p = 0.144). However, initiating ART within 4 weeks after the diagnosis and antifungal treatment of CM resulted in a higher mortality compared with deferring ART initiation until 6 weeks (p = 0.042). The incidence of IRIS did not differ significantly between the early-ART group and the deferred-ART group (6.4 and 7.3%, respectively; p = 0.872). The percentage of patients with severe (grade 3 or 4) adverse events was high in both treatment arms (55.3% in the early-ART group and 41.8% in the deferred-ART group; p=0.183), and there were significantly more grade 4 adverse events in the early-ART group (20 vs. 13; p = 0.042).Conclusion: Although ART initiation from 2 to 5 weeks after initiation of antifungal therapy was not significantly associated with high cumulative mortality or IRIS event rates in HIV/CM patients compared with ART initiation 5 weeks after initiation of antifungal therapy, we found that initiating ART within 4 weeks after CM antifungal treatment resulted in a higher mortality compared with deferring ART initiation until 6 weeks. In addition, we observed that there were significantly more grade 4 adverse events in the early-ART group. Our results support the deferred initiation of ART in HIV-associated CM.Clinical Trials Registration:www.ClinicalTrials.gov, identifier: ChiCTR1900021195.

Timely initiation of HIV antiretroviral therapy in Haiti 2004–2018: a retrospective cohort study

Objective. To describe trends in timing of ART initiation for newly diagnosed people living with HIV before and after Haiti adopted its Test and Start policy for universal HIV antiretroviral therapy (ART) in July 2016, and to explore predictors of timely ART initiation for both newly and previously diagnosed people living with HIV following Test and Start adoption. Methods. This retrospective cohort study explored timing of ART initiation among 147 900 patients diagnosed with HIV at 94 ART clinics in 2004–2018 using secondary electronic medical record data. The study used survival analysis methods to assess time trends and risk factors for ART initiation. Results. Timely uptake of ART expanded with Test and Start, such that same-day ART initiation rates increased from 3.7% to 45.0%. However, only 11.0% of previously diagnosed patients initiated ART after Test and Start. In adjusted analyses among newly diagnosed people living with HIV, factors negatively associated with timely ART initiation included being a pediatric patient aged 0–14 years (HR = 0.23, p < 0.001), being male (HR = 0.92, p = 0.03), being 50+ years (HR = 0.87, p = 0.03), being underweight (HR = 0.79, p < 0.001), and having WHO stage 3 (HR = 0.73, p < 0.001) or stage 4 disease (HR = 0.49, p < 0.001). Variation in timely ART initiation by geographic department and health facility was observed. Conclusions. Haiti has made substantial progress in scaling up Test and Start, but further work is needed to enroll previously diagnosed patients and to ensure rapid ART in key patient subgroups. Further research is needed on facility and geographic factors and on strategies for improving timely ART initiation among vulnerable subgroups.

Factors Influencing Rapid Antiretroviral Therapy Initiation at Four eThekwini Clinics, KwaZulu-Natal, South Africa

Timely uptake of Antiretroviral therapy considerably improves the health of people living with the Human Immunodeficiency virus. We conducted a cross-sectional study of newly HIV diagnosed individuals in four clinics in eThekwini municipality, KwaZulu-Natal. Data was collected between June 2020 and December 2020. Participants completed an interviewer-administered questionnaire after HIV testing, on the day of HIV diagnosis. We evaluated factors influencing uptake of same-day ART initiation in eThekwini clinics, KwaZulu Natal, South Africa. Demographic information, health status, sexual behaviour, knowledge of universal test and treat (UTT), ART initiation uptake, and disclosure data was collected. Among the 403 participants, same-day initiation (SDI) was 69.2% (n = 279). We observed the number of sexual partners (aOR 0.35; 95% CI 0.15–0.81), HIV status of the partner (aOR 5.03; 95% CI 2.74–9.26) and knowledge of UTT (aOR 1.97; 95% CI 1.34–2.90) were identified as major factors influencing uptake of same-day ART initiation. More strategies are needed to achieve the SDI uptake within the framework of UTT.