HIV Treatment Guidelines Research Articles

Role of Dolutegravir/Lamivudine in the Management of Pregnant People Living with HIV-1: A Narrative Review.

Lowering viral load during pregnancy is regarded as the most important method of reducing human immunodeficiency virus 1 (HIV-1) vertical transmission risk, and minimizing fetal exposure to drugs is a guiding principle during pregnancy. Dolutegravir/lamivudine (DTG/3TC) has demonstrated high efficacy, a high barrier to resistance, and a good safety profile in non-pregnant individuals; however, DTG/3TC is not recommended by perinatal HIV treatment guidelines for initial therapy in pregnant people living with HIV-1 because of limited data on use of the 2-drug regimen during pregnancy. Efficacy and pharmacokinetic data from pregnant individuals using DTG and/or 3TC are reviewed and used to extrapolate anticipated DTG/3TC efficacy in pregnancy. There are robust data on the use of DTG- and 3TC-containing combination regimens, which are recommended by perinatal HIV treatment guidelines during pregnancy, supporting their well-established efficacy and safety in pregnant people living with HIV-1. Updated data from the Tsepamo and Eswatini surveillance studies (>14,000 DTG exposures from conception) indicate no increased risk of neural tube defects with DTG. Pharmacokinetic data for DTG and 3TC indicate that exposures in pregnancy are within the therapeutically effective range seen in non-pregnant adults. Two studies evaluated DTG/3TC during pregnancy and both reported high virologic suppression rates [HIV-1 ribonucleic acid (RNA)<50 copies/mL at delivery: 97% (30/31) overall], no events of vertical transmission, and no new safety signals, consistent with the use of DTG-based 3-drug regimens in pregnancy. The use of DTG/3TC during pregnancy is anticipated to be comparably effective and well tolerated for both parental health and prevention of vertical transmission with fetal exposure to fewer antiretrovirals compared with 3- or 4-drug regimens. These considerations are relevant when evaluating use of DTG/3TC in people living with HIV-1 who are pregnant or considering pregnancy in clinical practice and in perinatal HIV treatment guidelines.Video abstract available for this article. Supplementary file1 (MP4 319,147 KB).

Healthcare resource utilization and related cost of non-HIV comorbidity management in people with HIV in a Spanish cohort from 2007-2016

Objective To estimate the cost and healthcare resource utilization (HRU) associated with the prevalence of comorbidities in people living with HIV (PLWH) in a Spanish cohort over ten years. Methods: Cohort study carried out at the HIV outpatient clinic of the University Hospital Virgen del Rocío based on data collected during 2007-2016. PLWH with at least one follow-up visit were included. Comorbidities were determined by examining diagnostic codes in the electronic medical records. Costs were estimated from hospitalizations, emergency and non-HIV visits, laboratory tests for conditions unrelated to HIV infection, HIV antiretroviral therapy, and other non-HIV diagnostic tests. A linear regression was performed with non-ART costs as the dependent variable and patient characteristics (sex, HIV transmission route, age, CD4, comorbidities, and infection duration) as independent variables. Results: The study included 2,798 PLWH; 83% were men with a mean age of 38.6 years. Overall, 52.5% of PLWH had at least one non-HIV comorbidity and 21.2% had ≥3 comorbidities. The most prevalent comorbidities were hepatitis C (25.3%) and hypertension (22.9%). The presence of comorbidities increased the total healthcare cost up to 80% in PLWH with ≥3 comorbidities compared with those without comorbidities (over a 10-year period (115,867.3€vs 64,290.7€, p < 0.001). The number of comorbidities was linked to higher healthcare costs in PLWH in the adjusted model. Conclusion: Comorbidities raised the total healthcare costs for PLWH, with a greater impact on those with multiple comorbidities compared to those with few or none. Both clinical and economic decision-makers must consider and assess the cost of comorbidities when evaluating HIV treatment guidelines or recommendations.

Improving HIV testing, linkage, and retention in care among South African men through U = U messaging: A study protocol for two sequential hybrid type 1 effectiveness-implementation randomized controlled trials.

Increasing HIV testing and treatment coverage among people living with HIV (PLHIV) is essential for achieving global HIV epidemic control. However, compared to women, cis-gender heterosexual men living with HIV are significantly less likely to know their HIV status, initiate anti-retroviral therapy (ART) and achieve viral suppression. This is particularly true in South Africa, where men are also at increased risk of mortality resulting from AIDS-related illnesses. While there is growing knowledge of Treatment as Prevention or the concept Undetectable = Untransmittable (U = U) among PLHIV in Western and high-income countries, the reach and penetration of the U = U message in sub-Saharan Africa remains limited, and few studies have evaluated the impact of accessible and relatable U = U messages on ART initiation and adherence. To address these gaps, rigorous evaluations of interventions that incorporate U = U messages are needed, especially among men in high prevalence settings. Building on our U = U messages that we previously developed for men using behavioral economics insights and a human-centered design, we will conduct two sequential hybrid type 1 effectiveness-implementation trials to evaluate the impact of U = U messages on men's uptake of community-based HIV testing and ART initiation (Trial 1), and retention in care and achievement of viral suppression (Trial 2). For trial 1, a cluster randomized trial will be implemented with HIV testing service site-days (each day at one testing site) randomized to U = U or standard-of-care (SoC) messages inviting men to test for HIV. For trial 2, an individual-level randomized control trial will be implemented, with men initiating ART at six government clinics randomized to receive U = U counselling or SoC treatment adherence messaging. We will incorporate a multi-method evaluation to inform future implementation of U = U messaging interventions. The study will be conducted in the Buffalo City Metro Health District of the Eastern Cape Province and in the Cape Town Metro Health District in the Western Cape Province in South Africa. These trials are the first to rigorously evaluate the impact of U = U messaging on HIV testing uptake, ART initiation and achievement of viral suppression among African men. If effective, these messaging interventions can shape global HIV testing, treatment and adherence counselling guidelines and practices.

"No One Needs to be Forced": Qualitative Insights on Competing Priorities between Antiretroviral Therapy and Reproductive Health Planning during the Dolutegravir Rollout.

Potential associations between periconception dolutegravir (DTG) exposure and neural tube defects (NTDs) reported in 2018 caused shifting international and national antiretroviral treatment (ART) guidelines. They sometimes required women to use contraception prior to initiating DTG. To better understand the tensions between ART and family planning (FP) choices, and explore the decision-making processes of women living with HIV (WLHIV) and their healthcare providers (HCPs) employed, we conducted interviews with WLHIV exposed to DTG and their providers in western Kenya from July 2019 to August 2020. For the interviews with WLHIV, we sampled women at varying ages who either continued using DTG, switched to a different ART, or became pregnant while using DTG. We utilized inductive coding and thematic analysis. We conducted 44 interviews with WLHIV and 10 with providers. We found four dominant themes: (1) a range of attitudes about birth defects, (2) nuanced knowledge of DTG and its potential risk of birth defects, (3) significant tensions at the intersection of DTG and FP use with varying priorities amongst WLHIV and their providers for navigating the tensions, and (4) WLHIV desiring autonomy, and provider support for this, in such decision-making. Variations in beliefs were noted between WLHIV and HCPs. WLHIV highlighted the impact of community and social beliefs when discussing their attitudes while HCPs generally reported more medicalized views towards DTG utilization, potential adverse outcomes, and FP selection. Decisions pertaining to ART and FP selection are complex, and HIV treatment guidelines need to better support women's agency and reproductive health justice.

Incidence density mortality rate among HIV-positive children on antiretroviral therapy in Ethiopia: a systematic review and meta-analysis.

BackgroundHuman Immunodeficiency Virus (HIV) continues to be the major cause of childhood deaths, particularly in the sub-Saharan African region. In Ethiopia, though several primary studies have been conducted on the incidence of HIV-related child mortality, the pooled incidence density mortality rate among HIV-positive children is unknown. Therefore, this systematic review and meta-analysis aimed to estimate the pooled incidence density mortality rate among HIV-positive children and identify its associated factors in Ethiopia.MethodsWe browsed PubMed, HINARI, Science Direct, Google Scholar, African Journals Online, and cross-references using different search terms to identify articles. Quality appraisal was done using the Joanna Briggs Institute checklist. Meta-package was used to estimate the pooled incidence of mortality and hazard ratio (HR) of predictors. Heterogeneity was tested using the I-square statistics. Publication bias was tested using a funnel plot visual inspection and Egger’s test. Data was presented using forest plots and tables. The random effect model was used to compute the pooled estimate.ResultsThe overall pooled incidence density mortality rate among HIV-positive children was 2.52 (95% CI: 1.82, 3.47) per 100 child years. Advanced HIV disease (hazard ratio (HR): 3.45, 95% CI (Confidence Interval): 2.64, 4.51), tuberculosis co-infection (HR: 3.19, 95% CI: 2.08, 4.88), stunting (3.22, 95% CI: 2.46, 4.22), underweight (HR: 2.71, 95% CI: 1.72, 4.26), wasting (HR: 4.14, 95% CI: 2.27, 7.58), didn’t receive Isoniazid preventive therapy (HR: 3.33, 95% CI: 2.22, 4.99), anemia (HR: 3.03, 95% CI: 2.52, 3.64), fair or poor antiretroviral therapy adherence (HR: 4.14, 95% CI: 3.28, 5.28) and didn’t receive cotrimoxazole preventive therapy (HR: 3.82, 95% CI: 2.49, 5.86) were factors associated with a higher hazard of HIV related child mortality.ConclusionsThe overall pooled incidence density mortality rate among HIV-positive children was high in Ethiopia as compared to the national strategy target. Therefore, counseling on antiretroviral therapy adherence should be strengthened. Regular monitoring of hemoglobin levels and assessment of nutritional status should be done for all children living with HIV. Moreover, healthcare professionals should follow the national HIV treatment guidelines and provide cotrimoxazole preventive therapy and Isoniazid preventive therapy up on the guidelines for children living with HIV.RegistrationRegistered in PROSPERO with ID: CRD42023486902.

High viral suppression rates among PLHIV on dolutegravir who had an initial episode of viral non-suppression in Uganda September 2020-July 2021.

In 2019, WHO recommended dolutegravir (DTG) as a backbone for first- and second-line antiretroviral therapy (ART) regimens for people living with HIV (PLHIV). According to the 2018 Uganda's HIV treatment guidelines, patients with viral non-suppression (≥1,000 copies/mL) should receive intensive adherence counseling (IAC) with repeat viral load (VL) within 6 months. This analysis focused on the prevalence and factors associated with viral suppression following IAC among PLHIV on DTG-based regimens (DBRs) with an initial episode of viral non-suppression (VNS) in Uganda. We conducted a retrospective analysis for PLHIV on DBRs with an initial episode of VNS (≥1,000 copies/mL) in Uganda during October 2019-September 2020 who had a follow up VL test result during September 2020-July 2021. Data were abstracted from the Central Public Health Laboratory (CPHL) database, including patient demographics and VL results. Viral non-suppression (VNS) was defined as a VL test result of ≥1,000 copies/mL. We characterized PLHIV on DBRs and used logistic regression models to determine factors associated with VL suppression after an initial episode of VNS. A total of 564 PLHIV on DBRs with an initial episode of VNS were followed up and 43 were excluded due to missing data. Of the 521, 220 (42.2%) were children (<15 years) and 231 (44.3%) were female. Median age was 28 years (interquartile range [IQR]: 12-43 years), and median duration on DBRs was 12 months (IQR: 6-15 months). Overall, 80.8% (421/521) PLHIV had a suppressed viral load at first follow up testing (children = 74.5% [164/220]; adults = 85.4% [257/301]). Children with initial VL results ≥5,000 copies/mL were less likely to achieve viral suppression at follow up testing compared to those with <5,000 copies/mL (AOR: 0.38; 95% CI: 0.20-0.71; p = 0.002). In a programmatic setting, most adults and children suppressed following an initial episode of VNS on DBRs. High rates of suppression after VNS suggest adherence challenges, rather than drug resistance. Continuation of DBRs should be considered before regimen switch.

Clinical Decision Support System for Guidelines-Based Treatment of Gonococcal Infections, Screening for HIV, and Prescription of Pre-Exposure Prophylaxis: Design and Implementation Study.

The syndemic nature of gonococcal infections and HIV provides an opportunity to develop a synergistic intervention tool that could address the need for adequate treatment for gonorrhea, screen for HIV infections, and offer pre-exposure prophylaxis (PrEP) for persons who meet the criteria. By leveraging information available on electronic health records, a clinical decision support (CDS) system tool could fulfill this need and improve adherence to Centers for Disease Control and Prevention (CDC) treatment and screening guidelines for gonorrhea, HIV, and PrEP. The goal of this study was to translate portions of CDC treatment guidelines for gonorrhea and relevant portions of HIV screening and prescribing PrEP that stem from a diagnosis of gonorrhea as an electronic health record-based CDS intervention. We also assessed whether this CDS solution worked in real-world clinic. We developed 4 tools for this CDS intervention: a form for capturing sexual history information (SmartForm), rule-based alerts (best practice advisory), an enhanced sexually transmitted infection (STI) order set (SmartSet), and a documentation template (SmartText). A mixed methods pre-post design was used to measure the feasibility, use, and usability of the CDS solution. The study period was 12 weeks with a baseline patient sample of 12 weeks immediately prior to the intervention period for comparison. While the entire clinic had access to the CDS solution, we focused on a subset of clinicians who frequently engage in the screening and treatment of STIs within the clinical site under the name "X-Clinic." We measured the use of the CDS solution within the population of patients who had either a confirmed gonococcal infection or an STI-related chief complaint. We conducted 4 midpoint surveys and 3 key informant interviews to quantify perception and impact of the CDS solution and solicit suggestions for potential future enhancements. The findings from qualitative data were determined using a combination of explorative and comparative analysis. Statistical analysis was conducted to compare the differences between patient populations in the baseline and intervention periods. Within the X-Clinic, the CDS alerted clinicians (as a best practice advisory) in one-tenth (348/3451, 10.08%) of clinical encounters. These 348 encounters represented 300 patients; SmartForms were opened for half of these patients (157/300, 52.33%) and was completed for most for them (147/300, 89.81%). STI test orders (SmartSet) were initiated by clinical providers in half of those patients (162/300, 54%). HIV screening was performed during about half of those patient encounters (191/348, 54.89%). We successfully built and implemented multiple CDC treatment and screening guidelines into a single cohesive CDS solution. The CDS solution was integrated into the clinical workflow and had a high rate of use.

Long-term HIV care outcomes under universal HIV treatment guidelines: A retrospective cohort study in 25 countries.

While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with ≥12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality.

The impact ofshifts inPEPFAR funding policy onHIV services inEastern Uganda (2015-21).

Although donor transitions from HIV programmes are increasingly common in low-and middle-income countries, there are limited analyses of long-term impacts on HIV services. We examined the impact of changes in President's Emergency Plan for AIDS Relief (PEPFAR) funding policy on HIV services in Eastern Uganda between 2015 and 2021.We conducted a qualitative case study of two districts in Eastern Uganda (Luuka and Bulambuli), which were affected by shifts in PEPFAR funding policy. In-depth interviews were conducted with PEPFAR officials at national and sub-national levels (n = 46) as well as with district health officers (n = 8). Data were collected between May and November 2017 (Round 1) and February and June 2022 (Round 2). We identified four significant donor policy transition milestones: (1) between 2015 and 2017, site-level support was withdrawn from 241 facilities following the categorization of case study districts as having a 'low HIV burden'. Following the implementation of this policy, participants perceived a decline in the quality of HIV services and more frequent commodity stock-outs. (2) From 2018 to 2020, HIV clinic managers in transitioned districts reported drastic drops in investments in HIV programming, resulting in increased patient attrition, declining viral load suppression rates and increased reports of patient deaths. (3) District officials reported a resumption of site-level PEPFAR support in October 2020 with stringent targets to reverse declines in HIV indicators. However, PEPFAR declared less HIV-specific funding. (4) In December 2021, district health officers reported shifts by PEPFAR of routing aid away from international to local implementing partner organizations. We found that, unlike districts that retained PEPFAR support, the transitioned districts (Luuka and Bulambuli) fell behind the rest of the country in implementing changes to the national HIV treatment guidelines adopted between 2017 and 2020. Our study highlights the heavy dependence on PEPFAR and the need for increasing domestic financial responsibility for the national HIV response.

Standard of care in advanced HIV disease: review of HIV treatment guidelines in six sub-Saharan African countries

BackgroundThe World Health Organization (WHO) recommends an evidence-based package of care to reduce mortality and morbidity among people with advanced HIV disease (AHD). Adoption of these recommendations by national guidelines in sub-Saharan Africa is poorly documented. We aimed to review national guidelines for AHD management across six selected countries in sub-Saharan Africa for benchmarking against the 2021 WHO recommendations.MethodsWe reviewed national guidelines from six countries participating in an ongoing randomized controlled trial recruiting people with AHD. We extracted information addressing 18 items of AHD diagnosis and management across the following domains: [1] Definition of AHD, [2] Screening, [3] Prophylaxis, [4] Supportive care, and [5] HIV treatment. Data from national guideline documents were compared to the 2021 WHO consolidated guidelines on HIV and an agreement score was produced to evaluate extent of guideline adoption.ResultsThe distribution of categories of agreement varied for the national documents. Four of the six countries addressed all 18 items (Malawi, Nigeria, Sierra Leone, Uganda). Overall agreement with the WHO 2021 guidelines ranged from 9 to 15.5 out of 18 possible points: Malawi 15.5 points, Nigeria, and Sierra Leone 14.5 points, South Africa 13.5 points, Uganda 13.0 points and Botswana with 9.0 points. Most inconsistencies were reported for the delay of antiretroviral therapy (ART) in presence of opportunistic diseases. None of the six national guidelines aligned with WHO recommendations around ART timing in patients with tuberculosis. Agreement correlated with the year of publication of the national guideline.ConclusionNational guidelines addressing the care of advanced HIV disease in sub-Saharan Africa are available. Besides optimal timing for start of ART in presence of tuberculosis, most national recommendations are in line with the 2021 WHO standards.

Near-universal same-day linkage to ART care among newly diagnosed adults living with HIV: A cross-sectional study from primary health facilities, in urban Malawi.

Malawi HIV treatment guidelines recommend same-day antiretroviral therapy (ART) initiation. Overall 97.9% of Malawians living with HIV (PLHIV) are on ART, same-day ART initiation prevalence and factors that facilitate it have not been fully described. We assessed same-day ART initiation and described individual, health system and health facility infrastructural factors at health facilities supported by expert clients (EC). ECs are lay PLHIV who support other PLHIV. The study was conducted in urban and semi-urban primary health facilities, in Blantyre, Malawi. It was a cross-sectional, descriptive survey of PLHIV and health facility leaders. Eligibility criteria included age ≥ 18 years, new diagnosis of HIV, received counselling from ECs, and offered same-day ART. The study was conducted from December 2018 to June 2021, and 321 study participants enrolled. Mean age (standard deviation) was 33 years (10) with 59% females. In total, 315 (98.1%) initiated same-day ART. Four participants did not because of mental unpreparedness, one wanted to try herbal medicine and one was concerned about stigma related to taking ART. Participants reported health facility accessibility (99%, 318/321), privacy (91%, 292/321) and quality of counselling by EC as excellent (40%, 128/321). Same-day ART was nearly universal. Participants' satisfaction with health services delivery, the presence of EC, and infrastructural characteristics such as adequate privacy were cited as reasons favoring same-day linkage to ART. The most cited reason for not starting same-day ART was mental unpreparedness.

Exploring barriers to switching "on time" to second-line antiretroviral therapy among nurses in primary health care facilities, Ekurhuleni Health District, South Africa.

Ensuring that all HIV-infected people receive antiretroviral therapy (ART) and achieve viral suppression are key South African strategies to end the AIDS epidemic in the country. National HIV treatment guidelines recommend an immediate switch to second-line ART following virological failure with first-line ART. Nurses based in district health facilities are at the forefront of implementing this recommendation. While there are often delays in switching and in some instances no switch, the reasons for and barriers to delayed switching are not well understood at the primary care level. To explore the views of frontline nursing staff about factors contributing to delayed switching of patients who have failed first-line ART regimen in Ekurhuleni district, South Africa. A qualitative study was conducted among 21 purposively sampled nurses who provide HIV treatment and care to patients in 12 primary health care (PHC) facilities in Ekurhuleni Health District, Gauteng Province, South Africa. Individual in-depth interviews explored nurses' experiences regarding their recognition of virological failure and understanding of "on time" switching to second-line ART. Interviews probed the circumstances contributing to delays in switching. After digital audio recording and transcription, manual inductive thematic analysis was used to analyse the data. Multiple barriers were identified: 1) Healthcare provider factors included a lack of knowledge and confidence coupled with demotivation in the workplace; 2) Patient issues similarly comprised a lack of knowledge as well as resistance to being switched to another drug regimen and loss to follow up; 3) Systems factors were poor facility leadership, shortages of medication, staffing constraints, and the inability to trace laboratory results, especially for migrant patients. Reasons for delayed switching of patients to second-line ART are multifactorial and require integrated interventions at health provider, patient and health system levels.

Effect of UTT on viral suppression and ART adherence

With strong evidence of the health and prevention benefits of early treatment, WHO revised its HIV treatment guidelines in 2015 and recommended that all people living with HIV start antiretroviral therapy (ART) irrespective of CD4 cell count or disease stage.1 This recommendation resulted in dramatic changes to HIV programmes in resource-limited settings and the scale-up of ART programmes in Africa. However, there was initial concern and mixed evidence in the literature that early treatment, especially for people living with HIV who are asymptomatic, could lead to lower rates of adherence and subsequent viral suppression and poor retention.

Pre-treatment HIV-1 drug resistance in antiretroviral therapy-naive adults in Eastern Africa: a systematic review and meta-analysis.

Pre-treatment HIV drug resistance (PDR) may result in increased risk of virological failure and acquisition of new resistance mutations. With recently increasing ART coverage and periodic modifications of the guidelines for HIV treatment, there is a need for an updated systematic review to assess the levels of the PDR among adults newly initiating ART in Eastern Africa. We conducted a systematic search for studies published between 1 January 2017 and 30 April 2022 in the MEDLINE Complete and CINAHL Complete, searched simultaneously using EBSCOhost, and Web of Science. To determine the overall PDR prevalence estimates, we extracted data from eligible articles and analysed prevalence estimates using Stata 14.2. A total of 22 eligible observation studies were selected. The studies included a total of 5852 ART-naive people living with HIV. The overall pooled prevalence of PDR was 10.0% (95% CI: 7.9%-12.0%, I2 = 88.9%) and 9.4% (95% CI: 7.0%-11.9%, I2 = 90.4%) for NNRTIs, 2.6% (95% CI: 1.8%-3.4%, I2 = 69.2%) for NRTIs and 0.7% (95% CI: 0.3%-1.2%, I2 = 29.0%) for PIs. No major integrase strand transfer inhibitors (INSTI)-related mutations were identified. We observed a moderate overall PDR prevalence among new ART initiators in this study. PDR to NNRTIs is more prevalent, underscoring the importance of the current WHO recommendation for replacement of NNRTIs by INSTIs. PDR to NRTIs was low but notable, which warrants continuous surveillance of pre-existing resistance to the dolutegravir co-administered NRTI in Eastern Africa.

Trends in Use of Combination Antiretroviral Therapy and Treatment Response from 2000 to 2016 in the Canadian Observational Cohort (CANOC): A Longitudinal Cohort Study.

Advances in treatment have turned HIV from a terminal illness to a more manageable condition. Over the past 20 years, there have been considerable changes to HIV treatment guidelines, including changes in preferred antiretrovirals and timing of initiation of combination antiretroviral therapy (cART). To examine real-world trends in cART utilization, viral control, and immune reconstitution among people living with HIV in Canada. Data were obtained from the Canadian Observational Cohort (CANOC). CANOC participants were eligible if they were antiretroviral therapy-naive at entry and initiated 3 or more antiretrovirals on or after January 1, 2000; if they were at least 18 years of age at treatment initiation; if they were residing in Canada; and if they had at least 1 viral load determination and CD4 count within 1 year of CANOC entry. Baseline and annual mean CD4 counts were categorized as less than 200, 200-350, 351-500, and more than 500 cells/mm3. Annual mean viral loads were reported as suppressed (< 50 copies/mL), low (50-199 copies/mL), or high detectable (≥ 200 copies/mL). The cART regimens were reported yearly. All CANOC participants were included (n = 13 040). Over the study period, the proportion of individuals with an annual mean CD4 count above 500 cells/mm3 increased from 16.3% to 65.8%, while the proportion of individuals with an undetectable mean viral load increased from 10.6% to 83.2%. As of 2007, the most commonly prescribed 2-agent nucleoside reverse transcriptase inhibitor backbone was tenofovir disoproxil fumarate and emtricitabine. In terms of third agents, non-nucleoside reverse transcriptase inhibitors were the most common class in the periods 2000-2003 and 2014-2015, protease inhibitors were most common in the period 2004-2013, and integrase inhibitors were most common in 2016. Concordance with treatment guidelines was demonstrated over time with respect to cART prescribing and immunologic and virologic response.

HIV treatment with dolutegravir and doravirine: rationale for selection and clinical outcomes in a highly treatment experienced population.

Dolutegravir and doravirine are individually safe and effective antiretroviral therapy (ART) components, but their combined use has not been studied in clinical trials and is not recommended in HIV treatment guidelines. We noted persons with HIV (PWH) receiving dolutegravir with doravirine at our Washington, DC, infectious disease clinic and undertook a service evaluation to understand why providers selected this ART, whether HIV virologic suppression was achieved and identify adverse effects of concomitant use. Case registry and prescriptions data identified 21 PWH receiving concomitant dolutegravir and doravirine with mean follow-up 576.1days (range 413-751); frequent reasons for switching were multiple ART resistance (57.1%), proton pump inhibitor usage (28.6%) and renal failure (28.6%), with 52.4% switched from protease inhibitor or cobicistat-boosted regimens. Dolutegravir with doravirine alone was prescribed for 60%, and additional ART in 40%. During 12 months follow-up mean CD4 was 585.9 (baseline 570.7) with undetectable viral load in 77.8% (baseline 66.7%). No discontinuations for drug-related adverse events or virologic failure occurred. Dolutegravir with doravirine was well tolerated in small numbers of highly treatment experienced PWH at our clinic, achieving virologic suppression in most. Establishing the efficacy and safety of dolutegravir with doravirine for HIV treatment in randomized trials remains important.

Toward Ending the HIV Epidemic: Temporal Trends and Disparities in Early ART Initiation and Early Viral Suppression Among People Newly Entering HIV Care in the United States, 2012-2018.

In 2012, the US Department of Health and Human Services updated their HIV treatment guidelines to recommend antiretroviral therapy (ART) for all people with HIV (PWH) regardless of CD4 count. We investigated recent trends and disparities in early receipt of ART prescription and subsequent viral suppression (VS). We examined data from ART-naïve PWH newly presenting to HIV care at 13 North American AIDS Cohort Collaboration on Research and Design clinical cohorts in the United States during 2012-2018. We calculated the cumulative incidence of early ART (within 30 days of entry into care) and early VS (within 6 months of ART initiation) using the Kaplan-Meier survival function. Discrete time-to-event models were fit to estimate unadjusted and adjusted associations of early ART and VS with sociodemographic and clinical factors. Among 11 853 eligible ART-naïve PWH, the cumulative incidence of early ART increased from 42% in 2012 to 82% in 2018. The cumulative incidence of early VS among the 8613 PWH who initiated ART increased from 83% in 2012 to 93% in 2018. In multivariable models, factors independently associated with delayed ART and VS included non-Hispanic/Latino Black race, residence in the South census region, being a male with injection drug use acquisition risk, and history of substance use disorder (SUD; all P ≤ .05). Early ART initiation and VS have substantially improved in the United States since the release of universal treatment guidelines. Disparities by factors related to social determinants of health and SUD demand focused attention on and services for some subpopulations.

Drug use stigma, antiretroviral therapy use, and HIV viral suppression in a community-based sample of people with HIV who inject drugs.

To examine the association of drug use stigma with antiretroviral therapy (ART) use and HIV viral suppression among people with HIV who inject drugs in India. Cross-sectional biobehavioral survey. Between August 2016 and May 2017, persons aged at least 18 years who reported injection drug use in the past 2 years were recruited via respondent-driven sampling (RDS) in 12 Indian cities (approximately 1000 per city). The analysis was restricted to participants with laboratory-confirmed HIV infection who self-reported a prior HIV diagnosis and were eligible for ART per concurrent national HIV treatment guidelines. Enacted and internalized drug use stigma were each measured by five to six-item subscales. The study outcomes were HIV viral suppression (<150 copies/ml) and self-reported past 30-day ART use. RDS-II weighted multivariable logistic regression with a city-level random-intercept was used to estimate adjusted odds ratios (aOR) and corresponding 95% confidence intervals (CIs). Among 971 ART-eligible participants previously diagnosed with HIV, 65.1% reported ART use and 56.1% were virally suppressed. Reporting any enacted stigma (vs. none) was associated with lower odds of ART use [aOR = 0.26 (95% CI = 0.15-0.44)] and viral suppression [aOR = 0.49 (95% CI = 0.31-0.78)]. High internalized stigma scores (>median vs. ≤median) were associated with lower odds of viral suppression among participants aged at least 35 years [aOR = 0.51 (95% CI = 0.27-0.97)] but not among participants aged less than 35 years [aOR = 1.22 (95% CI = 0.57-2.60)]. Similar associations were observed in analyses restricted to participants ever linked to HIV care. Drug use stigma may be a barrier to HIV viral suppression among people with HIV who inject drugs, thereby hindering efforts to achieve HIV control.

Prescribing patterns of antiretroviral treatments during pregnancy for women living with HIV in Canada 2004-2020: A surveillance study.

While treatment guidelines for HIV in adults have evolved rapidly with the advent of new antiretroviral (ARV) treatment, those for the prevention of vertical HIV transmission in pregnancy have evolved more slowly due to safety and efficacy concerns. Here we describe Canadian prescribing patterns for ARV treatments during pregnancy and compare them to perinatal HIV prescribing guidelines of the United States Department of Health and Human Services (HHS), that are commonly used in Canada and include recommendations for newly commercialized therapies. The Canadian Perinatal HIV Surveillance Program (CPHSP) captures annual medical data on mothers living with HIV and their infants from 23 sites across Canada. Women from this cohort who received an ARV treatment during pregnancy and who gave birth between 2004 and 2020 were included in the study. ARV treatments were designated as 'preferred/alternative' as per HHS HIV perinatal guidelines, or 'other than preferred/alternative'. We identified 3673 pregnancies from 2720 women. The proportion of women that conceived while on ARV treatment increased from 29% in 2003 to 90% in 2020. Other than preferred/alternative ARV treatments were received in 1112 (30%) of pregnancies and this was significantly associated with having initiated ARV treatment before conception. In Canada during the study period, a high number of women were prescribed an other than preferred/alternative ARV treatment during pregnancy. Further optimization of ARV treatment in women of childbearing age living with HIV is warranted.

Immunological and virological outcomes in children on lamivudine monotherapy: A South African public sector experience

Background. In resource-limited settings, holding regimens such as lamivudine monotherapy (LAM) have been used to manage HIV-positive children failing combination antiretroviral therapy to mitigate the risk of drug resistance developing, while adherence barriers are addressed or when access to second- or third-line regimens is restricted. South African HIV treatment guidelines previously advocated the use of LAM to manage HIV-infected children with virological failure. However, the outcomes of patients on LAM compared with those who continued on a failing regimen have not been well described. Objectives. To investigate characteristics of a large cohort of children placed on LAM and their outcomes. Methods. This was a retrospective review of children with virological failure and the documented M184V drug resistance mutation who were placed on LAM v. a control group of children who continued on a failing regimen despite persistent virological failure. Virological and immunological outcomes of LAM were compared with those in patients who remained on a failing regimen. Results. A total of 179 children were included in the analysis, with 92 in the LAM group and 87 in the control group. The median (interquartile range (IQR)) age at baseline was 9.2 (5.4 - 12) years, the median CD4 count was 384 (184 - 622) cells/μL, and the median HIV viral load was 4.7 (IQR 3.7 - 5.3) log10. Twenty-two children (25.6%) in the LAM group and 15 (17.4%) in the control group experienced immunological deterioration. There was no statistical difference between the two groups with regard to overall time to immunological deterioration (log-rank p-value 0.4810). Conclusion. Given that a higher proportion of children in the LAM group experienced immunological failure, the LAM strategy may be a useful short-term one but should be restricted to children with limited treatment options. Managing children with virological failure will continue to be a challenge until improved adherence strategies are available.