Browsing by Subject "antiretroviral therapy"

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    Acceptability of community-based adherence clubs among health facility staff in South Africa: a qualitative study
    (2017) Tshuma, Ndumiso; Mosikare, Ofentse; Yun, Jessica A; Alaba, Olufunke A; Maheedhariah, Meera S; Muloongo, Keith; Nyasulu, Peter S
    Patient retention in care for HIV/AIDS is a critical challenge for antiretroviral treatment programs. Community-based adherence programs (CBAPs) as compared to health care facility-based adherence programs have been considered as one of the options to provide treatment maintenance support for groups of patients on antiretroviral therapy. Such an approach provides a way of enhancing self-management of the patient’s condition. In addition, CBAPs have been implemented to support antiretroviral treatment expansion in resource-limited settings. CBAPs involve 30 patients that are allocated to a group and meet at either a facility or a community venue for less than an hour every 2 or 3 months depending on the supply of medication. Our study aimed to establish perceived challenges in moving adherence clubs from health facilities to communities.
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    A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment
    (Journal of the International AIDS Society, 2015-12-16) Johnson, Leigh F; Dorrington, Rob E; Laubscher, Ria; Hoffmann, Christopher J; Wood, Robin; Fox, Matthew P; Cornell, Morna; Schomaker, Michael; Prozesky, Hans; Tanser, Frank; Davies, Mary-Ann; Boulle, Andrew
    Introduction: There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Methods: Completeness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil ID numbers, and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. Results: After exclusions, 91 548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). Conclusions: South Africa’s civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously-documented improvements in ART mortality over time may be biased if based only on data from patient records.
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    Drug-drug interactions between antiretrovirals and bedaquiline
    (2017) Pandie, Mishal; Coetzee, David
    Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. People living with HIV are particularly susceptible to TB infection, and treatment of HIV-TB co-infection is challenging for multiple reasons, including potential drug-interactions. Drug-resistant TB is difficult to treat and is associated with high treatment failure rates, mainly because the antimycobacterial drugs currently available are ineffective against drug-resistant TB. Bedaquiline is a new antimycobacterial drug which has shown great promise through its excellent efficacy for treating drug-resistant TB. Being a new drug, however, potential drug interactions with antiretrovirals are a major concern. Bedaquiline is metabolized in the liver by an enzyme called cytochrome P450 3A (CYP3A). The antiretrovirals nevirapine, efavirenz, and lopinavir/ritonavir (LPV/r) can affect the activity of this enzyme, and consequently affect the concentration of bedaquiline in the patient's blood. Nevirapine and efavirenz increase the activity of CYP3A, which may result in increased metabolism of bedaquiline, thus decreasing the concentration of bedaquiline, with consequent risk of treatment failure or the further development of drug-resistance. LPV/r inhibits the CYP3A enzyme, which may result in decreased bedaquiline metabolism, thus causing high concentration of bedaquiline in the blood, with consequent risk of toxicity. We conducted a pharmacokinetic study in 43 adult patients with drug-resistant TB to evaluate the drug-interactions between bedaquiline and the antiretrovirals nevirapine and LPV/r. We did serial measurements of the bedaquiline concentration in their plasma over 48 hours, and compared these concentrations in patients who were on antiretroviral and those who were not on antiretrovirals. Our results showed that nevirapine had no significant effect on bedaquiline concentrations, while patients on LPV/r had bedaquiline concentrations 2 fold higher than patients not on antiretrovirals. We could not determine the clinical significance of this, but recommend that patients receiving LPV/r and bedaquiline in combination must be closely monitored for side-effects.
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    The epidemiology and clinical correlates of HIV-1 co-receptor tropism in non-subtype B infections from India, Uganda and South Africa
    (BioMed Central Ltd, 2012) Ataher, Quazi; Portsmouth, Simon; Napolitano, Laura; Eng, Sybil; Greenacre, Anna; Kambugu, Andrew; Wood, Robin; Badal-Faesen, Sharlaa; Tressler, Randy
    BACKGROUND: The introduction of C-C chemokine receptor type-5 (CCR5) antagonists as antiretroviral therapy has led to the need to study HIV co-receptor tropism in different HIV-1 subtypes and geographical locations. This study was undertaken to evaluate HIV-1 co-receptor tropism in the developing world where non-B subtypes predominate, in order to assess the therapeutic and prophylactic potential of CCR5 antagonists in these regions. METHODS: HIV-1-infected patients were recruited into this prospective, cross-sectional, epidemiologic study from HIV clinics in South Africa, Uganda and India. Patients were infected with subtypes C (South Africa, India) or A or D (Uganda). HIV-1 subtype and co-receptor tropism were determined and analyzed with disease characteristics, including viral load and CD4+ and CD8+ T cell counts. RESULTS: CCR5-tropic (R5) HIV-1 was detected in 96% of treatment-naive (TN) and treatment-experienced (TE) patients in India, 71% of TE South African patients, and 86% (subtype A/A1) and 71% (subtype D) of TN and TE Ugandan patients. Dual/mixed-tropic HIV-1 was found in 4% of Indian, 25% of South African and 13% (subtype A/A1) and 29% (subtype D) of Ugandan patients. Prior antiretroviral treatment was associated with decreased R5 tropism; however, this decrease was less in subtype C from India (TE: 94%, TN: 97%) than in subtypes A (TE: 59%; TN: 91%) and D (TE: 30%; TN: 79%). R5 virus infection in all three subtypes correlated with higher CD4+ count. CONCLUSIONS: R5 HIV-1 was predominant in TN individuals with HIV-1 subtypes C, A, and D and TE individuals with subtypes C and A. Higher CD4+ count correlated with R5 prevalence, while treatment experience was associated with increased non-R5 infection in all subtypes.
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    Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia
    (2022-01-10) Nyemba, Dorothy C.; Kalk, Emma; Vinikoor, Michael J; Madlala, Hlengiwe P; Mubiana-Mbewe, Mwangelwa; Mzumara, Maureen; Moore, Carolyn B; Slogrove, Amy L; Boulle, Andrew; Davies, Mary-Ann; Myer, Landon; Powis, Kathleen
    Background Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. Methods We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6–10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. Results Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6–10 weeks were lower among infants who were HEU vs HU [β = − 0.29 (95% CI: − 0.46, − 0.12) and [β = − 0.42 (95% CI: − 0.68, − 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [β = − 0.28 CI: − 0.50, − 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6–10 weeks, [β = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [β = − 0.30 CI: − 0.59, − 0.01)] at 6 months, without other anthropometric differences at either site. Conclusion Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU.
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    High rate of virological re-suppression among patients failing second-line antiretroviral therapy following enhanced adherence support: A model of care in Khayelitsha, South Africa
    (2013) Garone, D B; Conradie, K; Patten, G; Cornell, M; Goemaere, W; Kunene, J; Kerschberger, B; Ford, N; Boulle, A; Van Cutsem, G
    Objective. To describe and evaluate the outcomes of a support programme for patients with virological failure while receiving second-line antiretroviral therapy (ART) in South Africa.Method. We described a comprehensive medical and counselling patient support programme for patients receiving secondline ART and with two consecutive viral loads (VLs) >1 000 copies/ml. Patients with >3 months follow-up and at least one VL measurement after inclusion in the programme were eligible for analysis.Results. Of 69 patients enrolled in the programme, 40 had at least one follow-up VL and no known drug resistance at enrolment; 27 (68%) of these re-suppressed while remaining on second-line ART following enhanced adherence support. The majority (18/27; 67%) achieved re-suppression within the first 3 months in the programme. Five patients with diagnosed second-line drug resistance achieved viral re-suppression (<400 copies/ml) after being switched to third-line ART. Seven patients (7/40; 18%) did not achieve viral re-suppression after 9 months in the programme: 6 with known adherence problems (4 without drug resistance on genotype) and 1 with a VL <1 000 copies/ml. Overall, 3 patients (4%) died, 3 (4%) were lost to follow-up and 2 (3%) were transferred out.Conclusion. Our experience from a routine programme demonstrates that with targeted adherence support, the majority of patients who were viraemic while receiving second-line ART returned to an undetectable VL within 3 months. By increasing the time receiving second-line ART and decreasing the need for genotypes and/or third-line ART, this intervention may reduce costs.
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    'HIV is like a tsotsi. ARVs are your guns': associations between HIV-disclosure and adherence to antiretroviral treatment among adolescents in South Africa
    (International AIDS Society, 2015) Cluver, Lucie D; Hodes, Rebecca J; Toska, Elona; Kidiad, Khameer K; Orkina, Mark F; Sherrf, Lorraine; Meincka, Franziska
    Objectives: WHO guidelines recommend disclosure to HIV-positive children by school age in order to improve antiretroviral therapy (ART) adherence. However, quantitative evidence remains limited for adolescents. This study examines associations between adolescent knowledge of HIV-positive status and ART-adherence in South Africa. Design: A cross-sectional study of the largest known community-traced sample of HIVpositive adolescents. Six hundred and eighty-four ART-initiated adolescents aged 10–19 years (52% female, 79% perinatally infected) were interviewed. Methods: In a low-resource health district, all adolescents who had ever initiated ART in a stratified sample of 39 health facilities were identified and traced to 150 communities [n ¼ 1102, 351 excluded, 27 deceased, 40 (5.5%) refusals]. Quantitative interviews used standardized questionnaires and clinic records. Quantitative analyses used multivariate logistic regressions, and qualitative analyses used grounded theory for 18 months of interviews, focus groups and participant observations with 64 adolescents, caregivers and healthcare workers. Results: About 36% of adolescents reported past-week ART nonadherence, and 70% of adolescents knew their status. Adherence was associated with fewer opportunistic infection symptoms [odds ratio (OR) 0.55; 95% CI 0.40–0.76]. Adolescent knowledge of HIV-positive status was associated with higher adherence, independently of all cofactors (OR 2.18; 95% CI 1.47–3.24). Among perinatally infected adolescents who knew their status (n ¼ 362/540), disclosure prior to age 12 was associated with higher adherence (OR 2.65; 95% CI 1.34–5.22). Qualitative findings suggested that disclosure was undertaken sensitively in clinical and family settings, but that adults lacked awareness about adolescent understandings of HIV status. Conclusion: Early and full disclosure is strongly associated with improved adherence amongst ART-initiated adolescents. Disclosure may be an essential tool in improving adolescent adherence and reducing mortality and onwards transmission.
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    The impact of reduced drug prices on the cost-effectiveness of HAART in South Africa
    (National Inquiry Services Centre, 2005) Nattrass, Nicoli; Geffen, Nathan
    South Africa has started ‘rolling out’ highly active anti-retroviral therapy (HAART) through the public health sector, but implementation has been slow. Studies have shown that in Africa AIDS prevention may be more cost-effective than providing HAART; such published results provide some support for the South African government’s apparent reluctance to implement a large-scale rapid HAART roll-out. However, previous studies have not linked treatment and prevention plans, and do not, for the most part, consider the potential savings to the public health sector (e.g., fewer hospital admissions) that may arise from the introduction of HAART. The South African costing exercise summarised here avoids both these limitations. It provides an update of earlier work and takes into account the recent decline in antiretroviral drug prices. It shows that once HIV-related hospital costs are included in the calculation, the cost per HIV infection averted is lower in a treatment-plus-prevention intervention scenario than it is in a prevention-only scenario. This suggests that it is economically advantageous to fund a large-scale comprehensive intervention plan and that the constraints for doing so are political. Once human-rights considerations are included, the case for providing HAART is even more compelling.
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    Impact of Unintended pregnancy on HIV viral load outcomes among postpartum women living with HIV in Cape Town, South Africa: clues from postpartum adherence clubs for antiretroviral therapy trial
    (2022) Mwalye, Pumulo Justine; Odayar, Jasantha; Brittain, Kirsty
    Introduction: Postpartum women living with HIV (WLWHIV) on antiretroviral therapy (ART) are at high risk of viraemia. We examined the association between unintended pregnancy and HIV viral load (VL) at 24 months postpartum in Cape Town, South Africa. Methods: Data are from a randomised trial that compared different ART delivery modalities for postpartum women aged at least 18 years who had initiated ART during their most recent pregnancy, had a VL<400 copies/ml in the previous three months, and had no comorbidities necessitating regular clinical follow-up. Pregnancy intentions regarding the most recent pregnancy were self-reported at enrolment into the study. VL was measured at 24 months postpartum, with elevated VL defined as VL≥1000 copies/ml. Chi-squared tests and logistic regression were used to examine predictors of unintended pregnancy. The impact of unintended pregnancy on elevated VL was examined using Poisson regression models. Results: Among 411 women included in the analysis (mean age: 28.7 years, 42% married/cohabiting, 75% with a parity≥2, and 86% with a VL<50 copies/ml), 57% reported that their most recent pregnancy was unintended. Compared to women aged 18-24 years, older women had a lower relative odds of unintended pregnancy [25-28 years, adjusted odds ratio (AOR): 0.34; 95% confidence interval (CI): 0.17-0.70; 29-34 years, AOR: 0.18; CI: 0.08-0.37; and ≥35 years, AOR: 0.35; CI: 0.14-0.89]. Additionally, unintended pregnancy was associated with being unmarried/not cohabiting (AOR: 4.44; CI: 2.78-7.09) and with higher parity (compared to parity=1: parity=2, AOR: 3.47; 95% CI: 1.86-6.50; and parity≥3, AOR: 6.38; 95% CI: 3.06-13.28). VL data at 24 months postpartum were available for 89% (366/411) of participants of whom 24% had elevated VL≥1000 copies/ml. Unintended pregnancy was associated with elevated VL in unadjusted analyses [risk ratio (RR): 1.54; CI: 1.03-2.28; p=0.032]. After adjustment for maternal factors and trial allocation, the association persisted despite not reaching statistical significance (adjusted risk ratio (aRR): 1.36; CI: 0.88-2.08; p=0.158). Conclusion: Among postpartum WLWHIV in South Africa, unintended pregnancy is prevalent and could be a risk factor for elevated VL. Reproductive health counselling and support during routine care visits may reduce unintended pregnancies and its effects.
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    Incidence and Prevalence Of Renal Dysfunction In Antiretroviral Therapy (ART) Naïve Patients Starting A Tenofovir (TDF) Based ART Regimen In Mitchell's Plain Community Health Centre (CHC) ARV Clinic
    (2021) Fayanju, Olanrewaju Philips; Hellenberg, Derek; Ras, Tasleem
    Background: Tenofovir disoproxil fumarate (TDF) has high antiretrovirus (ARV) activity and available in fixed dose combination (FDC). However, it has been found to cause renal dysfunction. Objectives: To document the prevalence, incidence, pattern of occurence and associated factors of nephrotoxicity in patients initiated on TDF based ART regimen in Mitchell's Plain CHC ARV Clinic and make recommendations. Methodology: The study was conducted by reviewing retrospective records of all ARV naïve HIV positive adults initiated on TDF based ARV regimen from January 2016 to June 2016. The creatinine clearance (CrCl) was calculated from follow up parameters till June 2018. Results: 87 patients were included in the study and 56% were female. The mean age was 34 years. Majority, 83%, had normal renal function at ART initiation. Older age [OR = 1.11; 95% CI (1.03–1.19), p =0.005], was associated with an increased probability of non-normal renal function at baseline. The incidence of CrCl < 90ml/min were 1.5% at 1 month post ARV initiation, 3.3% at 4 months, 6.1% at 12 months and 2.8% at 24 months while the prevalence were 10.5%,11.5%, 20.4% and 16.7% respectively. Older age and male gender were independently associated with prevalence of renal impairment. Conclusion: Renal dysfunction in patients initiated on TDF based regimen in this study varied and were relatively small when compared to the prevalence of renal dysfunction at initiation. Majority of the decline in CrCl were transient and patients were found to have recovered after further follow up. It is recommended that the frequency of renal function monitoring in patients on TDF regimen be done within programmatic guidelines based on patients' risk factors and potential poor outcomes.
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    Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies
    (Lippincott, Williams & Wilkins, 2008) Nash, Denis; Katyal, Monica; Brinkhof, Martin W G; Keiser, Olivia; May, Margaret; Hughes, Rachael; Dabis, Francois; Wood, Robin; Sprinz, Eduardo; Schechter, Mauro; Egger, Matthias
    Background: Few data are available on the long-term immunologic response to ART in resource-limited settings, where antiretroviral therapy (ART) is being scaled up using a public health approach, with a limited repertoire of drugs. Objectives: To describe immunologic response to ART in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. Study population/methodsL: Treatment-naïve patients aged 15 and older from 27 treatment programs were eligible. Multi-level, linear mixed models were used to assess associations between predictor variables and CD4 count trajectories following ART initiation. Results: Of 29,175 patients initiating ART, 8,933 patients (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19,967 patients contributed 39,200 person-years on ART and 71,067 CD4 measurements. The median baseline CD4 count was 114 cells/μL, with 35%<100 cells μL and substantial inter-site variation (range: 61-181 cells/μL). Females had higher median baseline CD4 counts than males (121 vs. 104 cells/μL). The median CD4 count increased from 114 cells/μL at ART initiation to 230 (IQR:144-338) at 6 months, 263 (IQR:175-376) at 1 year, 336 (IQR:224-472) at 2 years, 372 (IQR:242-537) at 3 years, 377 (IQR:221-561) at 4 years, and 395 (IQR:240-592) at 5 years. In multivariable models, baseline CD4 count was the most important determinant of subsequent CD4 count trajectories. Conclusions: These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.
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    Perceived adherence barriers among patients failing second-line antiretroviral therapy in Khayelitsha, South Africa
    (2013) Barnett, W; Patten, G; Kerschberger, B; Conradie, K; Garone, D B; Van Cutsem, G; Colvin, C K J
    Background. The recent scale-up of antiretroviral therapy (ART) coverage in resource-limited settings has greatly improved access to treatment. However, increasing numbers of patients are failing first- and second-line ART.Objective. To examine factors affecting adherence to second-line ART from the perspective of clinic staff and patients, assessing both individual and structural perceived barriers.Methods. Research was conducted at a large primary care tuberculosis (TB)/HIV clinic in Khayelitsha, a peri-urban township in Cape Town, South Africa. Participants were drawn from a Médecins Sans Frontières-run programme to support patients failing second-line ART. A qualitative research approach was used, combining multiple methodologies including key informant interviews with staff (n=11), in-depth interviews with patients (n=10) and a Photovoice workshop (n=11). Responses and photographs were coded by content; data were transformed into variables and analysed accordingly.Results. Staff identified drinking, non-disclosure, not using condoms and pill fatigue as barriers to ART adherence, while patients identified side-effects, not using condoms and a lack of understanding concerning medication timing. With respect to service delivery, staff identified a need for continued counselling and educational support following ART initiation. Patients were concerned about missing medical records and poor staff attitudes in the clinic.Conclusion. These findings identify discrepancies between provider and patient perceptions of barriers to, and facilitators of adherence, as well as of service delivery solutions. This highlights the need for on-going counselling and education following ART initiation, improved quality of counselling, and improved methods to identify and address specific barriers concerning medication adherence.
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    The prevalence of hearing loss in HIV-infected South African adolescents on antiretroviral therapy
    (2017) Banga, Agatha Tafadzwa; Myer, Landon
    Objective: To investigate hearing loss among perinatally HIV-infected (PHIV+) adolescents on antiretroviral therapy (ART), and HIV-non-infected (HIV-) adolescents in Cape Town, South Africa. Methods: A cross-sectional analysis was carried out to describe the prevalence, nature and predictors (demographic, past medical history, clinical findings) of hearing loss in adolescents between 9 and 14 years of age. Screening pure-tone air-conduction (AC) thresholds above 30 decibels (dB) were considered to be indicative of debilitating hearing loss. Statistical analysis included univariate analysis and multivariate logistic regression. Results: The cross-sectional analysis included data from 540 participants; consisting 273 males (51%), 267 females, 432 PHIV+ and 108 HIV-, with a median age of 12 years. Hearing impairment was observed in 19% of all the adolescents in the study. Multivariate analysis showed the following predictors for any hearing loss: an unmarried primary caregiver (odds ratio (OR) 0.59; 95% confidence interval (CI), 0.39;0.91, p = 0.015), being female (OR 1.67; 95% CI, 1.12;2.51; p = 0.013) and reports of being troubled by ear pain or discharge in the last month (OR 2.54; 95% CI, 1.55;4.17; p = <0.001) after adjustment. Univariate analysis showed an association between hearing loss and a longer duration on ART among PHIV+ adolescents (OR 1.80, 95%CI 1.17;2.75, p = 0.007). Conclusion: The prevalence of hearing loss appears to be comparable between PHIV+ and HIVadolescents in Cape Town. In low resource settings, a history of ear pain or discharge within the last month may be used as a screening tool for a hearing assessment, and guide referral for formal hearing tests.
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    Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome
    (Lippincott, Williams & Wilkins, 2010) Meintjes, Graeme; Wilkinson, Robert J; Morroni, Chelsea; Pepper, Dominique J; Rebe, Kevin; Rangaka, Molebogeng X; Oni, Tolu; Maartens, Gary
    Objective: Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of antiretroviral therapy in resource-limited countries. We aimed to assess whether a 4 week course of prednisone would reduce morbidity in patients with paradoxical TB-IRIS without excess adverse events. Design: A randomised double blind placebo-controlled trial of prednisone (1.5mg/kg/day for 2 weeks then 0.75mg/kg/day for 2 weeks). Patients with immediately life-threatening TB-IRIS manifestations were excluded. Methods: The primary combined endpoint was days of hospitalization and outpatient therapeutic procedures, which were counted as one hospital day. Results: 110 participants were enrolled (55 to each arm). The primary combined endpoint was more frequent in the placebo than the prednisone arm (median hospital days 3 (IQR 0-9) and 0 (IQR 0-3) respectively; p=0.04). There were significantly greater improvements in symptoms, Karnofsky score, and quality of life (MOS-HIV) in the prednisone versus the placebo arm at 2 and 4 weeks, but not at later timepoints. Chest radiographs improved significantly more in the prednisone arm at weeks 2 (p=0.002) and 4 (p=0.02). Infections on study medication occurred in more participants in prednisone than placebo arm (27 vs 17 respectively; p=0.05), but there was no difference in severe infections (2 vs 4 respectively; p=0.40). Isolates from 10 participants were found to be resistant to rifampicin after enrollment. Conclusions: Prednisone reduced the need for hospitalisation and therapeutic procedures, and hastened improvements in symptoms, performance and quality of life. It is important to investigate for drug-resistant tuberculosis and other causes for deterioration before administering glucocorticoids.
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    The Prevalence of Antiretroviral-Therapy-related Adverse Reactions, Hospitalisation, and Mortality among People Living with HIV in Africa-A systematic review and Meta-Analysis
    (2022) Moirana, Elizabeth Lorivi; Shung, King Maylene; Hohlfeld, Ameer
    Introduction: Medicines are an important component of any health system. Even though the importance of medicines in the health system is indisputable, one of the major concerns remains the risk of adverse drug reactions when used by consumers. Adverse drug reactions place a burden on the healthcare system, usually as a result of complications requiring hospital admission or extended hospital admissions. In Africa, about 28.6% of adverse drug reactions reported in Africa were due to antiretroviral therapy. Recently, the adoption of the “test and treat” policy by the World Health Organisation increased the number of people receiving antiretroviral therapy. Therefore, this systematic review was conducted to explore the magnitude of antiretroviral therapy-related adverse drug reactions hospitalisations, and mortalities in the region, following the increase in people initiating therapy, and the implications to the service delivery component of the healthcare system. Methods: In March 2021, PubMed, EBSCOHost, and SCOPUS, databases were systematically searched for appropriate articles. The selection of articles was based on predefined inclusion and exclusion criteria. Data from included articles were extracted as per a set of defined criteria into a data extraction form. A meta-analysis was done using Stata package software 15.0 using Stata “metaprop” command. Results: The pooled prevalence of adverse drug reactions hospitalisations in all studies was 26.5% (95% confidence interval:18.4,35.4) and that of mortality was 6.1% (95% confidence interval:2.1,11.7). The most prevalent adverse reactions reported include hepatotoxicity, kidney injury, lactic acidosis, skin, neurologic, and hematologic reactions. The antiviral implicated, are non-nucleoside reverse transcriptase inhibitors, nucleoside/tide reverse transcriptase inhibitors, and protease inhibitors. The pediatric population was underrepresented as only two studies included pediatric patients. The economic impact of adverse reactions was impossible to estimate, as only one study reported on financial implications. Conclusion: Antiretroviral therapy-related adverse reactions hospitalisations and mortalities have a high prevalence in Africa. There are concerns about age-related morbidities and lifestyle diseases as risk factors related to adverse reactions. To adequately combat adverse reactions associated with antiretrovirals, African country health systems need multidisciplinary actions to strengthen strategies for prediction, identification, reporting, and prevention of adverse reaction occurrence.
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    Travel and adherence to antiretroviral therapy among postpartum women living with HIV in South Africa: a cross-sectional study
    (2020) Mvududu, Rufaro; Phillips, Tamsin
    In sub-Saharan Africa, women are disproportionately affected by HIV. Sustained adherence to lifelong antiretroviral therapy (ART) is needed to ensure their own health and prevent transmission of HIV to their partners and their children. However, non-adherence to ART remains a substantial challenge with many associated risk factors. Travel is often reported in the qualitative literature as a barrier to ART adherence among women living with HIV, but few quantitative studies have explored this association. This research aimed to describe travel in the past year among mothers living with HIV in the Long-term Adherence and Care Engagement (LACE) study, to explore factors associated with travel, and to investigate the associations between travel and i) self-reported adherence, and ii) HIV viral load. Part A of this dissertation is the study protocol that introduces the need for this research and presents how the research will be carried out. Part B is a narrative literature review. The review summarises and synthesises existing research relating to HIV treatment and travel in sub-Saharan Africa, giving context to the dissertation. Part C is the journal “ready” manuscript. This section presents an analysis of data from the LACE study, a cross-sectional survey of women living with HIV approximately four years after they had started ART during pregnancy in Gugulethu, Cape Town. At the LACE study visit, data on short-term travel patterns (stayed away from home for 3 or more nights) in the past year and self-reported adherence in the past 30 days (using a validated three-item scale) were collected through structured questionnaires, and a blood specimen was tested for HIV viral load. Poisson regression models with robust standard errors were used to explore factors associated with travel (any versus none), self-reported adherence (100% versus <100%), and viral suppression (≤50 copies/mL). Results were reported as crude risk ratios (RR) and adjusted risk ratios (aRR) with 95% confidence intervals (CI). The results showed that among 353 women enrolled in the LACE study (mean age 32.6 years, 48% employed, 38% married/cohabiting, median 44 months postpartum) 23% (n=81) reported travelling in the past year. Of the women who travelled, most went to the Eastern Cape (90%) and travelled 1-2 times during the year (93%). Women who travelled were more likely to be married/cohabiting than women who had not travelled (aRR = 1.45; 95% Cl: 0.97 - 2.16). Only 9% of women who travelled (7 of 81) reported difficulty with ART adherence due to travel. Overall, 59% of women reported 100% adherence in the past 30 days: 52% of women who had travelled in the past year versus 61% of those who had not travelled (aRR = 0.83; 95% Cl: 0.66-1.04). Only 56% of the cohort were virally suppressed: 60% and 55% of those who had and had not travelled in the past year, respectively (aRR = 1.10; 95% Cl: 0.89-1.36). Travel in the past year was not significantly associated with self-reported adherence or viral suppression in crude or adjusted analyses. These results highlight that poor adherence and viremia were very common in this cohort of women, four years after starting ART in pregnancy. Almost a quarter of women reported travel in the past year but only a v few reported difficulties with adherence related to travel and we found no association between travel in the past year, self-reported adherence in the past 30 days or viremia. Further research is needed to understand adherence patterns during periods of travel and interventions are clearly needed to support women's long-term adherence to ART.