The aim of this research was to implement and evaluate guidelines that will be used by treatment support counsellors in an attempt to increase client adherence to antiretroviral treatment.

The aim of this research was to implement and evaluate guidelines that will be used by treatment support counsellors in an attempt to increase client adherence to antiretroviral treatment.

Thesis (DTech (Chemistry))--Cape Peninsula University of Technology, 2016. / Bimetallic silver-platinum (Ag-Pt) nanoparticles (NPs) were synthesized via simultaneous reduction of varying mole fractions of metal precursors H2PtCl6.6H2O and AgNO3 by sodium citrate. Kinetics rates of were as follows; Ag NPs (0.079 s-1), Ag-Pt NPs 1:1 (0.082 s-1) and Pt NPs (0.006 s-1). The UV visible spectrum of Ag NPs exhibited a characteristic absorption band while Pt NPs and Ag-Pt bimetallic NPs exhibited no absorption peaks. Successful formation of both monometallic and bimetallic NPs was confirmed via transmission electron microscopy (TEM); selected area electron diffraction (SAED) and energy dispersive X-ray (EDX) analysis. TEM images depicted core-shell arrangement in the bimetallic (BM) NP ratios (1:1, 1:3 and 3:1) with an average particle size of 21 nm. The particle size trend where monometallic Ag NPs (60 nm) > Pt NPs (2.5 nm) while in the BM ratios Ag-Pt NPs 1:1 (25 nm) > Ag-Pt NPs 1:3 (20.7 nm). X-ray diffraction (XRD) patterns depicted crystallinity in all the synthesized NPs with confirmation of the face centred cubic structure formation. Transducers were fabricated by drop casting the nanoparticless on the glassy carbon electrode (GCE) and their electrochemical properties studied via cyclic voltammetry (CV). High diffusion coefficient (D) and surface coverage reported were Ag NPs (6.70 cm2 s-1, 54.49 mol cm-2 ) and Ag-Pt NPs 1:1 (0.62 cm2 s-11.85 mol cm-2). Electrochemical band gaps ranged from 1.45 to 1.70 eV while the Tauc’s model band gaps of nanoparticles were found in the range of 2.48 to 3.84 eV. These band gaps were found to be inversely proportional to particle size, which was attributed to the quantum confinement effect. Both optical and electrochemical band gap portrayed similar trend as well as an increase in the BM NP relative to monometallics. These nanoparticles band gaps are within semiconductor range for most materials. The electrochemical behaviour and surface characteristics were studied using 0.1 M PBS solution by scan rates variations for the diffusion coefficient determination of modified electrodes which ranged from 0.62 to 6.10 x 10-5 cm2 s-1. Laviron’s approach for parameters such as apparent charge transfer rate constant, ks, and charge transfer coefficient, α, for electron transfer between NPs and GCE were investigated using CV. The values of electron-transfer coefficients ranged from 0.1 to 0.7 while the charge transfer rate constant values ranged from 0.74 to 31.13 s-1.

The overall purpose of this dissertation was to examine evidence of spillover effects of HIV care and treatment service scale up in sub-Saharan Africa in the past decade. Particularly the focus was to quantify any effect HIV treatment initiation by a person living with HIV (PLHIV) may confer health benefits to the HIV negative population by increasing utilization of non-HIV services or reduce mortality risk. This dissertation had three primary aims. The first aim was to conduct a systematic review of the effect of increasing ART uptake in high HIV prevalence communities on use of non-HIV health services, including maternal, child, in/out-patient, non-HIV laboratory, and TB diagnosis and treatment services. Overall positive effects were found on the majority of health service indicators examined for non-HIV laboratory service utilization and Tuberculosis diagnosis and treatment services. We found negative associations on the majority of indicators examined for child health services. The existing evidence did not point to clear tendencies for maternal health services and outpatient and inpatient services. Restricting the sample to studies with stronger study designs for causal inference, the positive effect on non-HIV laboratory services and the negative impact on child health services held but evidence was mixed for TB diagnosis and treatment services, maternal health services and outpatient and inpatient services. The second aim of this dissertation was to conduct regression discontinuity quasi-experiments to determine whether exposure to health benefits from ART utilization by a person living with HIV (PLHIV) in a household affects uptake of TB, hypertension (HTN) and diabetes mellitus (DM) treatment by other household members with these conditions. The study was conducted in the comprehensive population cohort followed by the Africa Health Research Institute (AHRI) in Kwazulu-Natal (KZN), South Africa. We linked PLHIV engaged in HIV care to their cohabitating household members aged ≥15 years using a unique identifier for homesteads. Household ART utilization significantly increased treatment for diabetes (RR 1.90: 95% CI 1.07-3.40) but not for TB (RR 1.12: 95% CI 0.71-2.03) or hypertension (RR 1.31: 95% CI 0.97-1.77). The third aim of this dissertation was to use the same regression discontinuity design and KZN cohort data as in aim 2 to determine whether exposure to health benefits from ART utilization by PLHIV in a household reduces all-cause mortality of other household members. Overall, household ART utilization did not decrease all-cause mortality (Hazard Ratio (HR) 0.95: 95% CI 0.65-1.4), however, restricting the analysis to a narrow CD4+ cell count range around the regression discontinuity threshold showed reduced all-cause mortality by 67% (HR 0.43: 95% CI 0.22-0.85) among household members of PLHIV on ART; the reduced risk was driven largely by the significant reduction noted among female household members (HR 0.21: 95% 0.08, 0.56).

Introduction APOBEC3G and other related cellular cytosine deaminase family members have potent antiviral activity. In the absence of HIV-1 Vif, APOBEC3G mutates the viral DNA during viral reverse transcription. Our knowledge of the Vif-APOBEC3G interaction in human populations infected with subtype C HIV-1 is limited. Investigation of interactions between HIV and its host is crucial as it can ultimately be exploited in vaccine and therapy design. We hypothesised that certain APOBEC3G haplotypes and/or their expression in peripheral blood mononuclear cells of seroconverters affect viral setpoint and CD4+ T cell counts. We also hypothesised that certain APOBEC3G genetic variants are associated with increased frequency of G to A hypermutations during primary HIV-1 infection and that Vif variability influences disease progression and its ability to neutralise APOBEC3G haplotypes. Methods Our South African study cohort consisted of females at high risk for HIV-1 infection and women with known recent HIV-1 infection. We used quantitative real-time PCR to measure APOBEC3G expression in HIV- and HIV+ samples during primary infection. APOBEC3G variants were identified by DNA sequencing and TaqMan Genotyping. The HIV-1env gene was sequenced to assess Env diversity and the extent of APOBEC3G induced hypermutations. Vif variability was assessed by plasma derived clonal Vif sequences (n= 10-20 per patient) and Vif function was assessed by APOBEC3G degradation assays and HIV-1 infectivity assays. Results We found no correlation between APOBEC3G expression levels and plasma viral loads (r=0.053, p=0.596) or CD4+ T cell counts (r=0.030, p=0.762) in 32 seroconverters. However, APOBEC3G expression levels were significantly higher in HIV- individuals compared to HIV+ individuals (p<0.0001) including matched pre- and post-infection samples from the same individuals (n=13, p<0.0001). Twenty five single nucleotide polymorphisms (SNPs) were identified within the APOBEC3G region. SNP 186R/R was associated with significantly higher viral loads (p=0.0097) and decreased CD4+ T cell levels (p=0.0081), indicating that 186R/R has a negative effect on HIV restriction. Overall HIV-1 env sequences contained a higher number of APOBEC3F compared to APOBEC3G-induced hypermutations and the number of APOBEC3F-induced hypermutations correlated negatively with viral load (r= -0.6, p=0.006) and positively with CD4 T cell counts (r=0.6, p=0.004). We cloned and sequenced a total of 392 subtype C Vifs, which showed an interpatient diversity of 6.2% to 19.2% at the amino acid level. Interestingly, Vif sequence comparison showed a strong preference for a Lysine or a Serine at position 36 for APOBEC3G 186R/R and APOBEC3G 186H/H individuals, respectively. Selected natural subtype C Vif alleles had greater ability to counteract wild type APOBEC3G 186H as compared to the APOBEC3G 186R variant as shown by both functional and HIV infectivity assays. Conclusions In conclusion, APOBEC3G expression in peripheral blood mononuclear cells does not correlate with viral loads or CD4+ T cell counts during primary HIV-1 subtype C infection. However, genetic variants of APOBEC3G may affect HIV-1 pathogenesis. Amino acid changes in Vif may influence its anti-APOBEC3 activity. HIV-1 subtype C Vifs may have adapted to counteract the more active wild type APOBEC3G as compared to the less active APOBEC3G 186R variant. These studies have improved our understanding of viral-host interactions in African populations and HIV-1 subtype C infections. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2014.

Indiana University-Purdue University Indianapolis (IUPUI) / Background: The current treatment for HIV/AIDS is called highly active antiretroviral therapy (HAART) and is a combination of anti-HIV reverse transcriptase inhibitors and protease inhibitors. HAART is capable of suppressing HIV replication and subsequently improving the patients’ survival. However, the issues associated with use of HARRT such as the high cost, severe side-effects, and drug resistance have called for development of alternative anti-HIV therapeutic strategies. In this study, we screened several traditional Chinese medicinal herbal extracts for their anti-HIV activities and determined their anti-HIV mechanisms. Methods: Nine traditional Chinese medicinal (TCM) herbal plants and their respective parts derived from Hainan Island, China were extracted using a series of organic solvents, vacuum dried, and dissolved in dimethyl sulfoxide. Initial anti-HIV activity and cytotoxicity of these extracts were evaluated in HIV-infected human CD4+ T lymphocytes Jurkat. Extracts of higher anti-HIV activities and lower cytotoxicity were selected from the initial screening, and further examined for their effects on HIV-1 entry, post-entry, reverse transcriptase, gene transcription and expression using combined virology, cell biology and biochemistry techniques. Results: Four extracts derived from two different herbal plants completely blocked HIV-1 replication and showed little cytotoxicity at a concentration of 10 g/ml. None of these four extracts had any inhibitory effects on HIV-1 long terminal repeat promoter. Two of them exhibited direct inhibitory activity against HIV-1 reverse transcriptase (RT). All four extracts showed significant blocking of HIV-1 entry into target cells. Conclusions: These results demonstrated that four TCM extracts were capable of preventing HIV-1 infection and replication by blocking viral entry and/or directly inhibiting the RT activity. These results suggest the possibility of developing these extracts as potential anti-HIV therapeutic agents.

No description available.

Despite significant medical advances in HIV treatment, people living with HIV and substance use (PLWH-SU) remain left behind. Compared to people living with HIV (PLWH) without comorbid substance use, PLWH-SU are less likely to engage in medical care and to achieve viral suppression. As a result, PLWH-SU have more frequent preventable hospitalizations, higher rates of viral transmission, and greater morbidity and mortality. Although there is extensive research that explores ways to enhance PLWH-SU’s engagement in HIV care by improving patient-provider interactions, most have focused on the patient, and none have been effective. Grounded in the sociological theory of habitus, this dissertation attended to the medical provider in the patient-provider dyad and aimed to better understand how medical providers’ perceptions and dispositions towards PLWH-SU are formed, and how these perceptions and dispositions are displayed in the ways medical providers interact with and take care of PLWH-SU. Before engaging with habitus, I first conducted a systematic review on how the theory has been used to study medical providers’ clinical practices. Results of the review show that while existing literature has been limited and unclear in its usage of habitus, these studies are informative, and they demonstrate that habitus can be a suitable theoretical foundation for expanding present approaches to research on medical providers’ clinical interactions with PLWH-SU. Following the systematic review, I developed my conceptual framework of medical providers’ treatment habitus (i.e., medical providers’ dispositions towards caring for PLWH-SU) and estimated a typology of treatment habitus using survey data from 258 medical providers in Miami, Florida, Atlanta, Georgia, and the District of Columbia. My analyses show that among this sample of medical providers, there are four types of treatment habitus towards caring for PLWH-SU, and treatment habitus is associated with multi-level factors (e.g., providers’ race, study site, receipt of substance use disorder training). To further explore how medical providers came to develop and how they understand their own treatment habitus, I conducted conversational interviews with 36 medical providers who had completed the abovementioned survey. These interviews revealed medical providers exhibit a spectrum of treatment habitus that is distinguishable by their intentions (person-centered vs. provider-centered) and their methods (informative vs. directive). The interviews also revealed that there are discrepancies in how medical providers spoke about PLWH-SU and how they described their practices towards caring for PLWH-SU. Specifically, although most providers used negative terms to refer to PLWH-SU, the stigmatizing language was almost never accompanied by recollections of stigmatizing behaviors during clinical interactions with PLWH-SU. Taken together, this dissertation expanded on current knowledge about not only how medical providers act when caring for PLWH-SU, but also why they act the ways they do. Findings from this study contribute to an understudied area of HIV and substance use research and provide insights for the development of novel provider-based interventions that can improve the health of this vulnerable and marginalized population.

Aim 1. Accelerated antiretroviral therapy (ART) initiation, including starting ART on the day of HIV diagnosis, has emerged to be one of the approaches to improve ART uptake by shortening or removing some preparatory steps before ART initiation. By doing so, accelerated ART initiation is thought to remove some structural barriers associated with ART initiation process. However, several concerns still need to be addressed, such as whether the expedited process would lead to adverse treatment outcomes after ART initiation. Searched strategy was developed using both MeSH and free text terms relevant to accelerated ART initiation (same-day, immediate, rapid). Exclusion criteria were studies that did not focus on HIV, did not involve HIV treatment, included individuals with HIV aged lower than 12, and contained non-human subjects. Additionally, we excluded articles that were case-reports, qualitative studies, systematic reviews, commentary, points of view, and conference presentations. Four electronic databases (PubMed, Embase, Web of Science, MEDLINE) were used to identify relevant studies published in English between January 2015 and December 2023. Outcomes were retention, viral suppression, pre-ART screening procedures, preferred baseline antiretroviral regimens, additional baseline medications, and adverse events after ART initiation. Two independent researchers were involved in the study selection process. Of 5,455 studies retrieved, 25 studies were included in the review (Cohen’s kappa: 0.88). Six studies reported findings from randomized controlled trials conducted in Lesotho (n=2), Haiti (n=1), South Africa (n=3), and Kenya (n=1), with one study conducted in both South Africa and Keya; 19 studies were observational cohort study from Ethiopia (n=4), West Africa (n=1), Italy (n=2), the United States (n=3), South Africa (n=3), Kenya (n=1), Rwanda (n=1), Sub-Saharan African region (n=1), the United Kingdom (n=1), Turkey (n=1), and China (n=1). The majority of the studies were conducted in urban areas (n=19). Of the 25 included studies, 19 had same-day ART initiation as the intervention or the exposure (three studies measured the time to ART initiation from the day of care engagement, and 16 studies measured it from the day of HIV diagnosis). There was heterogeneity in the pre-ART screening procedures, from relying on symptomatic screening and history assessment to using non-molecular rapid tests to help identify individuals with increased risk of clinical contraindications. Despite this, individuals with symptoms consistent with WHO stage 4 neurological diseases were not eligible for ART. Efavirenz-based ARV was the most regimen reported. The majority of PWH preferred to start ART within 7 days of HIV diagnosis or care engagement (range: 56.5%-86%). Our review suggested mixed results on retention in care and viral suppression after ART initiation, although many studies indicated potential benefits. Despite this, no study reported an association between clinical adverse events, including deaths, and accelerated ART initiation. Our review suggested that accelerated ART initiation can potentially increase ART uptake while not negatively impacting treatment outcomes in some settings. New tools in HIV treatment, such as safer drug regimens and injectable ART, may help improve PWH’s experience and reduce the burden associated with pill burden and frequent clinic visits. Aim 2. Accelerated antiretroviral therapy (ART) initiation has been proposed to address some structural barriers associated with the ART initiation process and improve ART uptake. Despite this, there has yet to be a consensus on how this approach should be implemented, especially concerning the clinical readiness screening procedures. While emerging literature has reported the clinical safety of accelerated ART, limited data are reported from Thailand. Given the heterogeneity of clinical profiles of people with HIV (PWH) in different regions, past studies may not be generalizable to Thailand. Additionally, as different screening procedures affect the time to ART initiation, we need to learn how these procedures impact treatment outcomes. Data were obtained from PWH from 10 ART facilities in six provinces (Chiang Rai, Chiang Mai, Chonburi, Ubon Ratchathani, Songkhla, and Bangkok) in Thailand between July 2017 and July 2019 and followed up until January 2021. All PWH registered in HIV care were included in the analysis, regardless of baseline clinical status. ART facilities were categorized into three models according to the hospital policy on pre-ART laboratory screening procedures: Model A did not consider any lab results at the initiation, Model B considered only CD4 count, and Model C considered other non-CD4 baseline laboratory results. Log-Poisson regression was used to assess the impact of hospital policies on adverse outcomes (deaths, ART discontinuation, loss to follow-up) at months three, six, 12, 18, and 24 after care engagement. Logistic regression was used to examine the impact of hospital policies on viral non-suppression (VNS, HIV-1 RNA>50 copies/mL) at months six, 12, and 18 after ART initiation. Multilevel mixed model was used to account for potential clustering within each hospital policy. Of 10,926 PWH in the dataset, 9,695 (88.7%) were included in this study. Among these, 68% (6,571/9,695), 13% (1,236/9,695), and 19% (1,888/9,695) were in Models A, B, and C, respectively. Both Models A and B had 2 ART facilities each, while Model C had 6 ART facilities. 54.2% (5,257/9,695) self-reported to be men who have sex with men, and the overall baseline median CD4 (IQR) was 168 (129-404) cells/mm3. Compared to Model A, the average risk ratio (95%CI) of adverse events at months three, six, 12, 18, and 24 for Model B was 1.14(1.08-1.20), 1.40(1.31-1.49), 1.19(1.10-1.27), 1.11(1.02-1.21), and 1.32(1.21-1.44), respectively, while it was 1.21(1.16-1.27), 1.76(1.67-1.85), 1.59(1.50-1.67), 1.81(1.71-1.90), and 1.98(1.88-2.10) for Model C, respectively. Of 9,695 PWH, 6,785 (70%) had a confirmed date of ART initiation; 37% (2,513/6,785), 34% (2,332/6,785), and 13% (851/6,785) PWH had information on viral load status at months six, 12, and 24 after ART initiation, respectively. Among these samples, compared to Model A, the average odds ratio (95%CI) of VNS for Model B at months six, 12, and 18 was 0.79(0.59-1.06), 1.06(0.71-1.55), and 1.47(0.49-3.58), respectively, while it was 1.01(0.77-1.32), 0.68(0.40-1.09), and 0.93(0.31-2.22) for Model C, respectively. ART facilities that considered CD4 or any other non-CD4 baseline laboratory results before starting ART had, on average, a higher likelihood of adverse outcomes after the initial care engagement visit and viral non-suppression after ART initiation than ART facilities that did not consider any baseline laboratory result. Aim 3. Clinical screening and psychosocial readiness assessments prior to antiretroviral therapy (ART) initiation are imperative to ensure clinical safety and ART adherence among people with HIV (PWH). However, multiple preparation steps and long wait times associated with ART initiation can contribute to HIV care disengagement and low ART uptake. To address some of the barriers associated with lengthy assessment process, accelerated ART initiation, an approach to start ART on or near the day of HIV diagnosis, has been proposed. Despite this, concerns with the expedited preparation process remain, especially with the PWH’s readiness to have optimal HIV care adherence. This study examined the impact of time to ART initiation on adverse outcomes after care engagement and viral non-suppression (VNS) after ART initiation among PWH in Thailand. Data were obtained from PWH from 10 ART facilities in 6 provinces (Chiang Rai, Chiang Mai, Chonburi, Ubon Ratchathani, Songkhla, and Bangkok) in Thailand between July 2017 and July 2019 and followed up until January 2021. PWH who tested negative for cryptococcal antigen test at baseline and had a confirmed date of ART initiation were included in the analysis and were categorized into three groups based on the time interval between care engagement (defined as the day that PWH first registered at an ART facility) and ART initiation: (1) same day (ART initiation upon the day of care engagement or same day), (2) 1-7 days, and (3) more than 7 days. Log-Poisson regression was used to assess the impact of time to ART initiation on adverse outcomes (deaths, ART discontinuation, and loss to follow-up) at months three, six, 12, 18, and 14 after care engagement. Logistic regression was used to examine the impact of time to ART initiation on VNS (HIV-1 RNA>50 copies/mL) after ART initiation at months six, 12, and 18 after ART initiation. Age, population, hospital policy on pre-ART screening procedures, and baseline CD4 were adjusted in the final models. Of 10,926 PWH in the dataset, 5,528 (50.6%) had complete information on the date of care engagement, negative results for the cryptococcal antigen test, and the date of ART initiation. Among these, 44.23% (2,445/5,528), 38.69% (2,139/5,528), and 17.08% (944/5,528) started ART on the day of, 1-7 days from, and more than 7 days from HIV care engagement visit, respectively. The median age (IQR) was 29 (24-36) and 61% (3,387/5,528) identified themselves as men who have sex with men. The baseline median CD4 (IQR) was 283 (162-412) cells/mm3. Compared to PWH who started ART on the day of HIV care engagement visit, the average risk ratio (RR) of adverse outcomes for those who started ART between 1-7 days at months three, six, 12, 18, and 24 was 0.73(0.60-0.89), 0.66(0.55-0.79), 0.74(0.63-0.86), 0.83(0.71-0.98), and 0.84(0.70-1.01), respectively, while it was 2.27(1.91-2.71), 2.16(1.85-2.52), 1.70(1.46-1.98), 1.93(1.65-2.25), and 2.83(2.44-3.30) for those who started ART more than 7 days, respectively. In the adjusted models, the associations from both groups became statistically non-significant, except for the more than 7 days at month 24 (adjusted RR:1.08; 95%CI:1.04-1.12). Of 5,528 PWH, 29% (1,616/55,28), 36% (1,967/5,528), and 14% (795/5,528) had information on viral load status at months six, 12, and 18 after ART initiation, respectively. Among these individuals, time to ART initiation was determined to have no impact on VNS in both crude and adjusted models. Accelerated ART initiation has the potential to improve ART uptake while maintaining optimal adherence to HIV care. However, HIV programs should recognize and respond to the diversity of needs among PWH to minimize adverse outcomes following ART initiation.

Introduction. The demand for comprehensive Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) services is greater than the available supply, particularly for the provision of antiretroviral therapy. The resulting bottleneck in service delivery has considerable implications for people living with HIV and for resource management. Aim. The purpose of this research was to investigate loss-to-care and associated variables of adult HIV-infected people who were eligible for antiretroviral therapy, from July 2004 to December 2007 at Sinikithemba HIV Clinic in Durban, KwaZulu-Natal. Methods. An observational descriptive and analytic cohort study design was used. Secondary data sourced from Sinikithemba were collated. All HIV-infected adults, 15 years and older when registered on the TrakCare database, who were eligible for antiretroviral therapy were included in the study. Data were extracted to describe the preparation of HIV infected adults who were eligible for antiretroviral therapy. Variables were first summarised and described before the confirmatory analytic steps were taken to measure associations at the p<0.05 significance level. Results. Of the 10 424 HIV-infected adults registered at Sinikithemba, 5470 (52%) were eligible for antiretroviral therapy from July 2004 to December 2007 and 2979 (54%) of these were lost to care prior to initiating antiretroviral therapy. Six exposure variables were significantly associated with this loss-to-care, (gender, baseline CD4 count, pre-eligibility care, antiretroviral therapy delay, preparation step and waiting time). These variables remained significantly associated with loss-to-care even after controlling for confounding with logistic regression. Discussion and Recommendations. With the rapid scale-up of antiretroviral therapy programmes, the outcome of those people living with HIV lost to care before commencing therapy have not been adequately documented. This large cohort enrolled over three-and-a-half years demonstrates that the loss-to-care prior to initiation of antiretroviral therapy is a significant problem that needs to be further investigated. Focusing retention strategies at the pre-antiretroviral therapy stage of HIV care will improve overall programme outcomes. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2011.