Proton-pump inhibitors (PPIs) are among the most frequently prescribed medications. Community-acquired pneumonia (CAP) is a common cause of morbidity, mortality and healthcare spending. Some studies ...suggest an increased risk of CAP among PPI users. We conducted a systematic review and meta-analysis to determine the association between outpatient PPI therapy and risk of CAP in adults.
We conducted systematic searches of MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Scopus and Web of Science on February 3, 2014. Case-control studies, case-crossover, cohort studies and randomized controlled trials reporting outpatient PPI exposure and CAP diagnosis for patients ≥18 years old were eligible. Our primary outcome was the association between CAP and PPI therapy. A secondary outcome examined the risk of hospitalization for CAP and subgroup analyses evaluated the association between PPI use and CAP among patients of different age groups, by different PPI doses, and by different durations of PPI therapy.
Systematic review of 33 studies was performed, of which 26 studies were included in the meta-analysis. These 26 studies included 226,769 cases of CAP among 6,351,656 participants. We observed a pooled risk of CAP with ambulatory PPI therapy of 1.49 (95% CI 1.16, 1.92; I2 99.2%). This risk was increased during the first month of therapy (OR 2.10; 95% CI 1.39, 3.16), regardless of PPI dose or patient age. PPI therapy also increased risk for hospitalization for CAP (OR 1.61; 95% CI: 1.12, 2.31).
Outpatient PPI use is associated with a 1.5-fold increased risk of CAP, with the highest risk within the first 30 days after initiation of therapy. Providers should be aware of this risk when considering PPI use, especially in cases where alternative regimens may be available or the benefits of PPI use are uncertain.
The 2016 WHO consolidated guidelines on the use of antiretroviral drugs defines HIV virologic failure for low and middle income countries (LMIC) as plasma HIV-RNA ≥ 1000 copies/mL. We evaluated ...virologic failure and predictors in four African countries.
We included HIV-infected participants on a WHO recommended antiretroviral therapy (ART) regimen and enrolled in the African Cohort Study between January 2013 and October 2017. Studied outcomes were virologic failure (plasma HIV-RNA ≥ 1000 copies/mL at the most recent visit), viraemia (plasma HIV-RNA ≥ 50 copies/mL at the most recent visit); and persistent viraemia (plasma HIV-RNA ≥ 50 copies/mL at two consecutive visits). Generalized linear models were used to estimate relative risks with their 95% confidence intervals.
2054 participants were included in this analysis. Viraemia, persistent viraemia and virologic failure were observed in 396 (19.3%), 160 (7.8%) and 184 (9%) participants respectively. Of the participants with persistent viraemia, only 57.5% (92/160) had confirmed virologic failure. In the multivariate analysis, attending clinical care site other than the Uganda sitebeing on 2nd line ART (aRR 1.8, 95% CI 1·28-2·66); other ART combinations not first line and not second line (aRR 3.8, 95% CI 1.18-11.9), a history of fever in the past week (aRR 3.7, 95% CI 1.69-8.05), low CD4 count (aRR 6.9, 95% CI 4.7-10.2) and missing any day of ART (aRR 1·8, 95% CI 1·27-2.57) increased the risk of virologic failure. Being on 2nd line therapy, the site where one receives care and CD4 count < 500 predicted viraemia, persistent viraemia and virologic failure.
In conclusion, these findings demonstrate that HIV-infected patients established on ART for more than six months in the African setting frequently experienced viraemia while continuing to be on ART. The findings also show that being on second line, low CD4 count, missing any day of ART and history of fever in the past week remain important predictors of virologic failure that should trigger intensified adherence counselling especially in the absence of reliable or readily available viral load monitoring. Finally, clinical care sites are different calling for further analyses to elucidate on the unique features of these sites.
Antiretroviral therapy during the earliest stage of acute HIV infection (Fiebig I) might minimize establishment of a latent HIV reservoir and thereby facilitate viremic control after analytical ...treatment interruption. We show that 8 participants, who initiated treatment during Fiebig I and were treated for a median of 2.8 years, all experienced rapid viral load rebound following analytical treatment interruption, indicating that additional strategies are required to control or eradicate HIV.
The real-world impact on viral suppression of switching from non-dolutegravir-based therapy to tenofovir/lamivudine/dolutegravir (TLD) is not thoroughly characterized in Africa. We described the ...virologic consequences of switching regimens in the African Cohort Study (AFRICOS), an observational cohort in Nigeria, Kenya, Uganda, and Tanzania.
Among antiretroviral-experienced people living with HIV (PLWH) in AFRICOS, we compared viral load (VL) nonsuppression (VL ≥ 1000 copies/mL) among those who switched with those who never switched to TLD, restricting to participants who had at least 1 visit with a recorded VL after the countrywide rollout of TLD. We calculated Kaplan-Meier curves and conducted Cox proportional hazards modeling to estimate adjusted hazard ratios and 95% confidence intervals for factors potentially associated with nonsuppression.
As of September 1, 2021, there were 3108 PLWH enrolled. Among 1576 participants who switched to TLD, 1486 (94.3%) remained suppressed after transition, 12 (0.8%) remained unsuppressed, and 38 (2.4%) lost suppression, compared with 652 (82.1%), 75 (9.4%), and 46 (5.8%), respectively, of 797 participants who did not switch ( P < 0.001). After adjustment for sex, age, study site, and self-reported antiretroviral therapy adherence, virally suppressed participants who did not switch to TLD had significantly higher rates of losing viral suppression compared with those who switched (adjusted hazard ratio: 4.26; 95% confidence interval: 2.72 to 6.68).
PLWH transitioning to TLD had higher rates of viral suppression compared with those who remained on other regimens. Even within a highly suppressed population, TLD transition provided significant benefits for achieving or maintaining viral suppression.
The African continent demonstrated decisive leadership throughout its response to the COVID-19 pandemic, leveraging lessons learned from previous outbreaks and acting quickly to limit the impact of ...the SARS-CoV-2 virus. We propose a framework to build on these successes that calls for greater collaboration between African leaders, and greater inclusion of African voices in the global health ecosystem.
HIV pre-exposure prophylaxis (PrEP) significantly reduces the risk of HIV acquisition. However, studies have demonstrated discordance between self-reported measures and biomedical benchmarks of PrEP ...adherence. We estimated the correlation between self-reported PrEP adherence and PrEP biomarkers and explored factors associated with adherence among men who have sex with men (MSM) in Nigeria.
TRUST-PrEP, an open-label, prospective study; conducted in Abuja between April 2018 and May 2019. MSM ≥ 18 years with substantial HIV risk were enrolled. Participants reported PrEP adherence in the last month using a 4-point scale from "poor" to "perfect" and serum samples for PrEP biomarkers were collected at months 3 and 9. Serum tenofovir concentration was measured by liquid chromatography-tandem mass spectrometry and considered protective for adherence if ≥ 4.2 ng/ml. Spearman's rank correlation was used to estimate correlation between self-reported adherence and measured tenofovir levels. Generalized estimating equations with a logit link was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between self-reported adherence and laboratory-measured adherence.
A total of 219 MSM with median age 23 (interquartile range 20-27) years had at least one PrEP biomarker assay. Only 66/219 (30%) had at least one record of protective tenofovir concentration. Correlation between tenofovir and self-reported adherence at 3 and 9 months were 0.1 and 0.02 respectively. Furthermore, 17/219 (8%,) and 49/219 (22%) had serum tenofovir of 4.2-35.4 ng/mL and ≥ 35.5 ng/mL, corresponding to at least 4 and 7 days' PrEP use in a week, respectively. PrEP adherence was higher among participants introduced to PrEP in the clinics compared with communities (aOR: 8.35, 95%CI: 3.24, 21.5) and those with same-sex practices family disclosure (aOR: 3.60 95% CI: 1.73, 7.51).
Self-reported PrEP adherence poorly correlated with biomarkers. Facilitating clinic-based PrEP introduction and disclosure of same-sex practices to family among MSM may improve PrEP adherence.
DICs were strategically situated for easy access and staffed by at least one nurse and a mix of community health workers, including peers within the KP communities. For clients afraid to visit health ...facilities for routine viral load testing, a model was established wherein a nurse would go into the community and draw blood from clients. Peer counsellors and community health workers carried ART and PrEP into the community and dispensed to eligible clients. ...high-level advocacy from funders and diplomatic partners should continue for upholding human rights and equitable healthcare access for all.
Abstract
Background
World Health Organization (WHO) guidelines identify human immunodeficiency virus (HIV) viral load <1000 copies/mL as the goal of antiretroviral therapy (ART). However, the ...clinical implications of viremia below this threshold are unclear in the African context. We examined factors associated with persistent low-level viremia (pLLV) and quantified the risk of subsequent virologic.
Methods
The African Cohort Study enrolled HIV-infected adults at clinics in Uganda, Kenya, Tanzania, and Nigeria, with assessments every 6 months. We evaluated participants prescribed ART for at least 6 months without virologic failure for pLLV. We used multinomial logistic regression to evaluate associations between prespecified factors of interest and 3 levels of pLLV (<200, 200–499, and 500–999 copies/mL). We used Anderson-Gill extended Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for viremia category associations with time to failure.
Results
We included 1511 participants with 4382 person-years of follow-up. PLLV <200 copies/mL was observed at 20% of visits while 2% of visits had pLLV 200–499 and 500–999 copies/mL each, with substantial variation by site. Protease inhibitor–containing ART was associated with increased risk of pLLV. Compared to undetectable viral load, pLLV ≥200 copies/mL doubled the risk of developing virologic failure (pLLV 200–499: HR, 1.81 95% CI, 1.08–3.02); pLLV 500–999: HR, 2.36 95% CI, 1.52–3.67).
Conclusions
Participants with pLLV ≥200 copies/mL were at increased risk of subsequent virologic failure. Optimized HIV care in this setting should target viral suppression <200 copies/mL.
Among HIV-infected participants on antiretroviral therapy enrolled in the African Cohort Study, having persistent low-level viremia >200 copies/mL doubled the risk of developing virologic failure.
Despite declines in new HIV diagnoses both globally and in Kenya, parts of Western Kenya still report high HIV prevalence and incidence. We evaluated HIV prevalence to inform the development of ...policies for strategic and targeted HIV prevention interventions.
Adult participants aged 18-35 years were recruited in Kisumu County and screened for HIV for a prospective HIV incidence cohort. Questionnaires assessed HIV-associated risk behaviors. Participants who tested positive for HIV were disaggregated into groups based on prior knowledge of their HIV status: previously-diagnosed and newly-diagnosed. In separate analyses by prior knowledge, robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for factors potentially associated with a positive HIV test in each group, as compared to participants without HIV.
Of 1059 participants tested for HIV, 196 (18.5%) had a positive HIV test. Among PLWH, 78 (39.8%) were newly diagnosed with HIV at screening. After adjusting for other variables, previously-diagnosed HIV was more common among females than males (PR 2.70, 95%CI 1.69-4.28), but there was no observed sex difference in newly-diagnosed HIV prevalence (PR 1.05, 95%CI 0.65-1.69). Previously-diagnosed HIV was also more common among people reporting consistent use of condoms with primary sexual partners as compared to inconsistent condom use (PR 3.19, 95%CI 2.09-4.86), but newly-diagnosed HIV was not associated with such a difference between consistent and inconsistent condom use (PR 0.73, 95%CI 0.25-2.10).
Prevalence of newly-diagnosed HIV was high, at approximately 8% of participants, and not statistically different between genders, highlighting the need for improved HIV case finding regardless of sex. The higher prevalence of previously-diagnosed HIV in female participants may reflect higher rates of HIV testing through more encounters with the healthcare system. Higher prevalence of consistent condom use amongst those previously-diagnosed suggests behavioral change to reduce HIV transmission, a potential benefit of policies to facilitate earlier HIV diagnosis.
Sub-Saharan Africa (SSA) is disproportionately affected by mpox and HIV. We described epidemiologic trends and clinical experiences in the management of mpox in people living with HIV (PLWH) in ...Nigeria and further examined how the rapidly accumulating body of knowledge from the 2022 global mpox outbreak might be explored to improve mpox care in PLWH in SSA. During the 2017/2018 Nigerian mpox outbreak, we reported that 9/40 (22.5%) hospitalized mpox patients with known HIV status were PLWH. In the 2022 global mpox outbreak, 52% of confirmed mpox cases with known HIV status were PLWH, predominantly sexual and gender minority groups. However, substantial missing data on HIV status of confirmed mpox cases highlights a critical gap in HIV testing as a component of mpox management. Before 2022, sexual activity was not commonly linked to mpox transmission, but this was identified as a major driver of transmission during the 2022 mpox outbreak. Notable sexual history observed in Nigerian mpox patients in 2017/2018 suggests that the contribution of sexual activity in human-to-human mpox transmission might have been underappreciated for years. Our cohort of PLWH with mpox, predominantly individuals with advanced or uncontrolled HIV, were significantly more likely to experience severe mpox manifestations and prolonged disease compared with those without HIV. This contrasts with the generally less remarkable differences in mpox presentation between people with and without HIV in Western countries, an observation that can be at least partially explained by more stable HIV disease. The unavailability of mpox antiviral drugs and vaccines in SSA highlights global inequity in mpox response, which requires an urgent attention. As mpox countermeasures become available in SSA, lessons learned from their use in Western countries could provide important guidance for care providers in SSA. Public health measures to mitigate stigmatization in PLWH with mpox is also critical.
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