Adherence to antiretroviral therapy and the associated factors among people living with HIV/AIDS in Northern Peru: a cross-sectional study.

BACKGROUND: There are approximately 72,000 people living with HIV/AIDS (PLHIV) in Peru. Non-adherence to antiretroviral therapy (ART) is the most important factor for therapeutic failure and the development of resistance. Peru has achieved moderate progress in meeting the 90-90-90 targets, but only 60% of PLHIV receiving ART are virally suppressed. The purpose of this study was to understand ART adherence in the Peruvian context, including developing sociodemographic and clinical profiles, evaluating the clinical management strategies, and analyzing the relationships between the variables and adherence of PLHIV managed at a regional HIV clinic in Lambayeque Province (Northern Peru). METHODS: This was a cross-sectional study with 180 PLHIV adults, non-randomly but consecutively selected with self-reported ART compliance (78.2% of the eligible population). The PLHIV profile (PLHIV-Pro) and the Simplified Medication Adherence Questionnaire (SMAQ) were used to collect sociodemographic information, clinical variables, and data specific to ART adherence. Descriptive analysis of sociodemographic and clinical characteristics was performed. Bivariate analysis was performed with the Mann-Whitney test, Chi square test, and Yates correction. RESULTS: The 180 PLHIV sample included 78.9% men, 49.4% heterosexual, 45% with a detectable HIV-1 viral load less than 40 copies/ml, 58.3% not consistently adherent, and only 26.1% receiving Tenofovir + Lamivudine + Efavirenz. Risk factors significant for non-adherence included concurrent tuberculosis, discomfort with the ART regime, and previous pauses in ART. Multivariate analysis of nested models indicated having children is a protector factor for adherence. CONCLUSIONS: Self-reported adherence appeared to be low and the use of first-line therapy is not being prescribed homogeneously. Factors associated with nonadherence are both medical and behavioral, such as having tuberculosis, pausing ART, or experiencing discomfort with ART. The Peruvian government needs to update national technical standards, monitor medication availability, and provide education to health care professionals in alignment with evidence-based guidelines and international recommendations. Instruments to measure adherence need to be developed and evaluated for use in Latin America.

Changes in serum phosphate and potassium and their effects on mortality in malnourished African HIV-infected adults starting antiretroviral therapy and given vitamins and minerals in lipid-based nutritional supplements: secondary analysis from the Nutritional Support for African Adults Starting Antiretroviral Therapy (NUSTART) trial.

Malnourished HIV-infected patients starting antiretroviral therapy (ART) are at high risk of early mortality, some of which may be attributed to altered electrolyte metabolism. We used data from a randomised controlled trial of electrolyte-enriched lipid-based nutritional supplements to assess the association of baseline and time-varying serum phosphate and K concentrations with mortality within the first 12 weeks after starting ART. Baseline phosphate results were available from 1764 patients and there were 9096 subsequent serum phosphate measurements, a median of 6 per patient. For serum K there were 1701 baseline and 8773 subsequent measures, a median of 6 per patient. Abnormally high or low serum phosphate was more common than high or low serum K. Controlling for other factors found to affect mortality in this cohort, low phosphate which had not changed from the previous time interval was associated with increased mortality; the same was not true for high phosphate or for high or low K. Both increases and decreases in serum electrolytes from the previous time interval were generally associated with increased mortality, particularly in the electrolyte-supplemented group. The results suggest that changes in serum electrolytes, largely irrespective of the starting point and the direction of change, were more strongly associated with mortality than were absolute electrolyte levels. Although K and phosphate are required for tissue deposition during recovery from malnutrition, further studies are needed to determine whether specific supplements exacerbate physiologically adverse shifts in electrolyte levels during nutritional rehabilitation of ill malnourished HIV patients.

Virologic outcomes of antiretroviral therapy in patients with HIV-1 following bariatric surgery: A case series and review of the literature.

BACKGROUND: Selection of an antiretroviral regimen for people living with HIV (PLWH) involves various clinical considerations, such as comorbidities, archived drug resistance mutations, concomitant medications, and potential drug interactions and side effects. Alterations in the surface area and pH of the gastrointestinal tract following bariatric surgery may alter absorption, antiretroviral pharmacokinetics and viral suppression. Data on the efficacy of antiretroviral (ARV) therapy in PLWH who have undergone bariatric surgery are limited or lacking for new antiretrovirals, such as dolutegravir and bictegravir. METHODS: This case series reports virologic outcomes and side effects in eight cases of PLWH receiving ARV therapy who underwent bariatric surgery. A systematic literature review was performed to review the available literature on the efficacy and safety of antiretroviral regimens in PLWH who have undergone bariatric surgery. RESULTS: Virologic suppression was not impacted for obese PLWH who underwent bariatric surgery following failure of life-style modifications and pharmacological therapy. CONCLUSIONS: There were no deleterious effects on HIV progression for PLWH that underwent bariatric surgery. More prospective research is required to validate the effects of bariatric surgery on immunologic and virologic function outcomes. Close involvement of HIV and surgical specialists is recommended to manage ARV therapy in patients undergoing bariatric surgery.

HIV seroconversion and associated factors among seronegative pregnant women attending ANC in Ethiopia: an institution-based cross-sectional study.

Background: In countries with limited resources, including Ethiopia, HIV is diagnosed using a rapid serological test, which does not detect the infection during the window period. Pregnant women who test negative for HIV on the first test may seroconvert throughout pregnancy. Women who are seroconverted during pregnancy may not have received interventions, as they are considered HIV-negative unless they are retested for HIV at the end of their pregnancy. Due to limited data on HIV seroconversion, this study aimed to measure the extent of HIV seroconversion and to identify associated factors among seronegative pregnant women attending ANC in Ethiopia. Methods: Institution-based cross-sectional study was conducted among HIV-negative pregnant women attending the ANC in Ethiopia between June and July 2020. Socio-demographic, clinical, and behavioral data were collected through face-to-face questionnaires and participants' records review. HIV retesting was performed to determine the current HIV status of pregnant women. The data collected were entered into Epi data version 4.4.1 and were exported and analyzed by SPSS version 25. A p-value < 0.25 in the bivariate analysis was entered into multivariable logistic regression analysis and a p-value of < 0.05 was considered statistically significant. Result: Of the 494 pregnant women who tested negative for HIV on their first ANC test, six (1.2%) tested positive on repeat testing. Upon multivariable logistic regression, pregnant women who have had a reported history of sexually transmitted infections [AOR = 7.98; 95% CI (1.21, 52.82)], participants' partners reported travel history for work frequently [AOR = 6.00; 95% CI (1.09, 32.99)], and sexually abused pregnant women [AOR = 7.82; 95% CI (1.194, 51.24)] were significantly associated with HIV seroconversion. Conclusion: The seroconversion rate in this study indicates that pregnant women who are HIV-negative in early pregnancy are at an ongoing risk of seroconversion throughout their pregnancy. Thus, this study highlights the benefit of a repeat HIV testing strategy in late pregnancy, particularly when the risk of seroconversion or new infection cannot be convincingly excluded. Therefore, repeated testing of HIV-negative pregnant women in late pregnancy provides an opportunity to detect seroconverted pregnant women to enable the timely use of ART to prevent mother-to-child transmission of HIV infection.

Diabetes mellitus care cascade among a cohort of persons living with HIV and hypertension in Uganda: A retrospective cohort study.

BACKGROUND: In Uganda, it is recommended that persons with HIV receive integrated care to address both hypertension and diabetes. However, the extent to which appropriate diabetes care is delivered remains unknown and was the aim of this study. METHODS: We conducted a retrospective study among participants receiving integrated care for HIV and hypertension for at least 1 year at a large urban HIV clinic in Mulago, Uganda to determine the diabetes care cascade. RESULTS: Of the 1115 participants, the majority were female (n = 697, 62.5%) with a median age of 50 years (Inter Quartile Range: 43, 56). Six hundred twenty-seven participants (56%) were screened for diabetes mellitus, 100 (16%) were diagnosed and almost all that were diagnosed (n = 94, 94%) were initiated on treatment. Eighty-five patients (90%) were retained and all were monitored (100%) in care. Thirty-two patients (32/85, 38%) had glycaemic control. Patients on a Dolutegravir-based regimen (OR = 0.31, 95% CI = 0.22-0.46, p < 0.001) and those with a non-suppressed viral load (OR = 0.24, 95% CI = 0.07-0.83, p = 0.02) were less likely to be screened for diabetes mellitus. CONCLUSIONS: In very successful HIV care programs, large gaps still linger for the management of non-communicable diseases necessitating uniquely designed intervention by local authorities and implementing partners addressing the dual HIV and non-communicable diseases burden.

Seroconversion, seroreversion, and serowaffling among participants initiating antiretroviral therapy in Project DETECT.

BACKGROUND: Incomplete HIV seroconversion and seroreversion are increasingly documented by testing and pre-exposure prophylaxis programs more than previously recognized. This analysis reports on incomplete seroconversion and seroreversion by specimen and test type among Project DETECT participants. METHODS: Project DETECT included a longitudinal study of point-of-care tests. Participants were categorized as having "incomplete seroconversion" if all timepoints had ≥1 nonreactive test at study censoring. Among participants with incomplete seroconversion, we defined "seroreversion" as sustained regression to nonreactive for any test following a reactive result. We define "serowaffling" as any reactive result followed by a nonreactive and then reactive result. We used Fisher's exact tests to explore relationships between Fiebig stage at ART initiation and incomplete seroconversion, seroreversion, and serowaffling. RESULTS: Twenty of 1940 Project DETECT participants met criteria for this subset. Ten participants had complete seroconversion after a median of 23 (IQR 16-47) days following initial positive tests. Ten participants had incomplete seroconversion, eight of whom had seroreversion. Incomplete seroconversion with persistent nonreactive tests was seen only with oral fluid (OF). Of eight participants with seroreversion, all experienced seroreversion of OF tests if the test was ever reactive (n = 6); seroreversion occurred in fingerstick and venipuncture tests in two participants. Serowaffling occurred in nine (45%) participants. No associations were seen between Fiebig stage at ART start and complete seroconversion, seroregression, or serowaffling in our sample. CONCLUSIONS: OF tests may be particularly susceptible to providing false-negative results. Seroreversion and incomplete seroconversion among individuals on antiretroviral treatment may represent a growing problem for HIV testing and treatment programs.

First study of genital HPV infection among women living with HIV recruited from May to September 2018 in Eastern Algeria.

BACKGROUND: Genital HPV infection is recognized worldwide as one of the most common, if not the most common, sexually transmitted infection. Several studies have shown a higher prevalence of HPV infection in women living with HIV (WLWH). We aimed to determine the prevalence of HPV, the circulating genotypes, and its association with risk factors among Algerian WLHIV. METHODS: Cervical specimens were collected from 100 WLHIV. The detection of HPV infection was performed by Roche Linear Array test. RESULTS: The overall prevalence of HPV infection was determined at 32%, all including high risk HPV (HR-HPV). We found a great diversity of HR-HPV genotypes, the most common individually were HPV52, HPV16, HPV18 and HPV58, The highest prevalence was found in groups of genotype 52, 25%. HPV16 and 18 were less common (16%). Cervical cytology was abnormal in 66% (81.3% in the HPV + population), with a predominance of inflammatory lesions (75% HPV +), The most important determining risk factor for HPV infection in this series was a low CD4 T cell count <200/mm3 found in 72% of the HPV positive participants. CONCLUSION: Our study is an initial database, to be completed by a multicenter study to determine the most frequent genotypes in Algerian WLHIV, in order to discuss the introduction of the vaccine against HPV in Algeria, especially among WLHIV.

Tenofovir use is associated with a decreased risk of hepatocellular carcinoma among men with HIV irrespective of coinfection status.

Background & Aims: Tenofovir is recommended as part of the first-line antiretroviral therapy (ART) to treat people living with HIV (PLWH) with HBV coinfection. However, the effects of tenofovir-containing ART on hepatocellular carcinoma (HCC) risk among PLWH with/without chronic hepatitis virus infections remain unclear. Methods: This study included 23,838 PLWH. All of them were males aged ≥20 years and followed prospectively during 2000-2017. Four major nationwide registries - the Human Immunodeficiency Virus surveillance database, Taiwan Cancer Registry, Death Certification System, and National Health Insurance Database - were applied to define ART and comorbidities and ascertain newly diagnosed HCC. Tenofovir-containing ART was identified through prescription records. Cox proportional hazards models were used to determine the association of tenofovir use with HCC incidence. Results: HCC incidence was lower among ever users of tenofovir than among never users (24.2 and 85.7 per 100,000 person-years, respectively). Ever users had significantly reduced HCC risk (adjusted hazard ratio 0.20, 95% CI 0.13-0.31). The effect of tenofovir use on reduced risk for HCC consistently favored never users across many prespecified subgroups, including HBV or HCV coinfection (p <0.05). The findings were consistent in subgroups of PLWH diagnosed with HIV before tenofovir's approval and in those born before the nationwide roll-out of neonatal HBV vaccination. Conclusions: Our findings underscore the need for randomized controlled trials of tenofovir in combination with long-acting injectable ART regimens to assess its safety and efficacy in PLWH, particularly in those with HBV or HCV coinfection. Impact and implications: Tenofovir's effect on the risk of hepatocellular carcinoma (HCC) among people living with HIV with hepatitis B or C coinfection remains under investigated. This nationwide prospective cohort study, comprising 23,838 men living with HIV, showed that tenofovir-containing antiretroviral therapy was associated with reduced risk of HCC (adjusted relative risk: 0.20, 95% CI 0.13-0.31), which was consistently observed across many prespecified subgroups. The effect of tenofovir use on HCC risk should be further investigated in PLWH, particularly following the development of long-acting injectable ART regimens.

Determinates of anemia among Human Immune Deficiency Virus positive children on Anti-retro Viral Therapy in selected health facilities, Northwest Ethiopia: A Case-Control Study.

Even though antiretroviral therapy (ART) access for human immunodeficiency virus (HIV)-infected children increased dramatically, anaemia has continued as a challenge regardless of a cluster of differentiation (CD4) count and viral load. Hence, the present study aimed to assess the determinants of iron deficiency anaemia among children living with HIV after the initiation of ART. An institution-based unmatched case-control study was conducted among consecutively selected 712 children on HIV care from 1 September to 30 October 2022 in the Metekel zone. A pre-tested and structured data extraction checklist was used to collect the data. Data were analysed using STATA version 16 software. Binary logistic regression was used to find the association between independent variables and anaemia. The level of statistical significance was declared at a value of P < 0⋅05. A total of 712 HIV-positive children (178 cases and 534 controls) were included in this study, with a completeness rate of 98⋅8 %. In multivariable analysis, variables that have a statistically significant association with anaemia were as follows: CD4 count <350 (Adjusted Odds Ratio [AOR] 2⋅76; 95 % CI 1⋅76, 4⋅34), World Health Organization (WHO) clinical stage III (AOR 7⋅9; 95 % CI 3⋅5, 17⋅91) and stage IV (AOR 7⋅8; 95 % CI 3⋅37, 18⋅1), cotrimoxazole prophylaxis therapy (AOR 0⋅5; 95 % CI 0⋅31, 0⋅8) and mid-upper arm circumference (MUAC) ≤11⋅5 mm (AOR 2⋅1; 95 % CI 1⋅34, 3⋅28). The present study found that CD4 count, WHO clinical stage, cotrimoxazole prophylaxis therapy and MUAC were significantly associated with anaemia in children on ART. Therefore, continuous screening of anaemia and nutritional treatment is essential in these patients.

Survival analysis and predictors of mortality among adult HIV/AIDS patients initiated antiretroviral therapy from 2010 to 2015 in Dubti General Hospital, Afar, Ethiopia: A retrospective cohort study.

Background: Although antiretroviral therapy (ART) is well accepted to increase survival of patients with HIV/AIDS, AIDS related deaths continue to be a major problem in sub-Saharan Africa like Ethiopia. Studies have showed variable findings in the survival status of patients with HIV/AIDS initiating ART, and there was no such study in the study area. Therefore, purpose of this study was to determine the survival and predictors of mortality among HIV/AIDS patients starting taking ART in Dubti General Hospital, Afar, Ethiopia. Methods: A 5 year retrospective cohort study was performed among 702 HIV/AIDS patients aged ≥15 years that started ART between December 31, 2010, and December 31, 2015 in Dubti General Hospital, Afar, Ethiopia. A simple random sampling technique was used to select the study subjects from each WHO stage based stratum. Socio-demographic, clinical and survival status data were extracted by reviewing patients' records. Data were analyzed by using SPSS Version 21. Kaplan-Meier and Cox-regression models were used to estimate survival, and explore predictors of mortality. Variables with a p value of <0.05 in multivariate Cox regression analysis were considered statistically significant. Results: Among 702 study participants, 82 (11.7%) died during follow up, and the overall incidence rate of mortality was 5.81 per 100 person-years. Identified predictors of mortality were being not married (AHR = 3.71, 95% CI: 1.97-6.99), had no formal education (AHR = 2.33, 95% CI: 1.33-4.38), bedridden functional status (AHR = 5.91, 95% CI: 2.71-12.88), advanced WHO stage III and IV (AHR = 4.36, 95% CI: 2.20-8.64), BMI 16-18.4 kg/m2 (AHR = 3.03, 95% CI: 1.50-6.13), and BMI<16.0 kg/m2 (AHR = 5.47; 95% CI: 2.85-10.50), CD4 count ≤50 cells/mm3 (AHR = 6.62, 95% CI: 4.73-8.52), hemoglobin <8 g/dl (AHR = 5.21; 95% CI: 2.64-10.26), not used cotrimoxazole prophylaxis therapy (AHR = 2.78, 95% CI: 1.61-4.73), stavudine based regimen (AHR = 2.34, 95% CI: 1.32-4.13), and zidovudine based regimen (AHR = 2.49, 95% CI: 1.41-4.39). Conclusion: High mortality was observed in this cohort, and participants with stage III and IV, low CD4 count, low hemoglobin level, bed ridden functional status, low BMI should be closely monitored even with the scarce resources. In addition, the use of cotrimoxazole prophylaxis therapy should be more encouraged to increase survival.

A qualitative inquiry into the patient-related barriers to linkage and retention in HIV care within the community setting.

Background: People with the Human Immunodeficiency Virus (PWH) experience barriers to care within the community that impedes their progress from when they discover that they are HIV positive to becoming virally suppressed. For individuals with HIV to achieve sustained viral suppression, they must be linked to care to start receiving anti-retroviral therapy and remain retained in care for continuous treatment. However, HIV surveillance data shows that many PWH are not linked to care and become lost to continuous follow-up care. Although pharmacists, PWH, and social workers interact with one another and are aware of their roles in HIV care, their perspectives on barriers to linkage and retention in care have not been investigated collectively. Objectives: Explore the perspectives of PWH, pharmacists, and social workers on barriers to linkage and retention of HIV care within the community setting. Methods: Convenience sampling was used to recruit 15 stakeholders (five PWH, five community pharmacists, and five social workers) who participated in 1-h, semi-structured interviews based on three domains of the Patient-centered Medical Home Model including (1) experiences (individual and system-level barriers to care experienced by PWH), (2) activities (social workers and pharmacists initiatives that impact adherence to care)and (3) interventions (critical issues pharmacists can address in the community to engage PWH in their HIV care). We conducted a directed content analysis based on deductive coding. To establish rigor, we focused on Lincoln and Guba's criteria of rigorous qualitative methodology: credibility, dependability, confirmability, and transferability. Similarities and divergences of themes were discussed during data analysis and agreement was reached before interpretation. Results: Emergent themes uncovered barriers to linkage and retention in HIV care as HIV-related stigma, having mental health illnesses including a history of substance abuse and social determinants of health such as homelessness, food insecurity, and insurance issues. Conclusion: The perspectives of pharmacists, social workers, and PWH can provide insight into barriers that should be identified and addressed in people living with HIV to enhance their linkage and retention in care.

Treatment of ocular-involving monkeypox virus with topical trifluridine and oral tecovirimat in the 2022 monkeypox virus outbreak.

Purpose: To report a case of ocular involving monkeypox infection in the United States during the 2022 outbreak, and to review the literature regarding its clinical manifestations and management known to date. Observations: A 36-year-old man with well controlled HIV presented to the emergency department with anal pain, diffuse rash, right eye pain, and right eye redness after he tested positive for monkeypox one week prior. Ocular examination showed bilateral periorbital vesicular lesions, right eye conjunctival injection, and a single white plaque on his right medial bulbar conjunctiva. Macular, vesicular, and pustular lesions were noted throughout his body, including the genital and perianal region. His ocular and systemic symptoms completely resolved after treatment with a ten-day course of 1% trifluridine and moxifloxacin drops in both eyes, as well as two weeks of oral tecovirimat. Conclusion and Importance: In July of 2022, monkeypox virus was declared a global health emergency by the World Health Organization; however, there are no standard guidelines for monkeypox treatment. Data on its clinical presentation and course, especially pertaining to ocular manifestations, is limited. We highlight the importance of recognizing ophthalmic manifestations of monkeypox virus and a possible therapeutic approach to help guide the management of these patients.

Doravirine/tenofovir disoproxyl fumarate/lamivudine-induced alopecia: A case report.

We report here a case of alopecia probably caused by the fixed dose combination of doravirine/tenofovir disproxil fumarate/lamivudine (DOR/TDF/3TC) in a 46-year-old male living with HIV, previously treated with tenofovir disproxil fumarate and lamivudine-containing antiretroviral combinations. After having excluded other causes of hair loss such as sexually transmitted disease or drugs associated with alopecia, as well as poor immune-virologic conditions (i.e. low CD4+ cell count and/or high HIV viral load), a toxic effect of doravirine might be hypothesized. DOR/TDF/3TC was immediately stopped and rilpivirine plus tenofovir alafenamide fumarate/emtricitabine was started. Four weeks after changing the antiretroviral regimen, the patient reported signs of hypopigmented hair regrowth. The association between the episode of alopecia and DOR/TDF/3TC was scored as probable according to the Naranjo causality scale. We concluded that alopecia was probably related to DOR but whether it is self-limiting, cannot be predicted at this stage.

The prevalence and incidence of HIV in the ART era (2006-2016) in North West Tanzania.

BACKGROUND: Sub-Saharan countries bear a disproportionate percentage of HIV infections and HIV-related deaths despite the efforts to strengthen HIV prevention and treatments services, including ART. It is important to demonstrate how these services have contributed to reducing the epidemic using available population data. METHODS: We estimated the prevalence and incidence rates from a cohort running over 23 years in Magu District, Mwanza Region-North West Tanzania. Adults 15 years and over who were residents of the Kisesa observational HIV cohort study between 2006 and 2016 were eligible for inclusion. Survival analysis was used to calculate person-time at risk, incidence rates and 95% confidence intervals (CIs). Cox regression models were used for the risk factor analyses disaggregated by sex and age group. RESULTS: The HIV prevalence in the sero-surveys decreased from 7.2% in 2006/07 to 6.6% in 2016, with a notable decrease of over 50% for both men and women aged 15-24 years. The incidence rate for HIV was estimated to be 5.5 (95% CI 4.6-6.6) per 1,000 person-years in women compared to 4.6 (95% CI 3.5-5.8) in men, with a decrease over time. Despite the availability of ART services, the uptake is still small. CONCLUSIONS: New infections are still occurring, with high HIV incidence in individuals aged below 45 years. With new guidelines and the 95-95-95 UNAIDS target, prevalence and incidence must be adequately assessed. In addition, there is a need for additional efforts to assess the impact of HIV/AIDS prevention programmes and intervention services, especially in these areas where resources are limited.

A case of central nervous system infection by Candida famata in an immunosuppressed patient with HIV-1 infection.

Invasive fungal infections caused by Candida species are increasingly observed in immunosuppressed patients. Candida albicans is the more often identified species and neurocandidiasis is associated with high mortality rates. Diagnosis and treatment of these infections are frequently challenging. We report a case of central nervous system infection caused by Candida famata in an HIV-1 infected patient. To our best knowledge this is just the second published case of neural infection by this agent.

Factors influencing adherence to antiretroviral therapy among HIV/AIDS patients in the Ga West Municipality, Ghana.

Objectives: Antiretroviral therapy (ART) is used to suppress the HIV viral load but requires optimal adherence to be effective. This study examined the factors influencing ART adherence among HIV-positive clients in the Ga West Municipality, Ghana using the Health Belief Model (HBM). Methods: A facility-based cross-sectional design was adopted among 397 HIV clients aged 18 years and above. Data were collected using an interviewer-administered questionnaire and analysed using Stata version 16.0. Binary logistic regression was performed at the P < 0.05 level. Results: Adherence to ART was 44.6%. Clients who took less than 30 minutes to reach ART sites were 59% less likely to adhere to ART (odds ratio (OR) 0.41, 95% confidence interval (CI) 0.20-0.82). Clients who thought they lost income when they went to obtain their ART refill were more likely to adhere to ART (OR 1.71, 95% CI 1.04-2.83), as were those who developed side effects (OR 1.74, 95% CI 1.05-2.89) (perceived barriers). Clients who had confidence in their ability to take their medications (self-efficacy) (OR 1.86, 95% CI 1.05-3.31) and those who received reminders from health workers (cues to action) (OR 1.91, 95% CI 1.04-3.53) were more likely to adhere to ART. Conclusions: Interventions should focus on increasing client confidence in adhering to ART. Providers should be empowered to provide reminders to patients.

Combination strategies to durably suppress HIV-1: Soluble T cell receptors.

Immunotherapeutic interventions to enhance natural HIV-specific CD8+ T cell responses, such as vaccination or adoptive T cell transfer, have been a major focus of HIV cure efforts. However, these approaches have not been effective in overcoming viral immune evasion mechanisms. Soluble T cell receptor (TCR) bispecifics are a new class of 'off-the-shelf' therapeutic designed to address these limitations. These biologics are built on the Immune mobilising monoclonal TCRs against X disease (ImmTAX) platform, which was pioneered in oncology and recently validated by the FDA's approval of tebentafusp for treatment of metastatic uveal melanoma. ImmTAV® are an application of this technology undergoing clinical development for the elimination of chronic viral infections. ImmTAV molecules comprise an affinity-enhanced virus-specific TCR fused to an anti-CD3 effector domain. Engineering of the TCR confers extraordinary specificity and affinity for cognate viral antigen and the anti-CD3 enables retargeting of non-exhausted cytolytic T cells, irrespective of their specificity. These features enable ImmTAV molecules to detect and kill infected cells, even when expressing very low levels of antigen, bypassing ineffective host immune responses. Furthermore, the modularity of the platform allows for engineering of TCRs that effectively target viral variants. In this review, we discuss the progress made in the development of ImmTAV molecules as therapeutics for functional cure of chronic hepatitis B and HIV, from concept to the clinic.

Antiplatelet Effects of Clopidogrel Vs Aspirin in Virologically Controlled HIV: A Randomized Controlled Trial.

Patients with HIV exhibit platelet activation and increased risk of cardiovascular disease, the prevention of which is not fully known. Fifty-five HIV-positive patients were randomized to clopidogrel, aspirin, or no-treatment for 14 days, and the platelet phenotype and ability to induce endothelial inflammation assessed. Clopidogrel as opposed to aspirin and no-treatment reduced platelet activation (P-selectin and PAC-1 expression). Compared with baseline, platelet-induced proinflammatory transcript expression of cultured endothelial cells were reduced in those assigned to clopidogrel, with no change in the aspirin and no-treatment arms. In HIV, clinical trials of clopidogrel to prevent cardiovascular disease are warranted. (Antiplatelet Therapy in HIV; NCT02559414).

Intimate partner violence and HIV treatment adherence in urban South Africa: Mediating role of perinatal common mental disorders.

Background: Antiretroviral therapy (ART) has potential to eliminate perinatal HIV infections, but adherence to ART in late pregnancy and postpartum is often suboptimal. Intimate partner violence (IPV) may influence non-adherence among perinatal women living with HIV (WWH), but few quantitative studies have examined this over time or explored mechanisms for this association. Methods: We used secondary data from a parent trial in Johannesburg comprising WWH from the control arm (n=63) and WWH ineligible for the trial (n=133). Trained nurse researchers administered questionnaires at first antenatal visit on past-year psychological, physical, and/or sexual IPV (WHO instrument), socio-demographics (age, food security, education), and perinatal common mental symptoms of depression (Hospital Anxiety and Depression Screener-d); anxiety (HADS-a); post-traumatic stress disorder (PTSD; Harvard Trauma Questionnaire). At endline visit 2-4 months postpartum, nurse researchers assessed self-reported ART adherence using a visual analog scale (with ≥95% considered "good"). We fitted structural equation models (SEM) in MPlus to explore direct and indirect effects of IPV on ART adherence. Results: Of 196 perinatal WWH, 53.1% reported IPV exposure at baseline. The majority of participants (85.7%) had good perinatal ART adherence. In adjusted models, IPV at baseline was associated with halved odds of good adherence (aOR=0.51, 95%CI=0.20-0.96). IPV was associated with higher adjusted odds of probable depression (aOR=4.64), anxiety (aOR=2.85), and PTSD (aOR=3.42). In SEM, IPV had a direct (standardized coef=-0.22) and indirect effect (coef=-0.05) on ART via common mental disorders. The total effect of IPV on perinatal adherence was of moderate size (coef= -0.27) and the model had good fit (CFI=0.972; TLI=0.969; RMSEA=0.045; SRMR=0.076). Conclusion: IPV was longitudinally associated with perinatal ART non-adherence in part due to its relationship with mental health symptomology. Addressing IPV within clinical care has potential to improve perinatal mental health, maternal HIV outcomes, and HIV-free infant survival.

Cost-effectiveness of oral pre-exposure prophylaxis and expanded antiretroviral therapy for preventing HIV infections in the presence of drug resistance among men who have sex with men in China: A mathematical modelling study.

Background: Oral pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) can effectively prevent HIV infections among men who have sex with men (MSM), but the emergence and transmission of HIV drug-resistance (HIVDR) may compromise their benefits. The costs and benefits of expanding PrEP and ART coverage in the presence of HIVDR in China remain unknown. Methods: We developed a comprehensive dynamic transmission model incorporating the transmitted (TDR) and acquired (ADR) HIV drug resistance. The model was calibrated by the HIV surveillance data from 2009 to 2019 among MSM in Jiangsu Province, China, and validated by the dynamic prevalence of ADR and TDR. We aimed to investigate the impact of eight intervention scenarios (no PrEP, 20%, 50% or 80% of PrEP, without (77% coverage) or with (90% coverage) expanded ART) on the HIV epidemic trend and cost-effectiveness of PrEP over the next 30 years. Findings: 20% or 50% PrEP + 90% ART would be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 25,417 (95% confidence interval [CI]: 12,390-38,445) or 47,243 (23,756-70,729), and would yield 154,949 (89,662-220,237) or 179,456 (102,570-256,342) incremental quality-adjusted life-years (QALYs) over the next 30 years. No PrEP + 90% ART would yield 125,211 (73,448-176,974) incremental QALYs and be cost-saving. However, 20-80% PrEP + 77% ART and 80% PrEP + 90% ART with ICER of $77,862-$98,338 and $63,332, respectively, and were not cost-effective. A reduction of 64% in the annual cost of oral PrEP would make it highly cost-effective for 50% PrEP + 90% ART. Interpretation: 20% or 50% PrEP + 90% ART is cost-effective for HIV control in the presence of HIVDR. Expanded ART alone may be the optimal policy under the current limited budgets. Funding: National Natural Science Foundation of China, the National S&T Major Project Foundation of China.