Southern African Journal of Hiv Medicine最新文献

We report a case of dolutegravir resistance in KwaZulu-Natal in a 13-year-old male two years after starting dolutegravir. Resistance most likely developed due to poor adherence as a result of psychosocial issues. This case highlights the importance of the role of the family unit in impacting adherence and close monitoring of treatment-experienced patients with virologic failure following switching to dolutegravir-based regimens.

Background: HIV infection causes immune dysregulation affecting T-cell and monocyte function, which may alter coronavirus disease 2019 (COVID-19) pathophysiology.

Objectives: We investigated the associations among clinical phenotypes, laboratory biomarkers, and hospitalisation outcomes in a cohort of people hospitalised with COVID-19 in a high HIV prevalence area.

Method: We conducted a prospective observational cohort study in Tshwane, South Africa. Respiratory disease severity was quantified using the respiratory oxygenation score. Analysed biomarkers included inflammatory and coagulation biomarkers, CD4 T-cell counts, and HIV-1 viral loads (HIVVL).

Results: The analysis included 558 patients, of whom 21.7% died during admission. The mean age was 54 years. A total of 82 participants were HIV-positive. People living with HIV (PLWH) were younger (mean age 46 years) than HIV-negative people; most were on antiretroviral treatment with a suppressed HIVVL (72%) and the median CD4 count was 159 (interquartile range: 66-397) cells/µL. After adjusting for age, HIV was not associated with increased risk of mortality during hospitalisation (age-adjusted hazard ratio = 1.1, 95% confidence interval: 0.6-2.0). Inflammatory biomarker levels were similar in PLWH and HIV-negative patients. Detectable HIVVL was associated with less severe respiratory disease. In PLWH, mortality was associated with higher levels of inflammatory biomarkers. Opportunistic infections, and other risk factors for severe COVID-19, were common in PLWH who died.

Conclusion: PLWH were not at increased risk of mortality and those with detectable HIVVL had less severe respiratory disease than those with suppressed HIVVL.

What this study adds: This study advances our understanding of severe COVID-19 in PLWH.

Background: The neuropsychiatric side effects of efavirenz occur mainly early during treatment and are usually mild. A lesser-known and serious complication is late-onset efavirenz toxicity causing ataxia and encephalopathy. Data regarding this condition are limited.

Objectives: We describe the clinical picture of late-onset efavirenz toxicity, investigate co-morbidities and report outcomes.

Method: This descriptive study of all patients with late-onset efavirenz toxicity was conducted over three years at Kalafong Provincial Tertiary Hospital, Pretoria, South Africa.

Results: Forty consecutive patients were identified. Mean age was 42.1 years, three patients (7.5%) were male and the mean efavirenz level was 49.0 μg/mL (standard deviation [s.d.]: 24.8). Cerebellar ataxia (82.5%) and encephalopathy (47.5%) were the most common presenting features (40.0% had both); four patients presented with psychosis. Presence of encephalopathy and/or cerebellar ataxia was associated with higher efavirenz levels compared with psychosis (52.1 μg/mL, s.d.: 24.1 vs 25.0 μg/mL, s.d.: 17.1). In most patients, symptoms resolved, but four patients (10.0%) died, and one patient remained ataxic.

Conclusion: Late-onset efavirenz toxicity typically presented with ataxia and encephalopathy, but psychosis can be the presenting feature. The outcome after withdrawal was good, but the mortality of 10.0% is concerning. Recent changes in guidelines favour dolutegravir, but many patients remain on efavirenz, and awareness of the condition is vital.

What this study adds: This large, single-centre study contributes to the limited data of HIV-positive patients with late-onset efavirenz toxicity and emphasises its ongoing relevance in clinical practice.

Background: Dolutegravir, a component of the preferred first-line antiretroviral therapy regimen, has been associated with increased weight gain. South Africa has a high prevalence of obesity, especially among women. Understanding dolutegravir exposure in patients with obesity is important for dose optimisation.

Objectives: We compared the pharmacokinetic parameters of dolutegravir in Southern African adults living with HIV with and without obesity.

Method: Blood samples were collected at various time points over a 24 h-period for dolutegravir assays. Non-compartmental analysis was conducted and geometric mean ratios (GMRs), with 90% confidence intervals (CIs), were generated to compare dolutegravir pharmacokinetic parameters between the groups. Regression analyses to assess predictors of dolutegravir exposure were done.

Results: Forty participants were enrolled, 26 were women and 10 had obesity. Dolutegravir area under the concentration-time curve to 24-h and the maximum concentrations were not statistically significantly lower in participants with obesity: GMR 0.91 (90% CI: 0.71-1.16) and GMR 0.86 (90% CI: 0.68-1.07), respectively. In a multivariate linear regression analysis adjusting for age, gender, body mass index, creatinine clearance and randomisation arm (tenofovir alafenamide or tenofovir disoproxil fumarate), a unit increase in body mass index was associated with 1.2% lower dolutegravir area under the concentration-time curve to 24-h (P = 0.035).

Conclusion: Dolutegravir exposure was marginally lower in participants with obesity, but this is not clinically significant. Our findings suggest that there is no need to dose adjust dolutegravir in people with obesity.

Background: Financial incentivisation has been used to improve all steps of the HIV cascade with varying results. Most studies conducted on the matter are of a quantitative nature, not giving enough space for in-depth understanding as to why financial incentives work or do not work.

Objectives: To describe experiences with, and opinions on, the use of financial incentives to promote linkage to and retention in care from the perspective of people living with HIV.

Method: We performed a qualitative cross-sectional study. In-depth interviews were conducted with adult men and women with HIV accessing health services or research study visits. After codebook development, NVivo 12 software was used to code and analyse the data.

Results: Through the provision of financial incentives, participants were able to cover basic needs. However, some deemed financial incentives as a form of income rather than a nudge to spark interest in changing their health behaviour. Participants communicated that a need for some type of incentive exists and recommended food vouchers as the best possible solution.

Conclusion: Financial incentivisation can facilitate engagement in the HIV care continuum through providing support to people living with HIV.

What this study adds: This study complements the body of research that explores the feasibility of using incentives and which of them may be most beneficial in encouraging patients with HIV to enter into and sustain HIV care.

Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in unique programmatic opportunities to test hypotheses related to the initiation of antiretroviral treatment (ART) and viral load (VL) suppression during a global health crisis, which would not otherwise have been possible.

Objectives: To generate practice-relevant evidence on the impact of initiating ART pre-COVID-19 versus during the COVID-19 pandemic on HIV VL.

Method: Logistic regression was performed on data covering 6596 persons with HIV whose VL data were available, out of 36 585 persons who were initiated on ART between 01 April 2019 and 30 March 2021.

Results: After controlling for covariates such as age, gender, duration on ART, tuberculosis status at the time of the last visit, and rural vs urban status, the odds of having a VL < 1000 copies/mL were significantly higher for clients who started ART during the COVID-19 pandemic than the year before COVID-19 (adjusted odds ratio [AOR]: 2.50; confidence interval [CI]: 1.55-4.01; P < 0.001). Odds of having a VL < 1000 copies/mL were also significantly higher among female participants than male (AOR: 1.23; CI: 1.02-1.48), among patients attending rural clinics compared to those attending urban clinics (AOR: 1.83; CI: 1.47-2.28), and in clients who were 15 years or older at the time of their last visit (AOR: 1.50; CI: 1.07-2.11).

Conclusion: Viral loads did not deteriorate despite pandemic-induced changes in HIV services such as the expansion of multi-month dispensing (MMD), which may have played a protective role regardless of the general negative impacts of response to the COVID-19 crises on communities and individuals.

What this study adds: This research capitalises on the natural experiment of COVID-19-related changes in HIV services and provides new practice-relevant research evidence.

Background: Rapid switching from second-line to third-line antiretroviral therapy (TLART) is crucial for achieving viral suppression and reducing illness related to ART failure.

Objectives: This retrospective cohort study quantified the waiting periods for TLART initiation after virological failure on second-line therapy was detected, assessed factors associated with delays and assessed the outcomes of patients started on TLART.

Method: Data were abstracted from records of individuals eligible for TLART, and the time to TLART initiation was calculated. Reasons for delays were categorised according to patient, clinician and administrative processes.

Results: Fifty-four patients were eligible for TLART. The median delay from the date of first viral load > 1000 copies/mL on second-line therapy to the start of TLART was 640 days (interquartile range [IQR]: 451-983 days). Of the patients that failed second-line and had an application for TLART, 41 (75.6%) were eventually initiated on TLART, and 11 (20.4%) died while waiting. Delays were primarily due to non-response to the first unsuppressed viral load while on second-line ART: 467 days (IQR: 232-803 days).

Conclusion: This study showed a prolonged waiting period for TLART initiation mainly between detected high viral load to requesting of resistance tests; many factors could have contributed, including clinicians' delayed responses to elevated viral loads. Mortality was high before TLART could be initiated. The process of TLART initiation needs to be made more efficient. Healthcare services should be strengthened to (1) recognise and manage virological failure early and identify those eligible for resistance testing, (2) ensure access to resistance testing and appropriately skilled clinicians, and (3) streamline approvals and delivery of TLART.

Background: HIV has been the focus of health systems strengthening in South Africa for the past two decades. Despite progress, sexual and reproductive health (SRH) challenges such as contraception, condom usage and HIV disclosure of young people living with HIV (YPLHIV) remain inadequately addressed. Therefore, the purpose of the study was to describe the SRH needs of YPLHIV and make recommendations to address identified gaps.

Objectives: To explore and describe the SRH needs and potential systemic gaps of YPLHIV with an aim to make recommendations for improvement and contribute to the development of an integrated approach to SRH care in HIV programming.

Method: A quantitative cross-sectional research design with purposive sampling was utilised. YPLHIV were recruited from five healthcare facilities in Gauteng, South Africa, for face-to-face interviews.

Results: One hundred and six YPLHIV with a median age of 18 years were enrolled. A large proportion (57/106; 53.8%) of respondents reported being either single or double orphaned. Sex-related discussions with parents were reported by only 36/106 (34.0%). History of teenage pregnancy was reported in 39/70 (56.0%) of female respondents. A high prevalence of multiple sexual partnerships 41/97 (42.2%) was noted. Consensual partner HIV disclosure was low at 47/97 (48.4%) and the male gender was associated with low 10/35 (28.6%) disclosure of serostatus to sexual partners.

Conclusion: Multiple SRH needs were identified. Interventions are needed to improve parental guidance on SRH issues, increase contraception knowledge and access, and provide better male-centred care.

Background: Adolescents are a unique population with significant unmet health needs. They are often excluded from research that may benefit them as they are perceived as vulnerable and needing protection from research participation. For Research Ethics Committees, conflicting positions in statutes, regulations and ethical guidelines about who provides informed consent for adolescent involvement in health research can be a significant barrier to approving adolescent research. For researchers, the requirement for parental/guardian proxy consent or prolonged approval processes may potentially result in the exclusion of those adolescents most vulnerable and at risk, particularly if issues such as gender-based violence, gender identity, sexuality and sexual practices are in question.

Objectives: To describe the challenges to adolescent research and suggest strategies to address these.

Method: We consider the legal and ethical framework in South Africa regarding the consenting age for adolescents in research, outline the challenges and, using examples of best practices, suggest strategies to address the current conundrum.

Results: We suggest three principles to guide Research Ethics Committees on their approach to reviewing health research involving adolescents. Strategies to develop ethically acceptable approaches to adolescent research and consent processes are described, which include community involvement. We elaborate on examples of nuanced approaches to adolescent research.

Conclusion: The inclusion of adolescents in research is critical in informing appropriate and effective health services for this vulnerable population, whilst providing an opportunity to link them into care and services where relevant.