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Introduction Tuberculosis (TB) is the most important cause of morbidity and mortality among people living with HIV (PLHIV) globally [1,2]. All people with TB should be offered testing for HIV [...], : Background: HIV and tuberculosis are frequently diagnosed concurrently. In March 2021, World Health Organization recommended that antiretroviral therapy (ART) should be started within two weeks of tuberculosis treatment start, at any CD4 count. We assessed whether earlier ART improved outcomes in people with newly diagnosed HIV and tuberculosis. Methods: We did a systematic review by searching nine databases for trials that compared earlier ART to later ART initiation in people with HIV and tuberculosis. We included studies published from database inception to 12 March 2021. We compared ART within four weeks versus ART more than four weeks after TB treatment, and ART within two weeks versus ART between two and eight weeks, and stratified analysis by CD4 count. The main outcome was death; secondary outcomes included IRIS and AIDS?defining events. We pooled effect estimates using random effects meta?analysis. Results and discussion: We screened 2468 abstracts, and identified nine trials. Among people with all CD4 counts, there was no difference in mortality by earlier ART (?4 week) versus later ART (>4 week) (risk difference [RD] 0%, 95% confidence interval [CI] ?2% to +1%). Among people with CD4 count ?50 cells/mm[sup.3] , earlier ART (?4 weeks) reduced risk of death (RD ?6%, ?10% to ?1%). Among people with all CD4 counts earlier ART (?4 weeks) increased the risk of IRIS (RD +6%, 95% CI +2% to +10%) and reduced the incidence of AIDS?defining events (RD ?2%, 95% CI ?4% to 0%). Results were similar when trials were restricted to the four trials which permitted comparison of ART within two weeks to ART between two and eight weeks. Trials were conducted between 2004 and 2014, before recommendations to treat HIV at any CD4 count or to rapidly start ART in people without TB. No trials included children or pregnant women. No trials included integrase inhibitors in ART regimens. Discussion: Earlier ART did not alter risk of death overall among people living with HIV who had TB disease. For logistical and patient preference reasons, earlier ART initiation for everyone with TB and HIV may be preferred to later ART. more...

INTRODUCTION HIV diagnosis is the essential first step for people living with HIV (PLWH) to access HIV care, which can improve health outcomes and reduce the potential for onward transmission [...], : Introduction: HIV diagnosis is the necessary first step towards HIV care initiation, yet many persons living with HIV (PLWH) remain undiagnosed. Employing multiple HIV testing strategies in tandem could increase HIV detection and promote linkage to care. We aimed to assess an intervention to improve HIV detection within socio?sexual networks of PLWH in two sexually transmitted infections (STI) clinics in Lilongwe, Malawi. Methods: We conducted a randomized controlled trial to evaluate an intervention combining acute HIV infection (AHI) screening, contract partner notification and social contact referral versus the Malawian standard of care: serial rapid serological HIV tests and passive partner referral. Enrolment occurred between 2015 and 2019. HIV?seropositive persons (two positive rapid tests) were randomized to the trial arms and HIV?seronegative (one negative rapid test) and ?serodiscordant (one positive test followed by a negative confirmatory test) persons were screened for AHI with HIV RNA testing. Those found to have AHI were offered enrolment into the intervention arm. Our primary outcome of interest was the number of new HIV diagnoses made per index participant within participants? sexual and social networks. We also calculated total persons, sexual partners and PLWH (including those previously diagnosed) referred per index participant. Results: A total of 1230 HIV?seropositive persons were randomized to the control arm, and 561 to the intervention arm. Another 12,713 HIV?seronegative or ?serodiscordant persons underwent AHI screening, resulting in 136 AHI cases, of whom 94 enrolled into the intervention arm. The intervention increased the number of new HIV diagnoses made per index participant versus the control (ratio: 1.9; 95% confidence interval (CI): 1.2 to 3.1). The intervention also increased the numbers of persons (ratio: 2.5; 95% CI: 2.0 to 3.2), sexual partners (ratio: 1.7; 95% CI: 1.4 to 2.0) and PLWH (ratio: 2.3; 95% CI: 1.7 to 3.2) referred per index participant. Conclusions: Combining three distinct HIV testing and referral strategies increased the detection of previously undiagnosed HIV infections within the socio?sexual networks of PLWH seeking STI care. Combination HIV detection strategies that leverage AHI screening and socio?sexual contact networks offer a novel and efficacious approach to increasing HIV status awareness. more...

Depressive disorders are leading contributors to morbidity in low- and middle-income countries and are particularly prevalent among people with non-communicable diseases (NCD). Stressful life events (SLEs) are risk factors for, and can help identify those at risk of, severe depressive illness requiring more aggressive treatment. Yet, research on the impact of SLEs on the trajectory of depressive symptoms among NCD patients indicated for depression treatment is lacking, especially in low resource settings. This study aims to estimate the longitudinal association of SLEs at baseline with depression remission achievement at three, six, and 12 months among adults with either hypertension or diabetes and comorbid depression identified as being eligible for depression treatment. Participants were recruited from 10 NCD clinics in Malawi from May 2019-December 2021. SLEs were measured by the Life Events Survey and depression remission was defined as achieving a Patient Health Questionaire-9 (PHQ-9) score <5 at follow-up. The study population (n = 737) consisted predominately of females aged 50 or higher with primary education and current employment. At baseline, participants reported a mean of 3.5 SLEs in the prior three months with 90% reporting ≥1 SLE. After adjustment, each additional SLE was associated with a lower probability of achieving depression remission at three months (cumulative incidence ratio (CIR) 0.94; 95% confidence interval: 0.90, 0.98, p = 0.002), six months (0.95; 0.92, 0.98, p = 0.002) and 12 months (0.96; 0.94, 0.99, p = 0.011). Re-expressed per 3-unit change, the probability of achieving depression remission at three, six, and 12 months was 0.82, 0.86, and 0.89 times lower per 3 SLEs (the median number of SLEs). Among NCD patients identified as eligible for depression treatment, recent SLEs at baseline were associated with lower probability of achieving depression remission at three, six, and 12 months. Findings suggest that interventions addressing SLEs during integrated NCD and depression care interventions (e.g., teaching and practicing SLE coping strategies) may improve success of depression treatment among adult patient populations in low-resource settings and may help identify those at risk of severe and treatment resistant depression. [ABSTRACT FROM AUTHOR] more...

Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were <1000 copies/mL. Twenty-four cases with dolutegravir resistance among 89 individuals with confirmed virological failure suggests a considerable prevalence in the Malawi HIV program. Successful management of dolutegravir resistance was possible, but early mortality was high. More research on the management of treatment-experienced individuals with dolutegravir resistance is needed. [ABSTRACT FROM AUTHOR] more...

INTRODUCTION Adolescent girls and young women (AGYW) in sub?Saharan Africa are an important population for HIV prevention [1,2]. In Malawi, AGYW ages 15 to 24 have more than twice the [...], : Introduction: As a user?controlled HIV prevention method, oral pre?exposure prophylaxis (PrEP) holds particular promise for adolescent girls and young women (AGYW). HIV prevention cascades, critical frameworks for the design and evaluation of PrEP programmes, outline the priorities of identifying individuals at greatest HIV risk and motivating them to initiate PrEP through perceived HIV risk. To inform future iterations of these cascades and PrEP delivery for AGYW, the objective of this study was to understand the level of interest in PrEP among AGYW at highest HIV risk, and the potential role of perceived risk in motivating PrEP interest. Methods: Using data from a cohort study of HIV?negative AGYW in Lilongwe, Malawi (February 2016 to August 2017), we assessed the relationship between epidemiologic HIV risk (risk index developed in a previous analysis) and PrEP interest, and the extent to which perceived risk explains the relationship between HIV risk and PrEP interest. We further aimed to operationalize the pre?initiation steps of the HIV prevention cascade in the study population. Results: In total, 825 AGYW were included in analyses, of which 43% met the criterion for high epidemiologic HIV risk. While epidemiologic risk scores were positively associated with PrEP interest, high numbers of AGYW both above and below the high?risk cutoff were very interested in PrEP (68% vs. 63%). Perceived risk partially explained the relationship between HIV risk and PrEP interest; greater epidemiologic HIV risk was associated with high perceived risk, which was in turn associated with PrEP interest. Many more high?risk AGYW were interested in PrEP (68%) than expressed a high level of perceived HIV risk (26%). Conclusions: These results highlight key relationships between epidemiologic HIV risk, risk perception and interest in PrEP. While risk perception did partially explain the relationship between epidemiologic risk and PrEP interest, there may be other important motivational mechanisms that are not captured in many HIV prevention cascades. The high number of participants with risk scores below the high?risk cutoff who both expressed high perceived risk and interest in PrEP suggests that demand for PrEP among AGYW may not be well aligned with epidemiologic risk. more...