Effect of intake of probiotics and probiotic fermented foods on clinical outcomes among people living with HIV: A systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to determine the effect of probiotics and of probiotic-fermented foods on CD4 T-cell count, viral load, anaemia and body mass index (BMI) among people living with HIV (PLHIV). METHODS: In this article, we systematically reviewed the evidence on the influence of probiotic supplementation on CD4 lymphocyte count, viral load and anaemia among PLHIV on highly active antiretroviral therapy (HAART) and those who were HAART-naive. Medical literature databases identified randomised trials and pre-post studies of probiotic supplementation and HIV-related outcomes, and random effects meta-analysis was conducted. RESULTS: The preponderance of the evidence suggests that probiotic supplementation only improved CD4 lymphocyte count modestly, with quantitatively greater impact among individuals who were HAART-naive compared to HAART-experienced individuals. Probiotic supplementation improved CD4 lymphocyte count by 53 cells/mm3 (95% CI: 22 to 85) from 18 studies. Probiotic supplementation however reduced haemoglobin concentration by -2.1 g/L (95% CI: -4.0 to -0.2). Although viral load remain unchanged in HAART-experienced participants following probiotic supplementation, HAART-naïve participants saw a decrease in viral load. There were too few studies on the impact of probiotic supplementation on viral load (N = 1). CONCLUSION: Probiotic supplementation resulted in a modest increase in CD4 lymphocyte count among HAART-naive individuals with no significant change observed among HAART-experienced ones. Viral load and haemoglobin concentration also remained unchanged following probiotic supplementation. Further rigorous and well-powered studies may evaluate the effect of probiotic supplementation on important clinical outcomes among PLHIV on HAART.

Evaluating experiences of HIV-related stigma among people living with HIV diagnosed in different treatment eras in British Columbia, Canada.

There is mixed evidence on whether experiences of HIV-related stigma are mitigated with lived experience. We sought to examine whether people living with HIV (PLWH) with longer living experience reported varying levels of HIV-related stigma. Between January 2016-September 2018, we used purposive sampling to enrol PLWH aged ≥19 across British Columbia, Canada, where participants completed the 10-item Berger HIV Stigma Scale. We conducted bivariate analyzes examining key sociodemographic characteristics and HIV-related stigma scores. Multivariable linear regression modelled the association between year of HIV diagnosis by treatment era and HIV-related stigma scores. We enrolled 644 participants; median age at enrolment was 50 years (Q1-Q3: 42-56), with 37.4% (n = 241) diagnosed before the year 2000. The median HIV-stigma scores of all participants (19.0, Q1-Q3: 13-25, range 0-40) stratified by treatment era were: 17.0 (pre-1996), 20.0 (1996-1999), 20.0 (2000-2009), 19.0 (2010-2018) (p = 0.03). While there was a significant association at the univariate level, year of HIV diagnosis by treatment era was not associated with stigma scores after controlling for age, gender, HIV key populations, ethnicity, relationship status, social support, and ever having a mental health disorder diagnosis. This suggests that PLWH still experience HIV-related stigma today, compared to those diagnosed in earlier time periods.

Impact of serious adverse drug reactions on the quality of life of patients on highly active antiretroviral therapy in Maiduguri, northeast Nigeria: a four-year retrospective study.

ABSTRACTSerious adverse drug reactions (sADRs) have a serious impact on the progress being made in providing antiretroviral therapy. The presence of HIV/AIDS and its complications associated with sADRs, has a negative effect on the quality of life (QoL) of people living with HIV/AIDS (PLWHA). This was a descriptive retrospective cohort study of 400 adult HIV patients in which the QoL of PLWHA with sADRs was compared to patients that did not experience ADR who had been on antiretroviral therapy (ART) was followed up for 48 months using the WHOQOL-HIV BREF to measure QoL. Out of 400 patients, 373 (93.25%) respondents completed the study with an overall mean age was 40.8 years (SD ± 8.64). One hundred and ninety-nine patients (53.4%) reported to have experiencing sADR. The response consistently showed significantly higher mean scores in the QoL of patients who had no ADRs in the psychological, social and environments state of health domains compared to those who had ADRs with mean scores (P = 0.000, 0.037 and 0.028), respectively. This study revealed significantly higher scores in patients who had no ADRs compared to those who had ADRs. Low QoL due to serious ADR may add additional burden to HIV disease and complications, and the related discrimination often faced by PLWHA. This study would help clinicians pay serious attention to identifying and promptly managing ADR.

Weight loss and mortality in people living with HIV: a systematic review and meta-analysis.

BACKGROUND: In the first reported cases of human immunodeficiency virus (HIV) infection, people living with HIV (PLHIV) suffered weight loss, which was an independent predictor of mortality. Highly active antiretroviral therapy (HAART) has changed this scenario for ideal weight, overweight, and even obesity. However, some PLHIV, even on HAART, continue to lose weight. Thus, the guiding question of the study was: do PLHIV hospitalized using HAART with weight loss have higher mortality than hospitalized PLHIV using HAART without weight loss? METHOD: A systematic review and meta-analysis of prospective cohort studies published in English, Spanish, or Portuguese, searched in the MedLine, Embase, and LILACS databases from March 2020, until October 2023, reported by MOOSE. We analyzed the methodological quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Tool for Cohort Studies; used the risk ratio (RR) to calculate the probability of hospitalized PLWH who lost weight dying, applied the random effect model and created the funnel plot. We used the inverse variance test estimated by the Mantel-Haenszel method, considering a 95% confidence interval (CI), heterogeneity (I2), total effect size (Z), and significance value of p < 0.05. We performed a sensitivity analysis with meta-regression and meta-analyses on subgroups to diagnose influence and outliers. The quality of evidence and strength of recommendation were analyzed using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE). RESULTS: We included 10 of the 711 studies identified, totaling 1,637 PLHIV. The studies were from South Africa (1), Canada (1), China (1), Brazil (1), Cameroon (1), Ethiopia (1), Thailand (1), Colombia (1), and Tanzania (2), from 1996 to 2017. The average age of the participants was 33.1 years old, and the male was predominant. The leading causes of hospital admission were related to co-infections, and the average hospitalization time was 20.5 days. The prevalence of death in hospitalized PLHIV using HAART who lost weight was 57.5%, with a 1.5 higher risk of dying (RR: 1.50, 95% CI: 1.03, 2.19, p = 0.04) than hospitalized PLHIV who did not lose weight. CONCLUSION: We concluded, with a very low confidence level, that that weight loss significantly increased the risk of death in hospitalized PLWH using HAART. TRIAL REGISTRATION AND FUNDING: PROSPERO International Prospective Register of Systematic Reviews CRD42020191246 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191246 .

High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis.

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10­1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76­1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.

Highly active antiretroviral therapy discontinuation time is associated with therapeutic failure among human immunodeficiency virus (HIV)-infected immigrant adults: A cohort study from a Peruvian referral hospital during the Venezuelan exodus.

OBJECTIVE: To evaluate the association between Highly Active Antiretroviral Therapy (HAART) discontinuation time and therapeutic failure (TF) in Venezuelan immigrants with HIV that restart HAART. METHODS: We carried out a retrospective cohort study in a large hospital in Peru. We included Venezuelan immigrants who restarted HAART and were followed over at least 6 months. The primary outcome was TF. Secondary outcomes were immunologic (IF), virologic (VF) and clinical (CF) failures. The exposure variable was HAART discontinuation, categorised as no discontinuation, less than 6 months, and 6 months or more. We applied generalised linear models Poisson family with robust standard errors to calculate crude (cRR) and adjusted (aRR) relative risks by statistical and epidemiological criteria. RESULTS: We included 294 patients, 97.2% were males, and the median age was 32 years. Out of all the patients, 32.7% discontinued HAART for less than 6 months, 15.0% discontinued for more than 6 months and the remaining 52.3% did not discontinue. The cumulative incidence of TF was 27.9%, 24.5% in VF, 6.0% in IF and 6.0% in CF. Compared with non-discontinued HAART patients, the discontinuation for less than 6 months (aRR = 1.98 [95% CI: 1.27-3.09]) and from 6 months to more (aRR = 3.17 [95% CI: 2.02-4.95]) increased the risk of TF. Likewise, treatment discontinuation of up to 6 months (aRR = 2.32 [95% CI: 1.40-3.84]) and from 6 months to more (aRR = 3.93 [95% CI: 2.39-6.45]) increased the risk of VF. CONCLUSIONS: HAART discontinuation increases the probability of TF and VF in Venezuelan immigrants.

Zinc improves sexual and erectile function in HAART-treated rats via the upregulation of erectogenic enzymes and maintenance of redox balance.

PURPOSE: HAART has been shown to impair sexual function and penile erection via perturbation of penile redox balance, while zinc has been established to exert antioxidant activity. Therefore, this study focused on the role and associated molecular mechanism of zinc in HAART-induced sexual and erectile dysfunction. MATERIALS AND METHODS: Twenty male Wistar rats were randomly grouped into four (n = 5 rats per group); the control, zinc-treated, HAART-treated, and HAART + zinc-treated groups. Treatments were per os daily for eight weeks. RESULTS: Zinc co-administration significantly improved HAART-induced increase in the latencies of mount, intromission, and ejaculations. Zinc also attenuated HAART-induced reduction in the motivation to mate, penile reflex/erection, and frequencies of mount, intromission, and ejaculations. In addition, zinc co-treatment improved HAART-induced decline in penile NO and cGMP, dopamine, and serum testosterone. More so, zinc prevented HAART-induced rise in penile activities of monoamine oxidase, acetylcholinesterase, phosphodiesterase-5, and arginase. Furthermore, concomitant treatment with zinc ameliorated HAART-induced penile oxidative stress and inflammation. CONCLUSION: In conclusion, our present findings show that zinc improves sexual and erectile function in HAART-treated rats by upregulating erectogenic enzymes via the maintenance of penile redox balance.

Excess mortality and associated factors among people living with HIV initiating highly active antiretroviral therapy in Luzhou, China 2006-2020.

BACKGROUND: To estimate crude mortality, excess mortality, and standardized mortality rates (SMR) among people living with HIV (PLHIV) initiating highly active antiretroviral therapy (HAART) in Luzhou, China 2006-2020, and assess associated factors. METHODS: PLHIV initiating HAART in the HIV/AIDS Comprehensive Response Information Management System (CRIMS) in Luzhou, China 2006-2020 were included in the retrospective cohort study. The crude mortality, excess mortality, and SMR were estimated. Multivariable Poisson regression model was used for analyzing risk factors associated with excess mortality rates. RESULTS: The median age among 11,468 PLHIV initiating HAART was 54.5 years (IQR:43.1-65.2). The excess mortality rate decreased from 1.8 deaths/100 person-years (95% confidence interval [CI]:1.4-2.4) in 2006-2011 to 0.8 deaths/100 person-years (95%CI:0.7-0.9) in 2016-2020. SMR decreased from 5.4 deaths/100 person-years (95%CI:4.3-6.8) to 1.7 deaths/100 person-years (95%CI:1.5-1.8). Males had greater excess mortality with the eHR of 1.6 (95%CI:1.2-2.1) than females. PLHIV with CD4 counts ≥ 500 cells/µL had the eHR of 0.3 (95%CI:0.2-0.5) in comparison to those with CD4 counts < 200 cells/µL. PLHIV with WHO clinical stages III/IV had greater excess mortality with the eHR of 1.4 (95%CI:1.1-1.8). PLHIV with time from diagnosis to HAART initiation ≤ 3 months had the eHR of 0.7 (95%CI:0.5-0.9) compared to those with time ≥ 12 months. PLHIV with initial HAART regimens unchanged and viral suppression had the eHR of 1.9 (95%CI:1.4-2.6) and 0.1 (95%CI:0.0-0.1), respectively. CONCLUSIONS: The excess mortality and SMR among PLHIV initiating HAART in Luzhou, China decreased substantially from 2006 to 2020, but the mortality rate among PLHIV was still higher than general population. PLHIV who were male, with baseline CD4 counts less than 200 cells/µL, WHO clinical stages III/IV, time from diagnosis to HAART initiation ≥ 12 months, initial HAART regimens unchanged, and virological failure had a greater risk of excess deaths. Early and efficient HAART would be significant in reducing excess mortality among PLHIV.

In HIV-Infected Immunological Non-Responders, Hepatitis C Virus Eradication Contributes to Incomplete Normalization of Systemic Inflammation Indexes, but Does Not Lead to Rapid CD4+ T-Cell Count Recovery.

In HIV-positive individuals taking antiretroviral therapy, coinfection with hepatitis C virus (HCV) increases systemic inflammation, which interferes with the CD4+ T-cells regeneration. This study evaluated the effect of HCV eradication on systemic inflammation and CD4+ T-cell regeneration in patients who gave poor response to antiretroviral therapy, the so-called "immunological non-responders" (INRs). HIV-infected patients who received a course of direct-acting antivirals for treating hepatitis C were examined. The control groups included HIV/HCV-coinfected INRs and relatively healthy volunteers. It was established for the first time that HCV eradication is not accompanied by a complete suppression of systemic inflammation, but improves the T-cell pool composition: in INRs, the blood CD4+/CD8+ T-lymphocyte ratio increases and approaches those of healthy individuals. Apparently, in INRs treated for hepatitis C, the immune system recovery takes time and may be incomplete.

Predictors of knowledge of and access to biomedical prevention among MSM and transgender men in Latin America: Results from the Latin American internet survey.

INTRODUCTION: HIV is still a central public health issue in Latin America, disproportionally affecting key populations. Knowledge and access to biomedical prevention strategies, including treatment as prevention (TASP) or undetectable = untransmissible (U=U), pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), are the first steps to increasing uptake. We used data from the Latin American MSM Internet Survey (LAMIS) to describe knowledge and access to biomedical HIV prevention strategies among gay, bisexual, transgender and other men who have sex with men (MSM) living in 18 Latin American countries. METHODS: We compared LAMIS data across countries and according to age categories using frequencies and percentages. We also used multivariable models to explore whether age, gender identity, sexual identity, steady partnership, HIV status and education were independently associated with outcomes. RESULTS: In all, 55 924 participants were included. Most were cisgender (99%) and identified as gay/homosexual (77%) or bisexual (17%). Schooling levels were very high, with 89% reporting highest attained education as tertiary level, university or post-graduation. In total, 16% had been previously diagnosed with HIV; of those, rates of undetectable viral load varied from 60% in Venezuela to 83% in Brazil. Overall, 54%, 54% and 52% of participants already knew about PEP, PrEP and U=U, respectively. Participants from Brazil and those aged between 26 and 55 years, living with diagnosed HIV and having a gay/homosexual identity had greater levels of awareness about biomedical prevention strategies. CONCLUSIONS: Our study highlights gaps in HIV prevention campaigns directed to MSM in Latin America resulting in low uptake of biomedical prevention methods.

The impact of Option B+ on mother-to-child transmission of HIV in Africa: A systematic review.

OBJECTIVE: In 2015, the WHO released new guidelines to reduce mother-to-child transmission (MTCT) of HIV. The recommendations, known as Option B+, included initiation of lifelong highly active antiretroviral therapy regardless of CD4 count for all HIV-positive pregnant and breastfeeding mothers. For infants, exclusive breastfeeding for 6 months and antiviral therapy were sanctioned. Targets of <5% transmission in breastfeeding populations and <2% in non-breastfeeding populations were set. This review evaluated the impact of Option B+ on MTCT in African countries. METHODS: Using the PRISMA guidelines, a systematic search of PubMed and Google Scholar databases was conducted to identify relevant studies published between 2015 and 2021. All studies meeting inclusion criteria were evaluated. RESULTS: Of the 687 references screened, 22 studies from 11 countries (Cameroon, Ethiopia, Lesotho, Malawi, Rwanda, South Africa, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe) met inclusion criteria. Six studies reported MTCT rates of <2%, 16 studies reported rates of 2-5% and two studies (Uganda and Zambia) reported 6% or more. Rates varied within the same study at different time points postpartum and amongst studies from the same country. Overall, reported MTCT rates appear to be close to WHO targets. However, diverse study designs, selection bias, extensive loss to follow-up and undocumented adherence rates to Option B+ protocols may significantly underestimate MTCT rates of HIV in Africa. CONCLUSIONS: Standardised protocols for impact evaluation must be established to provide evidenced-based data on the efficacy of Option B+ in Africa.

Association between frailty phenotype, quantification of plasma HIV-1 RNA, CD4 cell count and HAART in HIV-positive subjects: a systematic review and meta-analysis of observational studies.

HIV infection causes a constant activation of the immune system and contributes to an enhanced systemic pro-inflammatory cytokine milieu, which has been associated with premature aging and frailty. We performed a systematic review and meta-analysis to analyze whether the HIV-1 RNA load, CD4+ T-lymphocyte counts and exposure to HAART in HIV-positive subjects are associated with frailty phenotype. Searches were performed in PubMed, SCOPUS, Lilacs, Web of Science, Google Scholar, and OpenThesis databases. We used the odds ratio as a measure of the association. We used either a fixed or random-effects model to pool the results of individual studies depending on the presence of heterogeneity. Eleven studies were included in the review. Data from 8035 HIV-positive subjects were analyzed; 2413 of the subjects had viral load detectable, 981 had a CD4T-cell count <350 cells/µL, and 1342 had HAART exposure information. We found an association between frailty and CD4T-cell count <350 cells/µL (OR 2.68, CI 95% 1.68-4.26, I2 = 46%), HIV-1 RNA load detectable (OR 1.71, CI 95% 1.38-2.12, I2 = 0%), and protease inhibitor-containing HAART regimen (OR 2.21, CI 95% 1.26-3.89, I2 = 0%). Further studies are necessary to evaluate the effects of other factors on the development of clinical features related to frailty.

Persons living with HIV treated in acute HIV infection report good health-related quality of life in Thailand.

The health-related quality of life (HRQoL) among persons living with HIV (PLWHA) who initiate ART during acute HIV infection (AHI) is not well studied. Participants in the SEARCH010/RV254 cohort initiated ART during AHI. They completed the Thai version of the World Health Organisation Quality of Life instrument-BREF (WHOQOL-BREF) and Patient Health Questionnaire-9 (PHQ-9) prior to ART initiation and 24 weeks later. Of 452 participants, 406 (90%) completed the WHOQOL-BREF. The median age was 26 years (IQR 22-31), and 98% were men. All WHOQOL-BREF domains demonstrated good internal consistency (Cronbach's alpha >0.70). Confirmatory factor analysis validated the WHOQOL-BREF model. 90% of Pearson correlations between domain scores and general facet items were >0.50. HRQoL in all domains was worse among those with at least moderately severe depression (PHQ-9 ≥ 10) (p<0.0001), supporting discriminant validity. At 24 weeks, there was an improvement of scores in all domains (physical, psychological, social, and environmental) and general facet items (p<0.0001), and the range of mean domain scores was 14.7-15.6 (SD 2.3-2.8). The majority of participants (58-63%) had improved HRQoL in the physical, psychological and environmental domains. It is concluded that HRQoL improves 6 months after initiation of ART in AHI, suggesting a benefit of early ART initiation.

Modelling trends of CD4 counts for patients on antiretroviral therapy (ART): a comprehensive health care clinic in Nairobi, Kenya.

BACKGROUND: In resource-limited settings, changes in CD4 counts constitute an important component in patient monitoring and evaluation of treatment response as these patients do not have access to routine viral load testing. In this study, we quantified trends on CD4 counts in patients on highly active antiretroviral therapy (HAART) in a comprehensive health care clinic in Kenya between 2011 and 2017. We evaluated the rate of change in CD4 cell count in response to antiretroviral treatment. We further assessed factors that influenced time to treatment change focusing on baseline characteristics of the patients and different initial drug regimens used. This was a retrospective study involving 432 naïve HIV patients that had at least two CD4 count measurements for the period. The relationship between CD4 cell count and time was modeled using a semi parametric mixed effects model while the Cox proportional hazards model was used to assess factors associated with the first regimen change. RESULTS: Majority of the patients were females and the average CD4 count at start of treatment was 362.1 [Formula: see text]. The CD4 count measurements increased nonlinearly over time and these trends were similar regardless of the treatment regimen administered to the patients. The change of logarithm CD4 cell count rises fast for in the first 450 days of antiretroviral initiation. The average time to first regimen change was 2142 days. Tenoforvir (TDF) based regimens had a lower drug substitution(aHR 0.2682, 95% CI:0.08263- 0.8706) compared to Zidovudine(AZT). CONCLUSION: The backbone used was found to be associated with regimen changes among the patients with fewer switches being observed, with the use of TDF when compared to AZT. There was however no significant difference between TDF and AZT in terms of the rate of change in logarithm CD4 count over time.

Predictors of mortality among people living with HIV in the test and treat era within rural Uganda: a retrospective cohort study.

Background: Uganda adopted the test and treat strategy in 2016 where all people living with HIV are initiated on antiretroviral drugs irrespective of CD4 count and WHO clinical stage, as one of the major strategies to end the HIV epidemic by 2030. Despite these measures, there are still more than 2 000 HIV-related death annually. The study aim was to determine the mortality rate and factors predictive of mortality in the test and treat era among people living with HIV in rural Uganda.Methods: We conducted a retrospective cohort study among people living with HIV enrolled into care between January 2016 and December 2020 at Kabwohe Clinical Research Centre in south-western Uganda. Kaplan-Meier curves were used for survival analysis and Cox regression analysis at bivariate and multivariable levels was used to determine the adjusted hazard ratios (AHR) and identify predictors of death during the study period.Results: Of the 976 participants included in the study, 57.1% (557) were females while 42.9% (419) were males. The median age of the participants was 35 years. The average follow-up period was 2.9 years with an overall mortality rate of 0.99 per 100 person-years at risk. In multivariate analysis, the independent predictors for mortality were: CD4 < 200cells/mm³ (AHR 3.68; 95% CI 1.7-8.1), viral load ≥ 1 000 copies/ml (AHR 5.22; 95% CI 2.4-11.4) and a non-optimised antiretroviral regimen (AHR 4.08; 95% CI 1.5-0.8).Conclusion: There was a low mortality rate observed in this study with a higher risk of death associated with advanced HIV disease and unsuppressed initial viral load. The findings of the study therefore support efforts in early antiretroviral therapy initiation as it increases the likelihood of people living with HIV surviving and can accelerate efforts in ending the HIV epidemic by 2030.

Editing out HIV: application of gene editing technology to achieve functional cure.

Highly active antiretroviral therapy (HAART) successfully suppresses human immunodeficiency virus (HIV) replication and improves the quality of life of patients living with HIV. However, current HAART does not eradicate HIV infection because an HIV reservoir is established in latently infected cells and is not recognized by the immune system. The successful curative treatment of the Berlin and London patients following bone marrow transplantation inspired researchers to identify an approach for the functional cure of HIV. As a promising technology, gene editing-based strategies have attracted considerable attention and sparked much debate. Herein, we discuss the development of different gene editing strategies in the functional cure of HIV and highlight the potential for clinical applications prospects.

HIV, Vascular Risk Factors, and Cognition in the Combination Antiretroviral Therapy Era: A Systematic Review and Meta-Analysis.

OBJECTIVES: Mounting evidence indicates that vascular risk factors (VRFs) are elevated in HIV and play a significant role in the development and persistence of HIV-associated neurocognitive disorder. Given the increased longevity of people living with HIV (PLWH), there is a great need to better elucidate vascular contributions to neurocognitive impairment in HIV. This systematic review and meta-analysis examine relationships between traditional VRFs, cardiovascular disease (CVD), and cognition in PLWH in the combination antiretroviral therapy era. METHODS: For the systematic review, 44 studies met inclusion criteria and included data from 14,376 PLWH and 6,043 HIV-seronegative controls. To better quantify the contribution of VRFs to cognitive impairment in HIV, a robust variance estimation meta-analysis (N = 11 studies) was performed and included data from 2139 PLWH. RESULTS: In the systematic review, cross-sectional and longitudinal studies supported relationships between VRFs, cognitive dysfunction, and decline, particularly in the domains of attention/processing speed, executive functioning, and fine motor skills. The meta-analysis demonstrated VRFs were associated with increased odds of global neurocognitive impairment (odds ratio [OR ]= 2.059, p = .010), which remained significant after adjustment for clinical HIV variables (p = .017). Analyses of individual VRFs demonstrated type 2 diabetes (p = .004), hyperlipidemia (p = .043), current smoking (p = .037), and previous CVD (p = .0005) were significantly associated with global neurocognitive impairment. CONCLUSIONS: VRFs and CVD are associated with worse cognitive performance and decline, and neurocognitive impairment in PLWH. Future studies are needed to examine these relationships in older adults with HIV, and investigate how race/ethnicity, gender, medical comorbidities, and psychosocial factors contribute to VRF-associated cognitive dysfunction in HIV.

Sociodemographic and psychosocial predictors of longitudinal antiretroviral therapy (ART) adherence among first-time ART initiators in Cape Town, South Africa.

First-time antiretroviral therapy (ART) initiators may be more vulnerable to poor ART adherence because they may be coping with a new HIV diagnosis, facing logistical challenges to accessing and adhering to ART for the first time, and have not yet developed support networks or the skills to support long-term adherence. We recruited 324 participants in two HIV clinics near Cape Town, South Africa. Sociodemographic/psychosocial factors were measured at baseline and self-reported adherence at the 6 month follow-up. We conducted multivariable regression to determine which baseline factors were associated with 6-month adherence. A better patient-clinic relationship score (OR: 1.08 [95% CI: 1.05-1.11]) was associated with higher adherence. A drug use problem (0.51 [0.29-0.87]), higher social isolation (0.93 [0.87-0.99]), and greater number of years living with HIV before initiating ART (0.92 [0.86-1.00]) were associated with adherence levels below 90%. Patient-clinic relationships and social support are key psycho-social factors in early adherence behavior. Reducing drug use problems through targeted screening and early intervention may improve ART adherence.

Changes in body mass index among people living with HIV who are new on highly active antiretroviral therapy: a systematic review and meta-analysis.

In the era of highly active antiretroviral therapy (HAART), obesity is increasingly being reported among people living with HIV (PLHIV). In this study, we reviewed published literature on body mass index (BMI) changes among treatment-naïve adult PLHIV who started HAART and remained on treatment for at least six months. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, four databases were searched, and results of included studies were synthesized to describe the BMI trend among PLHIV on treatment. The search generated 4948 studies, of which 30 were included in the qualitative synthesis and 18 were eligible for the meta-analysis. All the studies showed an increase in group BMI. HAART was associated with increase in BMI (pooled effect size [ES] = 1.58 kg/m2; 95% CI: 1.36, 1.81). The heterogeneity among the 18 studies was high (I2 = 85%; p < .01). Subgroup analyses showed pooled ES of 1.54 kg/m2 (95% CI: 1.21, 1.87) and 1.63 kg/m2 (95% CI: 1.34, 1.91) for studies with follow-up ≤1 year and >1 year, respectively. We conclude that the greatest gain in BMI is in the initial 6-12 months on treatment, with minor gains in the second and subsequent years of treatment.

Histomorphological study of the effects of aqueous extract of Curcuma longa on highly active antiretroviral therapy-induced testicular toxicity.

This study evaluates the effects of highly active antiretroviral therapy (HAART) and Curcuma longa on testicular histology, stereological parameters, body weight and relative organ weights, seminal fluid, testosterone, follicle-stimulating hormone, the antioxidant marker malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) in adult male Wistar rat. Thirty-six adult male Wistar rats were grouped into A: distilled water (control); B: 100 mg/kg C. longa; C: 200 mg/kg C. longa; D: HAART only; E: HAART + 100 mg/kg C. longa; and F: HAART + 200 mg/kg C. longa. The rats were sacrificed after 8 weeks. Results showed a significant increase in abnormal morphology in group D when compared with group A. In group D, progressive sperm motility was significantly decreased compared with group F. The GSH level was significantly increased in group D compared with control group A, group E and group F. Histomorphological studies showed that HAART caused loss of germ cells and widening tubule lumen which were improved and partially restored by C. longa. This study suggests that C. longa improves testicular morphology and ameliorates HAART-induced toxicity. Further studies confirming putative mechanisms are required.