Reduction in mortality from HIV-related CNS infections in routine care in Africa (DREAMM): a before-and-after, implementation study

Background Four decades into the HIV epidemic, CNS infection remains a leading cause of preventable HIV-related deaths in routine care. The Driving Reduced AIDS-associated Meningo-encephalitis Mortality (DREAMM) project aimed to develop, implement, and evaluate pragmatic implementation interventions and strategies to reduce mortality from HIV-related CNS infection. Methods DREAMM took place in five public hospitals in Cameroon, Malawi, and Tanzania. The main intervention was a stepwise algorithm for HIV-related CNS infections including bedside rapid diagnostic testing and implementation of WHO cryptococcal meningitis guidelines. A health system strengthening approach for hospitals was adopted to deliver quality care through a co-designed education programme, optimised clinical and laboratory pathways, and communities of practice. DREAMM was led and driven by local leadership and divided into three phases: observation (including situational analyses of routine care), training, and implementation. Consecutive adults (aged ≥18 years) living with HIV presenting with a first episode of suspected CNS infection were eligible for recruitment. The primary endpoint was the comparison of 2-week all-cause mortality between observation and implementation phases. This study completed follow-up in September, 2021. The project was registered on ClinicalTrials.gov, NCT03226379. Findings From November, 2016 to April, 2019, 139 eligible participants were enrolled in the observation phase. From Jan 9, 2018, to March 25, 2021, 362 participants were enrolled into the implementation phase. 216 (76%) of 286 participants had advanced HIV disease (209 participants had missing CD4 cell count), and 340 (69%) of 494 participants had exposure to antiretroviral therapy (ART; one participant had missing ART data). In the implementation phase 269 (76%) of 356 participants had a probable CNS infection, 203 (76%) of whom received a confirmed microbiological or radiological diagnosis of CNS infection using existing diagnostic tests and medicines. 63 (49%) of 129 participants died at 2 weeks in the observation phase compared with 63 (24%) of 266 in the implementation phase; and all-cause mortality was lower in the implementation phase when adjusted for site, sex, age, ART exposure (adjusted risk difference –23%, 95% CI –33 to –13; p<0·001). At 10 weeks, 71 (55%) died in the observation phase compared with 103 (39%) in the implementation phase (–13%, –24 to –3; p=0·01). Interpretation DREAMM substantially reduced mortality from HIV-associated CNS infection in resource-limited settings in Africa. DREAMM scale-up is urgently required to reduce deaths in public hospitals and help meet Sustainable Development Goals. Funding European and Developing Countries Clinical Trials Partnership, French Agency for Research on AIDS and Viral Hepatitis. Translations For the French and Portuguese translations of the abstract see Supplementary Materials section

Risks of metabolic syndrome in the ADVANCE and NAMSAL trials

IntroductionThe ADVANCE and NAMSAL trials evaluating antiretroviral drugs have both reported substantial levels of clinical obesity in participants. As one of the main risk factors for metabolic syndrome, growing rates of obesity may drive metabolic syndrome development. This study aims to evaluate the risk of metabolic syndrome in the ADVANCE and NAMSAL trials.MethodsThe number of participants with metabolic syndrome was calculated at baseline and week 192 as central obesity and any of the following two factors: raised triglycerides, reduced HDL-cholesterol, raised blood pressure and raised fasting glucose. Differences between the treatment arms were calculated using the χ2 test.ResultsAcross all visits to week 192, treatment-emergent metabolic syndrome was 15% (TAF/FTC + DTG), 10% (TDF/FTC + DTG) and 7% (TDF/FTC/EFV) in ADVANCE. The results were significantly higher in the TAF/FTC + DTG arm compared to the TDF/FTC/EFV arm (p &lt; 0.001), and the TDF/FTC + DTG vs. the TDF/FTC/EFV arms (p &lt; 0.05) in all patients, and in females. In NAMSAL, the incidence of treatment-emergent metabolic syndrome at any time point was 14% (TDF/3TC + DTG) and 5% (TDF/3TC + EFV) (p &lt; 0.001). This incidence was significantly greater in the TDF/3TC/DTG arm compared to the TDF/3TC/EFV arm in all patients (p &lt; 0.001), and in males (p &lt; 0.001)ConclusionIn this analysis, we highlight treatment-emergent metabolic syndrome associated with dolutegravir, likely driven by obesity. Clinicians initiating or monitoring patients on INSTI-based ART must counsel for lifestyle optimisation to prevent these effects

Adherence to antiretroviral therapy assessed by drug level monitoring and self-report in cameroon

OBJECTIVES: To compare adherence to antiretroviral therapy using drug level monitoring and self-report and to explore the relation between these 2 methods and viral load measurements. METHODS: Sixty patients received a fixed-dose combination of nevirapine, stavudine, and lamivudine in a clinical study in Cameroon. Adherence was assessed every 6 months until month 36 by nevirapine minimal plasma concentration and self-report. Plasma HIV-1 viral load was determined at the same time. Analyses included 159 complete observations. RESULTS: The proportion of patients labeled as "adherent" was significantly lower using nevirapine monitoring (88.7%, 95% confidence interval [CI]: 82.7 to 93.2) than self-report (97.5%, CI: 93.7 to 99.3; P = 0.002). Virologic failure was associated with the nevirapine concentration (adjusted odds ratio [aOR] = 4.43; P = 0.018) but not with the self-reported adherence (aOR = 0.84; P = 0.9). As compared with the virologic outcome, the sensitivity of nevirapine level monitoring for predicting inadequate adherence was 20.5%, the specificity was 91.7%, the positive predictive value was 44.4%, and the negative predictive value was 78.0%. For self-report, the respective values were 2.6%, 97.5%, 25.0%, and 75.5%. CONCLUSIONS: Drug level monitoring provided a more reliable estimate of adherence than self-report. This method could be used in research settings. Operational research is required to define how to improve the accuracy of the self-report method because it is the most feasible method in clinical practice

Antiretroviral Drug Resistance and Routine Therapy, Cameroon

Among 128 patients routinely receiving highly active antiretroviral therapy in an HIV/AIDS outpatient clinic in Cameroon, 16.4% had drug resistance after a median of 10 months. Of these, 12.5% had resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 10.2% to non-NRTIs, and 2.3% to protease inhibitors

Cardiovascular risk and stroke mortality in persons living with HIV: a longitudinal study in a hospital in Yaounde

Introduction:&nbsp;HIV infection is a well-known risk factor for stroke, especially in young adults. In Cameroon, there is a death of data on the outcome of stroke among persons living with HIV (PLWH). This study aimed to assess the cardiovascular risk profile and mortality in PLWH who had a stroke. Methods:&nbsp;this was a retrospective cohort study of all PLWH aged ≥18 years admitted for stroke between January 2010 and December 2019 to the Cardiology Unit of the Yaoundé Central Hospital, Cameroon. Cardiovascular risk was estimated using the modified Framingham score, with subsequent dichotomization into low and intermediate/high risk. Mortality was assessed on day 7 during hospitalization (medical records), at one month, and one year by telephone call to a relative. Results:&nbsp;a total of 43 PLWH who had a stroke were enrolled. Their mean age was 52.1 (standard deviation 12.9) years, most of them were female (69.8%, n = 30). There were 25 (58.1%) patients on concomitant antiretroviral therapy. The Framingham cardiovascular risk score at admission was low in 29 patients (67.4%) and intermediate to high in 14 patients (32.6%). Ischemic stroke was the most common type of stroke in 36 persons (83.7%). The length of hospital stay was 11.4 (interquartile range 9.2-13.7) days. Mortality at 1 year was 46.5% (n = 20). Conclusion:&nbsp;stroke mortality was high in this population of PLWH. Most patients had a low Framingham score, suggesting that this risk estimation tool underestimates cardiovascular risk in PLWH

Инфинитив как средство создания неопределенности в поэтическом тексте

Статья посвящена описанию некоторых особенностей функционирования в поэтическом тексте инфинитивов и их семантике. Инфинитив рассматривается как средство создания неопределенности в поэтическом тексте. Эта состав- ляющая его стилистического потенциала обусловлена лингвистической природой неопределенной формы глагола, что и описывается в данной статье.Стаття присвячена опису певних особливостей функціонування в поетичному тексті інфінітивів і їх семантиці. Інфінітив розглядається як засіб створення неозначеності в поетичному тексті. Ця складова його стилістичного потенціалу обумовлена лінгвістичною природою неозначеної форми дієслова, що й описується в цій статті.The article is devoted to the description of some features of functioning in the poetic text of infinitives and their semantics. An infinitive is examined as a means of creation of uncertainty in a poetic text. This constituent of its stylistic potential is conditioned by the linguistic nature of indefinite form of verb which is under consideration in this article

Determinants of retention in care in an antiretroviral therapy (ART) program in urban Cameroon, 2003-2005

Background: Retention in long-term antiretroviral therapy (ART) program remains a major challenge for effective management of HIV infected people in sub-Saharan Africa. Highly Active Antiretroviral Therapy (ART) discontinuation raises concerns about drug resistance and could negate much of the benefit sought by ART programs. Methods: Based on existing patient records, we assessed determinants of retention in HIV care among HIV patients enrolled in an urban ART at two urban hospitals in Cameroon. Extended Cox regression  procedures were used to identify significant predictors of retention in HIV care. Results: Of 455 patients, 314 (69%) were women, median (IQR) age and baseline CD4 cell count were respectively 36 years (30 – 43) and 110 cells/μL (39 – 177). Forty patients (9%) had active tuberculosis (TB) at enrollment. After a median (IQR) follow-up of 18 months (10–18), 346 (75%) were still in care, 8 (2%) were known dead, and 101 (22%) were lost to follow-up (LFU). Severe immunosuppression (CD4 cell count ≤ 50 cells/μL) at baseline (aHR 2.3; 95% CI 1.4 - 3.7) and active tuberculosis upon enrollment (aHR 1.8; 95% CI 1.0 - 3.6) were independent predictors of cohort losses to follow-up within the first 6 months after HAART initiation. Conclusion: These data suggest that three-quarter of HIV patients initiated on HAART remained in care and on HAART by 18 months; however, those with compromised immunologic status at treatment initiation, and those co-infected with TB were at increased risk for being lost to follow-up within thefirst 6 months on treatment. Keywords: HIV, HAART, low income country, retention in care, loss to follow-up, cohort studies, Cameroon, sub-Sahara Afric