Search

Effectively integrating depression treatment into HIV care in low-resource settings will require substantially investing in program supervision, building and maintaining the capacity of providers, integrating into existing electronic medical records systems, and ensuring the availability of psychotherapy counselors., Key Findings Early evaluations of integrating a depression management program using antidepressants and psychotherapy into HIV clinics in Malawi found that depression screening, diagnosis, and treatment initiation were successfully integrated.A follow-up evaluation found that treatment over time was not delivered as intended, clinic staff had mixed attitudes regarding program acceptability, and the program was not sustained.Antidepressants and problem-solving therapy were acceptable evidence-based depression treatments for patients, but clinic staff found delivering these treatments challenging given constrained human resources and infrastructure.Delivery challenges included difficulties identifying and reassessing patients, negative attitudes, lack of integration into the electronic medical records system, medication stock-outs, staff and space availability, cost of transport, generally low retention, and reliance on study staff. Key Implications Program managers need to invest in program supervision, build and maintain the capacity of providers, integrate into existing electronic medical records systems, and ensure the availability of psychotherapy counselors to more effectively integrate depression treatment into HIV care in these types of settings., Background: Depression is highly prevalent among people living with HIV in Malawi. Depression can undermine engagement in HIV care and worsen HIV morbidity and mortality. The Ministry of Health integrated a pilot depression management program into HIV care at 2 clinics. This program included a measurement-based care protocol for prescribing antidepressants and an adapted Friendship Bench psychotherapy protocol for providing problem solving. Early evaluations indicated successful integration of the initial stages of training and depression screening, diagnosis, and treatment initiation. This follow-up mixed-method investigation contextualizes our previous findings and shares insights from the implementation experience. Methods: We conducted a mixed-methods process evaluation drawing on both patient clinical data and qualitative interviews with patients and clinic staff. We focus on the following implementation outcomes: fidelity, acceptability, and sustainability. Results: Although fidelity to depression screening and treatment initiation was high, fidelity to the follow-up treatment protocol was poor. Antidepressants and problem-solving therapy were acceptable to patients, but clinic staff found delivering treatment challenging given constrained human resources and infrastructure. The program was not sustained after the project. Key identified needs included substantial support to supervise the implementation of the program, continue to build and maintain the capacity of providers, integrate the program into the electronic medical records system, and ensure the availability of Friendship Bench counselors. Conclusions: Although initial steps were successful, sustained integration of this depression treatment program into HIV care in this setting met greater challenges. Implementation science studies that support both implementation and evaluation should recognize the potential for clinical implementers to rely on evaluation staff for clinical support and consider distancing evaluation staff from the actual program implementation. Further research is needed to test enhanced implementation strategies for integrating evidence-based mental health interventions into existing health care systems in a sustainable fashion, particularly in low-resource settings.

Sexually transmitted infections (STIs) remain a public health concern because of their interaction(s) with HIV. In the HPTN 052 study, STIs were evaluated in both HIV-positive index cases and their HIV-negative partners at enrollment and at yearly follow-up visits. Our definition for STI was based on any infection with Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, or Trichomonas vaginalis. We used log-binomial regression models to identify factors associated with prevalent STIs. Generalized estimating equation models with the Poisson distribution were used to compare STI incidence between HIV-positive index cases and HIV-negative partners. 8.1% of the participants had STIs at enrollment. The prevalence of STIs (8.9 vs. 7.2) was higher in HIV-positive index cases than HIV-negative partners. Being female (prevalence ratio (PR) = 1.61; 95% CI: 1.20–2.16) or unmarried (PR = 1.92; 95% CI: 1.17–3.14) was associated with prevalent STIs. Compared to HIV-negative male partners, HIV-positive female index cases had a higher risk of STI acquisition (incidence rate ratio (IRR) = 2.25; 95% CI: 1.70–2.97). While we are implementing HIV prevention interventions for HIV-negative people, we should also intensify targeted STI prevention interventions, especially among HIV-positive women.

Depression is a leading cause of death and disability worldwide, including in low- and middle-income countries (LMICs). Depression often coexists with chronic medical conditions and is associated with worse clinical outcomes. This confluence has led to calls to integrate mental health treatment with chronic disease care systems in LMICs. This article describes the rationale and protocol for a trial comparing the clinical effectiveness and cost-effectiveness of two different intervention packages to implement evidence-based antidepressant management and psychotherapy into chronic noncommunicable disease (NCD) clinics in Malawi.Using constrained randomization, the Sub-Saharan Africa Regional Partnership (SHARP) for mental health capacity building will assign five Malawian NCD clinics to a basic implementation strategy via an internal coordinator, a provider within the chronic care clinic who champions depression services by providing training, supervision, operations, and reporting. Another five clinics will be assigned to depression services implementation via an internal coordinator along with an external quality assurance committee, which will provide a quarterly audit of intervention component delivery with feedback to providers and the health management team.The authors will compare key implementation outcomes (fidelity to intervention), clinical effectiveness outcomes (patient health), and cost-effectiveness and will assess characteristics of clinics that may influence uptake and fidelity.This trial will provide key information to guide the Malawi Ministry of Health in scaling up depression management in existing NCD settings. The SHARP trial is anticipated to substantially contribute to enhancing both mental health treatment and implementation science research capacity in Malawi and the wider region.

Background The prevalence of Human Immunodeficiency Virus (HIV) among prisoners remains high in many countries, especially in Africa, despite a global decrease in HIV incidence. Programs to reach incarcerated populations with HIV services have been implemented in Malawi, but the success of these initiatives is uncertain. We explored which challenges prisoners face in receiving essential HIV services and whether HIV risk behavior is prevalent in prisons. Methods We conducted a mixed-methods (qualitative and quantitative), cross-sectional study in 2018 in six prisons in Southern Malawi, two large central prisons with on-site, non-governmental organization (NGO) supported clinics and 4 smaller rural prisons. Four hundred twelve prisoners were randomly selected and completed a structured questionnaire. We conducted in-depth interviews with 39 prisoners living with HIV, which we recorded, transcribed and translated. We used descriptive statistics and logistic regression to analyze quantitative data and content analysis for qualitative data. Results The majority of prisoners (93.2%) were male, 61.4% were married and 63.1% were incarcerated for 1–5 years. Comprehensive services were reported to be available in the two large, urban prisons. Female prisoners reported having less access to general medical services than males. HIV risk behavior was reported infrequently and was associated with incarceration in urban prisons (adjusted odds ratio [aOR] 18.43; 95% confidence interval [95%-CI] 7.59–44.74; p = p = Conclusions Malawian prisoners reported adequate knowledge about HIV services albeit with gaps in specific areas. Prisoners from smaller, rural prisons had suboptimal access to comprehensive HIV services and female prisoners reported having less access to health care than males. Prisoners have great concern about their poor living conditions affecting general health and adherence to ART. These findings provide guidance for improvement of HIV services and general health care in Malawian institutionalized populations such as prisoners.

PURPOSE OF REVIEW: Evidence of the protective effect of voluntary medical male circumcision (VMMC) against HIV is well established. However, evidence of the protective effect of VMMC against other sexually transmitted infections (STIs) has been inconsistent or scarce across different populations and settings. This review summarizes the current evidence on the effect of VMMC for HIV prevention on acquisition and transmission of other STIs in heterosexual men, women and men who have sex with men (MSM). RECENT FINDINGS: Recent findings continue to strongly support the protective effect of male medical circumcision against acquisition and transmission of herpes simplex virus type 2 (HSV-2), human papillomavirus (HPV) and syphilis infections in heterosexual men and women, and bacterial vaginosis and trichomoniasis in women. There is emerging evidence on the protective effect of VMMC against acquisition of hepatitis B and Mycoplasma genitalium infections in heterosexual men, and HSV-2, HPV and syphilis in MSM. SUMMARY: Evidence on the protective effect of VMMC against acquisition and transmission of common sexually transmitted infections is available for heterosexual men and women but more evidence is required for MSM. This review supports policy recommendations for the protective benefits of VMMC against STIs.

BACKGROUND To assist the Malawi Ministry of Health to evaluate 2 competing strategies for scale-up of isoniazid preventive therapy (IPT) among HIV-positive adults receiving antiretroviral therapy. SETTING Malawi. METHODS We used a multidistrict, compartmental model of the Malawi tuberculosis (TB)/HIV epidemic to compare the anticipated health impacts of 6-month versus continuous IPT programs over a 12-year horizon while respecting a US$10.8 million constraint on drug costs in the first 3 years. RESULTS The 6-month IPT program could be implemented nationwide, whereas the continuous IPT alternative could be introduced in 14 (of the 27) districts. By the end of year 12, the continuous IPT strategy was predicted to avert more TB cases than the 6-month alternative, although not statistically significant (2368 additional cases averted; 95% projection interval [PI], -1459 to 5023). The 6-month strategy required fewer person-years of IPT to avert a case of TB or death than the continuous strategy. For both programs, the mean reductions in TB incidence among people living with HIV by year 12 were expected to be

International audience; Background: Global HIV-1 genetic diversity and evolution form a major challenge to treatment and prevention efforts. An increasing number of distinct HIV-1 recombinants have been identified worldwide, but their contribution to the global epidemic is unknown. We aimed to estimate the global and regional distribution of HIV-1 recombinant forms during 1990-2015.Methods: We assembled a global HIV-1 molecular epidemiology database through a systematic literature review and a global survey. We searched the PubMed, Embase (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) databases for HIV-1 subtyping studies published from Jan 1, 1990, to Dec 31, 2015. Unpublished original HIV-1 subtyping data were collected through a survey among experts in the field who were members of the WHO-UNAIDS Network for HIV Isolation and Characterisation. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. Countries were grouped into 14 regions and analyses were done for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV in each country to generate regional and global estimates of numbers and proportions of HIV-1 recombinants in each time period. The systematic review is registered with PROSPERO, CRD42017067164.Findings: Our global data collection yielded an HIV-1 molecular epidemiology database of 383 519 samples from 116 countries in 1990-2015. We found that the proportion of recombinants increased over time, both globally and in most regions, reaching 22·8% (7 978 517 of 34 921 639) of global HIV-1 infections in 2010-15. Both the proportion and the number of distinct CRFs detected increased over time to 16·7% and 57 CRFs in 2010-15. The global and regional distribution of HIV-1 recombinants was diverse and evolved over time, and we found large regional variation in the numbers (0-44 CRFs), types (58 distinct CRFs), and proportions (0-80·5%) of HIV-1 recombinants. Globally, CRF02_AG was the most prevalent recombinant, accounting for 33·9% (2 701 364 of 7 978 517) of all recombinant infections in 2010-15. URFs accounted for 26·7% (2 131 450 of 7 978 517), CRF01_AE for 23·0% (1 838 433), and other CRFs for 16·4% (1 307 270) of all recombinant infections in 2010-15. Although other CRFs accounted for small proportions of infections globally (

As in other sub-Saharan countries, the burden of depression is high among people living with HIV in Malawi. However, the association between depression at ART initiation and two critical outcomes—retention in HIV care and viral suppression—is not well understood. Prior to the launch of an integrated depression treatment program, adult patients were screened for depression at ART initiation at two clinics in Lilongwe, Malawi. We compared retention in HIV care and viral suppression at 6 months between patients with and without depression at ART initiation using tabular comparison and regression models. The prevalence of depression among this population of adults newly initiating ART was 27%. Those with depression had similar HIV care outcomes at 6 months to those without depression. Retention metrics were generally poor for those with and without depression. However, among those completing viral load testing, nearly all achieved viral suppression. Depression at ART initiation was not associated with either retention or viral suppression. Further investigation of the relationship between depression and HIV is needed to understand the ways depression impacts the different aspects of HIV care engagement.

Background: Early progression of AIDS-associated Kaposi sarcoma (KS-PD) and immune reconstitution inflammatory syndrome (KS-IRIS) sometimes occur after the initiation of antiretroviral therapy (ART). Methods: Early KS-PD and KS-IRIS were assessed in the A5264/AMC-067 trial in which participants with mild-to-moderate AIDS-KS were randomized to initiate ART with either immediate or as-needed oral etoposide. Early KS-PD was defined as tumor progression within 12 weeks of ART initiation. When investigators had concern that early KS-PD was KS-IRIS, additional evaluations were performed. Suspected KS-IRIS was defined as early KS-PD accompanied by a CD4 count increase of ≥50 cells per cubic millimeter or plasma HIV-1 RNA decrease of ≥0.5 log10 copies/mL. Clinical outcome was a composite end point categorized as failure, stable, and response at 48 and 96 weeks compared with baseline. Results: Fifty of 190 participants had early KS-PD (27%): 28 had KS-IRIS and 22 were not evaluated for KS-IRIS. Early KS-PD and KS-IRIS incidences with immediate etoposide versus ART alone were 16% versus 39%, and 7% versus 21%, respectively. Week 48 clinical outcome was 45% failure, 18% stable, and 37% response for no early KS-PD; 82% failure, 2% stable, and 16% response for early KS-PD; and 88% failure, 0% stable, and 12% response for KS-IRIS. Cumulative incidence of KS tumor response by week 96 was 64% for no early KS-PD, 22% with early KS-PD, and 18% with KS-IRIS. Conclusions: Early KS-PD, including suspected KS-IRIS, was common after starting ART for AIDS-KS and was associated with worse long-term clinical outcomes. Starting ART concurrently with etoposide reduced the incidence of both early KS-PD and KS-IRIS compared with ART alone.

Summary Background Long-acting injectable cabotegravir is a novel integrase inhibitor currently in advanced clinical development for HIV prevention and treatment. We aimed to assess the terminal phase pharmacokinetics and safety of long-acting injectable cabotegravir in participants included in the HPTN 077 trial. Methods HPTN 077 was a multicentre, double-blind, randomised, placebo-controlled phase 2a trial done at eight sites in Brazil, Malawi, South Africa, and the USA. Participants (aged 18–65 years), who were HIV-uninfected and at low-risk for HIV, were randomly assigned (3:1) to long-acting injectable cabotegravir (800 mg given three times at 12 week intervals or 600 mg given five times, administered at one 4 week interval, and every 8 weeks thereafter) or placebo. Participants were followed up to 76 weeks after final injection. In a prespecified analysis of secondary and exploratory outcomes, we assessed the safety, measured by the proportion of participants with grade 2 or worse adverse events, and pharmacokinetics, measured by apparent terminal phase half-life (t1/2app) and estimated time to lower limit of quantification (LLOQ) of long-acting injectable cabotegravir during the injection phase (defined as the time between first injection and 12 weeks or 8 weeks after the last injection in cohort 1 or cohort 2 respectively) and tail phase (defined as the time between final injection and 52–76 weeks post-final injection). Safety was analysed in all participants who received at least one injection. Pharmacokinetic analyses included all participants who had received at least one injection and had at least three cabotegravir measurements higher than the LLOQ after the final injection. Pharmacokinetic outcomes were estimated using non-compartmental methods. The trial is completed, and was registered with ClinicalTrials.gov , NCT02178800 . Findings Between Feb 9, 2015, and May 27, 2016, 177 participants (134 participants in the cabotegravir group [74 participants in cohort 1; 60 participants in cohort 2] and 43 participants in the placebo group [25 participants in cohort 1; 18 participants in cohort 2) were enrolled and received at least one injection and thus were included in the safety analysis. The incidence of grade 2 or worse adverse events was significantly lower during the tail phase than the injection phase (p Interpretation The clinical significance of the long pharmacokinetic tail of cabotegravir observed in female participants compared with male participants, and those with higher BMI compared with a lower BMI, need to be addressed in future trials. Funding National Institute of Allergy and Infectious Diseases.

Summary Background Optimal treatment regimens for AIDS-associated Kaposi sarcoma, a frequent contributor to morbidity and mortality among people with HIV, have not been systematically evaluated in low-income and middle-income countries, where the disease is most common. In this study, we aimed to investigate optimal treatment strategies for advanced stage disease in areas of high prevalence and limited resources. Methods In this open-label, non-inferiority trial, we enrolled people with HIV and advanced stage AIDS-associated Kaposi sarcoma attending 11 AIDS Clinical Trials Group sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Eligible participants were randomly assigned (1:1:1) with a centralised computer system to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with antiretroviral therapy (ART; combined efavirenz, tenofovir disoproxil fumarate, and emtricitabine). The primary outcome was progression-free survival (PFS) at week 48, using a 15% non-inferiority margin to compare the investigational groups against the active control group. Safety was assessed in all eligible treated study participants. The study was registered with ClinicalTrials.gov, NCT01435018. Findings 334 participants were enrolled between Oct 1, 2013, and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm, as per the recommendations of the Data and Safety Monitoring Board (DSMB). The etoposide plus ART arm also closed due to inferiority in March, 2016, following a DSMB recommendation. Week-48 PFS rates were higher in the paclitaxel plus ART arm than in both investigational arms. The absolute differences in PFS were −30% (95% CI −52 to −8) for the comparison of paclitaxel plus ART (week 48 PFS 50%, 32 to 67; n=59) and etoposide plus ART (20%, 6 to 33; n=59), and −20% (−33% to −7%) for the comparison of paclitaxel plus ART (64%, 55 to 73; n=138) and bleomycin and vincristine plus ART (44%, 35 to 53; n=132). Both CIs overlapped the non-inferiority margin. The most common adverse events, in 329 eligible participants who began treatment, were neutropenia (48 [15%]), low serum albumin (33 [10%]), weight loss (29 [9%]), and anaemia (28 [9%]), occurring at similar frequency across treatment arms. Interpretation Non-inferiority of either investigational intervention was not shown, with paclitaxel plus ART showing superiority to both oral etoposide plus ART and bleomycin and vincristine plus ART, supporting its use in treating advanced AIDS-associated Kaposi sarcoma in resource-limited settings. Funding US National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health.

OBJECTIVES: Inpatient psychiatric capacity is limited in Malawi and no published studies have assessed psychiatric readmissions there. Information about factors associated with readmission may help guide strategies to reduce readmission rates and keep patients stabilized in the community. Our goal was to determine factors associated with readmission among a cohort of psychiatric inpatients in Lilongwe, Malawi. METHODS: We conducted a retrospective chart review of all patients admitted to an inpatient psychiatric unit in Lilongwe, Malawi from January 1 to December 31, 2011. We used logistic regression to test for associations between readmissions during the study period and patient variables. RESULTS: 419 patients were hospitalized during the study period. 29 patients (6.9%) were readmitted at least once during the study period. Readmission was associated only with intentional medication non-adherence at home (aOR: 3.33, p=0.02). CONCLUSIONS: Intentional medication non-adherence is a potentially modifiable behavioral associated with psychiatric readmission. Efforts to improve medication adherence among patients following hospital discharge may help decrease the risk of readmission.

Background An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) before presentation. There is some evidence suggesting an increased 2-week mortality in those receiving ART for 14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or nonadherence, are not well described. Methods Six hundred seventy-eight adults with a first episode of cryptococcal meningitis recruited into a randomized, noninferiority, multicenter phase 3 trial in 4 Sub-Saharan countries were analyzed to compare clinical presentation and 2- and 10-week mortality outcomes between ART-naïve and -experienced patients and between patients receiving ART for varying durations before presentation. Results Over half (56%; 381/678) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2 weeks (17% vs 20%; hazard ratio [HR], 0.85; 95% CI, 0.6–1.2; P = .35) and 10 weeks (38% vs 36%; HR, 1.03; 95% CI, 0.8–1.32; P = .82) for ART-experienced and ART-naïve patients. Among ART-experienced patients, using different cutoff points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART. Conclusions In this study, there were no significant differences in mortality at 2 and 10 weeks between ART-naïve and -experienced patients and between ART-experienced patients according to duration on ART.

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/mm3, 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.

Tuberculosis (TB) accounts for disproportionate morbidity and mortality among persons living with HIV (PLWH). Conventional methods of TB diagnosis, including smear microscopy and Xpert MTB/RIF, have lower sensitivity in PLWH. Novel high-throughput approaches, such as miRNAomics and metabolomics, may advance our ability to recognize subclinical and difficult-to-diagnose TB, especially in very advanced HIV. We conducted a case-control study leveraging REMEMBER, a multi-country, open-label randomized controlled trial comparing 4-drug empiric standard TB treatment with isoniazid preventive therapy in PLWH initiating antiretroviral therapy (ART) with CD4 cell counts

Female sex workers (FSW) in Malawi have among the highest HIV prevalence estimates worldwide. Daily oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, yet preferences for PrEP delivery among FSW are lacking. Eight focus group discussions, a literature review, and cognitive interviews were conducted to identify modifiable PrEP delivery attributes and inform discrete-choice experiment (DCE) development for FSW in Lilongwe. Enrolled FSW received an interviewer-assisted DCE. Data were analyzed using mixed logit regression. Dispensing location was most preferred, followed by the provision of additional services. Women preferred receiving PrEP at family planning clinics or non-governmental organization run drop-in centers. Cervical cancer screening was the most preferred additional service, while pregnancy testing and partner risk reduction counseling were less valued. This study was the first study to examine PrEP delivery preferences in Malawi using DCE-a powerful elicitation tool to apply to other key populations at risk for HIV.

Pneumonia is the leading cause of death among children globally. Most pneumonia deaths in low-income and middle-income countries (LMICs) occur among children with HIV infection or exposure, severe malnutrition, or hypoxaemia despite antibiotics and oxygen. Non-invasive bubble continuous positive airway pressure (bCPAP) is considered a safe ventilation modality that might improve child pneumonia survival. bCPAP outcomes for high-risk African children with severe pneumonia are unknown. Since most child pneumonia hospitalisations in Africa occur in non-tertiary district hospitals without daily physician oversight, we aimed to examine whether bCPAP improves severe pneumonia mortality in such settings.This open-label, randomised, controlled trial was done in the general paediatric ward of Salima District Hospital, Malawi. We enrolled children aged 1-59 months old with WHO-defined severe pneumonia and either HIV infection or exposure, severe malnutrition, or an oxygen saturation of less than 90%. Children were randomly assigned 1:1 to low-flow nasal cannula oxygen or nasal bCPAP. Non-physicians administered care; the primary outcome was hospital survival. Primary analyses were by intention-to-treat and interim and adverse events analyses per protocol. This trial is registered with ClinicalTrials.gov, number NCT02484183, and is closed.We screened 1712 children for eligibility between June 23, 2015, and March 21, 2018. The data safety and monitoring board stopped the trial for futility after 644 of the intended 900 participants were enrolled. 323 children were randomly assigned to oxygen and 321 to bCPAP. 35 (11%) of 323 children who received oxygen died in hospital, as did 53 (17%) of 321 who received bCPAP (relative risk 1·52; 95% CI 1·02-2·27; p=0·036). 13 oxygen and 17 bCPAP patients lacked hospital outcomes and were considered lost to follow-up. Suspected adverse events related to treatment occurred in 11 (3%) of 321 children receiving bCPAP and 1 (1%) of 323 children receiving oxygen. Four bCPAP and one oxygen group deaths were classified as probable aspiration episodes, one bCPAP death as probable pneumothorax, and six non-death bCPAP events included skin breakdown around the nares.bCPAP treatment in a paediatric ward without daily physician supervision did not reduce hospital mortality among high-risk Malawian children with severe pneumonia, compared with oxygen. The use of bCPAP within certain patient populations and non-intensive care settings might carry risk that was not previously recognised. bCPAP in LMICs needs further evaluation before wider implementation for child pneumonia care.BillMelinda Gates Foundation, International AIDS Society, Health Empowering Humanity.

Background Distal sensory peripheral neuropathy (DSPN) is a complication of human immunodeficiency virus (HIV). We estimate DSPN prevalence in 7 resource-limited settings (RLSs) for combination antiretroviral therapy (cART)–naive people living with HIV (PLWH) compared with matched participants not living with HIV and in PLWH virally suppressed on 1 of 3 cART regimens. Methods PLWH with a CD4+ count Associations between covariates with DSPN at entry were assessed using the χ2 test, and virally suppressed PLWH were assessed using generalized estimating equations. Results Before initiating cART, 21.3% of PLWH had DSPN compared with 8.5% of people not living with HIV (n = 2400; χ2(df = 1) = 96.5; P < .00001). PLWH with DSPN were more likely to report inability to work [χ2(df = 1) = 10.6; P = .001] and depression [χ2(df = 1) = 8.9; P = .003] than PLWH without DSPN. Overall prevalence of DSPN among those virally suppressed on cART decreased: 20.3%, week 48; 15.3%, week 144; and 10.3%, week 192. Incident DSPN was seen in 127 PLWH. Longitudinally, DSPN was more likely in older individuals (P < .001) and PLWH with less education (P = .03). There was no significant association between cART regimen and DSPN. Conclusions Although the prevalence of DSPN decreased following cART initiation in PLWH, further research could identify strategies to prevent or ameliorate residual DSPN after initiating cART in RLSs.

Despite widespread HIV screening and treatment programs across sub-Saharan Africa, many countries are not on course to meet the Joint United Nations Program on HIV/AIDS 90–90–90 targets. As mental health disorders such as depression are prevalent among people living with HIV, investment in understanding and addressing comorbid depression is increasing. This manuscript aims to assess depression and HIV management in sub-Saharan Africa using a 90–90–90 lens through a discussion of: depression and the HIV care continuum; the state of depression screening and treatment; and innovations such as task-shifting strategies for depression management. Due to the lack of mental health infrastructure and human resources, task-shifting approaches that integrate mental health management into existing primary and community health programs are increasingly being piloted and adopted across the region. Greater integration of such mental health care task-shifting into HIV programs will be critical to realizing the 90–90–90 goals and ending the HIV epidemic.

Adherence self-efficacy, belief in one’s ability to adhere to daily medication, is strongly associated with antiretroviral therapy (ART) adherence and preventing mother-to-child HIV transmission. Couple-based interventions could enhance self-efficacy and adherence. We assessed the relationship between couple HIV testing and counseling (cHTC) and adherence self-efficacy using a 100-point culturally-adapted adherence self-efficacy scale (ASES). Secondarily, we explored the relationship between ASES and ART adherence. Ninety HIV-positive pregnant women at an antenatal clinic in Lilongwe, Malawi were enrolled in an observational cohort study. They were assessed with ASES immediately before and one month after receiving cHTC. Median ASES scores were 100 (IQR 95, 100) before and 100 (IQR 99, 100) after cHTC; there was a significant median difference (p = 0.02) for participants before and after cHTC. This change in ASES scores was associated with the odds of self-reported ART adherence in the full population (OR 1.1, p = 0.01), and there was a trend in the same direction for participants with imperfect baseline ASES scores (OR 1.1, p = 0.2). In our population, adherence self-efficacy and ART adherence were both quite high, and those who had room to improve in self-efficacy may have benefited from cHTC, which in turn could impact ART adherence and ultimately mother-to-child transmission.

Clinic transfers among women in Option B+ are frequent, often undocumented, and may lead to suboptimal engagement in care and HIV outcomes. The reasons women move between HIV clinics are not well understood. We conducted four focus group discussions (FGD) among HIV-infected pregnant women in Option B+ and four FGDs and five in-depth interviews among healthcare workers (HCWs) at two large ART clinics in Lilongwe, Malawi. Mobility and fear of inadvertent HIV disclosure, particularly due to seeing neighbors or acquaintances at a clinic, were key drivers of transferring between HIV clinics. Women were aware of the need to obtain a formal transfer, but in practice this was often not feasible and led women to self-transfer clinics. Self-transferring to a new clinic frequently resulted to re-testing and re-initiating ART and concerns about disruptions in ART. Strategies to monitor women's engagement in HIV care without requiring a formal transfer are urgently needed.

Cotrimoxazole preventive therapy may lead to fewer prescriptions., Antimicrobial drug resistance is a serious health hazard driven by overuse. Administration of antimicrobial drugs to HIV-exposed, uninfected infants, a population that is growing and at high risk for infection, is poorly studied. We therefore analyzed factors associated with antibacterial drug administration to HIV-exposed, uninfected infants during their first year of life. Our study population was 2,152 HIV-exposed, uninfected infants enrolled in the Breastfeeding, Antiretrovirals and Nutrition study in Lilongwe, Malawi, during 2004–2010. All infants were breastfed through 28 weeks of age. Antibacterial drugs were prescribed frequently (to 80% of infants), and most (67%) of the 5,329 prescriptions were for respiratory indications. Most commonly prescribed were penicillins (43%) and sulfonamides (23%). Factors associated with lower hazard for antibacterial drug prescription included receipt of cotrimoxazole preventive therapy, receipt of antiretroviral drugs, and increased age. Thus, cotrimoxazole preventive therapy may lead to fewer prescriptions for antibacterial drugs for these infants.

OBJECTIVE To evaluate associations between hair antiretroviral hair concentrations as an objective, cumulative adherence metric, with self-reported adherence and virologic outcomes. DESIGN Analysis of cohort A of the ACTG-A5288 study. These patients in resource-limited settings were failing second-line protease inhibitor-based antiretroviral therapy (ART) but were susceptible to at least one nucleoside reverse transcriptase inhibitor (NRTI) and their protease inhibitor, and continued taking their protease inhibitor-based regimen. METHODS Antiretroviral hair concentrations in participants taking two NRTIs with boosted atazanavir (n = 69) or lopinavir (n = 112) were analyzed at weeks 12, 24, 36 and 48 using liquid-chromatography--tandem-mass-spectrometry assays. Participants' self-reported percentage of doses taken in the previous month; virologic failure was confirmed HIV-1 RNA at least 1000 copies/ml at week 24 or 48. RESULTS From 181 participants with hair samples (61% women, median age: 39 years; CD4+ cell count: 167 cells/μl; HIV-1 RNA: 18 648 copies/ml), 91 (50%) experienced virologic failure at either visit. At 24 weeks, median hair concentrations were 2.95 [interquartile range (IQR) 0.49-4.60] ng/mg for atazanavir, 2.64 (IQR 0.73--7.16) for lopinavir, and 0.44 (IQR 0.11--0.76) for ritonavir. Plasma HIV-1 RNA demonstrated inverse correlations with hair levels (rs -0.46 to -0.74) at weeks 24 and 48. Weaker associations were seen with self-reported adherence (rs -0.03 to -0.24). Decreasing hair concentrations were significantly associated with virologic failure, the hazard ratio (95% CI) for ATV, LPV, and RTV were 0.69 (0.56-0.86), 0.77 (0.68-0.87), and 0.12 (0.06-0.27), respectively. CONCLUSION Protease inhibitor hair concentrations showed stronger associations with subsequent virologic outcomes than self-reported adherence in this cohort. Hair adherence measures could identify individuals at risk of second-line treatment failure in need of interventions.

Among 472 patients with human immunodeficiency virus-associated cryptococcal meningitis, 16% had severe visual loss at presentation, and 46% of these were 4-week survivors and remained severely impaired. Baseline cerebrospinal fluid opening pressure ≥40 cmH2O (adjusted odds ratio [aOR], 2.56; 95% confidence interval [CI], 1.36–4.83; P = .02) and fungal burden >6.0 log10 colonies/mL (aOR, 3.01; 95% CI, 1.58–5.7; P = .003) were independently associated with severe visual loss.

Vaccination is fast becoming a key intervention against the ongoing COVID-19 pandemic. We conducted cross-sectional online surveys to investigate COVID-19 vaccine acceptance across nine Low- and Middle-Income Countries (LMICs, N = 10,183), assuming vaccine effectiveness at 90% and 95%. The prevalence of vaccine acceptance increased from 76.4% (90% effectiveness) to 88.8% (95% effectiveness). Considering a 90% effective vaccine, Malaysia, Thailand, Bangladesh, and five African countries (Democratic Republic of Congo, Benin, Uganda, Malawi, and Mali) had lower acceptance odds compared to Brazil. Individuals who perceived taking the vaccine as important to protect themselves had the highest acceptance odds (aOR 2.49) at 95% effectiveness. Vaccine acceptance was also positively associated with COVID-19 knowledge, worry/fear regarding COVID-19, higher income, younger age, and testing negative for COVID-19. However, chronic disease and female gender&nbsp, reduced the odds for vaccine acceptance. The main reasons underpinning vaccine refusal were fear of side effects (41.2%) and lack of confidence in vaccine effectiveness (15.1%). Further research is needed to identify country-specific reasons for vaccine hesitancy in order to develop mitigation strategies that would ensure high and equitable vaccination coverage across LMICs.

Malawi has the highest invasive cervical cancer (ICC) mortality rate worldwide, and ICC is the leading cause of cancer death among women. In 2004, Malawi adopted visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy. However, screening coverage has remained low (

Introduction Pregnant women living with HIV can achieve viral suppression and prevent HIV mother‐to‐child transmission (MTCT) with timely HIV testing and early ART initiation and maintenance. Although it is recommended that pregnant women undergo HIV testing early in antenatal care in Malawi, many women test positive during breastfeeding because they did not have their HIV status ascertained during pregnancy, or they tested negative during pregnancy but seroconverted postpartum. We sought to estimate the association between the timing of last positive HIV test (during pregnancy vs. breastfeeding) and outcomes of maternal viral suppression and MTCT in Malawi’s PMTCT programme. Methods We conducted a two‐stage cohort study among mother–infant pairs in 30 randomly selected high‐volume health facilities across five nationally representative districts of Malawi between 1 July 2016 and 30 June 2017. Log‐binomial regression was used to estimate prevalence ratios (PR) and risk ratios (RR) for associations between timing of last positive HIV test (i.e. breastfeeding vs. pregnancy) and maternal viral suppression and MTCT, controlling for confounding using inverse probability weighting. Results Of 822 mother–infant pairs who had available information on the timing of the last positive HIV test, 102 mothers (12.4%) had their last positive test during breastfeeding. Women who lived one to two hours (PR = 2.15; 95% CI: 1.29 to 3.58) or >2 hours (PR = 2.36; 95% CI: 1.37 to 4.10) travel time to the nearest health facility were more likely to have had their last positive HIV test during breastfeeding compared to women living

Objectives: Tuberculosis symptoms are very common among people living with HIV (PLHIV) initiating antiretroviral therapy (ART), are not specific for tuberculosis disease and may result in delayed ART start. The risks and benefits of same‐day ART initiation in PLHIV with tuberculosis symptoms are unknown. Methods: We systematically reviewed nine databases on 12 March 2020 to identify studies that investigated same‐day ART initiation among PLHIV with tuberculosis symptoms and reported both their approach to TB screening and clinical outcomes. We extracted and summarized data about TB screening, numbers of people starting same‐day ART and outcomes. Results: We included four studies. Two studies deferred ART for everyone with any tuberculosis symptoms (one or more of cough, fever, night sweats or weight loss) and substantial numbers of people had deferred ART start (28% and 39% did not start same‐day ART). Two studies permitted some people with tuberculosis symptoms to start same‐day ART, and fewer people deferred ART (2% and 16% did not start same‐day). Two of the four studies were conducted sequentially; proven viral load suppression at 8 months was 31% when everyone with tuberculosis symptoms had ART deferred, and 44% when the algorithm was changed so that some people with tuberculosis symptoms could start same‐day ART. Conclusions: Although tuberculosis symptoms are very common in people starting ART, there is insufficient evidence about whether presence of tuberculosis symptoms should lead to ART start being deferred or not. Research to inform clear guidelines would help to maximise the benefits of same‐day ART.

BACKGROUND: Prioritizing HIV prevention for adolescent girls and young women (AGYW) at high risk of HIV acquisition in sub-Saharan Africa (typically considered ≥3 per 100 person years [PYs]) is urgently needed, but identifying these AGYW is challenging. We sought to assess and, if needed, enhance a risk assessment tool from the VOICE trial for identifying AGYW at high risk for HIV in Lilongwe, Malawi. METHODS: A multisite prospective cohort study was conducted among sexually active AGYW 15–24 years old at four health centers in 2016–2017. The VOICE tool was first applied and then updated by excluding variables that were not predictive and adding variables that were. Incidence rates (IR), incidence rate ratios (IRR), ninety-five percent confidence intervals (CIs), area under the receiver-operator characteristic curve (AUC), sensitivity, and specificity were calculated. RESULTS: Seven-hundred ninety-five participants experienced 14 seroconversions over 672 person-years (IR: 2.08 per 100 PYs, CI: 1.23–3.52). The VOICE tool had moderate predictive ability (AUC: 0.64, CI: 0.52, 0.75). Maintaining two variables (genital ulcers and vaginal discharge), removing five socio-demographic variables, and adding two variables (ever pregnant and >5 year male-female age gap) enhanced performance (AUC=0.79, 95% CI: 0.69–0.89). Thirty-five percent had a score of 0, 41% had a score of 1–2, and 24% had a score ≥3. A score ≥1 resulted in 100% sensitivity, 35.9% specificity, and an IR of 3.25 per 100 PYs. A score ≥3 resulted in 64.3% sensitivity, 76.8% specificity, and an IR of 5.89 per 100 PYs. CONCLUSIONS: A simple risk assessment tool identified a subset of AGYW in Malawi at high risk of HIV acquisition who may benefit from biomedical HIV prevention.

BACKGROUND Pregnant and breastfeeding women in Option B+ in Malawi received antiretroviral drugs (ARVs) containing efavirenz (EFV) and tenofovir disoproxil fumarate (TDF). However, effects on growth, renal, bone metabolism, and neurodevelopment of long-term exposure to low doses of these drugs through breast milk in HIV-exposed infants are unclear. METHODS Prospective cohorts of TDF-and-EFV-exposed and TDF-and-EFV-unexposed breastfed infants of HIV-infected and HIV-uninfected mothers in Option B+ were recruited in 2:1 ratio, respectively, followed from birth to 18 months. Infants with low birth weight, premature birth, and congenital abnormalities were excluded. Anthropometrics were assessed at birth, 6 weeks, 3, 6, 12, and 18 months. Neurodevelopment assessments used the Bayley Scales of Infant and Toddler Development III from 6 weeks. Creatinine, alkaline phosphatase, and phosphorus were assessed at 3, 6, and 12 months. RESULTS Of 260 HIV-and-ARV-exposed and 125 HIV-and-ARV-unexposed infants enrolled at birth, 87% and 57%, 78% and 59%, 77% and 54%, 73% and 51%, and 65% and 43% completed 6-weeks, 3, 6, 12, and 18 months visits, respectively. There were no significant differences in the mean Z-scores for length-for-age, weight-for-age, weight-for-length, mid-upper arm circumference-for-age, and head circumference-for-age between groups except at 6-weeks for length-for-age. No bone fractures occurred. Neurodevelopment outcomes were similar between groups. Of creatinine, alkaline phosphatase, and serum phosphate measurements, 1.7%, 2.6%, and 3.3% reached any toxicity levels grades 1-4, respectively, with no differences between groups. CONCLUSION Long-term exposure to EFV and TDF through breastfeeding in infants of HIV-infected mothers does not seem to result in significant growth, neurodevelopment, renal, or bone adverse outcomes. Data support safety of breastfeeding through 18 months within the Option B+ program.

Like in much of Sub-Saharan Africa, descriptive data about psychiatric inpatients and inpatient psychiatric care in Malawi is limited. This study describes the inpatient population at the Bwaila Hospital Psychiatric Unit in Lilongwe, Malawi, as well as treatments received and treatment outcomes. Records of 419 psychiatric inpatients hospitalized from January 1, 2011 to December 31, 2011 were reviewed. Patients were primarily male (73.0%) and were most commonly referred from district hospitals (46.4%). Nearly all patients were involuntarily hospitalized under Malawi's Mental Treatment Act (94.2%). Schizophrenia (30.1%), cannabis use disorder (27.9%) and alcohol use disorder (25.1%) were the most common diagnoses. Suicidal ideation was reported by 4.8% of patients and 2.4% had attempted suicide prior to admission. Homicidal ideation was reported by 7.3% of patients and 5.1% of patients assaulted another patient during their hospitalization. Mean length of stay was 22.1 ± 27.7 days (range: 1.0-243.0). Chlorpromazine (81.3%), diazepam (75.8%), carbamazepine (59.8%) and fluphenazine (56.0%) were the most commonly used medications on the ward. Stabilization and discharge to home was the most common outcome (68.0%), followed by transfer to another hospital (19.5%), discharge against medical advice (8.2%), abscondment (3.4%) and death (1.0%).

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.

ObjectiveTo determine the acceptability of bubble continuous positive airway pressure (bCPAP) and low-flow oxygen among mothers of children who had received either therapy.SettingA district hospital in Salima, Malawi.ParticipantsWe conducted eight focus group discussions (FGDs) with a total of 54 participants. Eligible participants were mothers of children 1 to 59 months of age with severe pneumonia and a comorbidity (HIV-infection, HIV-exposure, malnutrition or hypoxaemia) who, with informed consent, had been enrolled in a randomised clinical trial, CPAP IMPACT (Improving Mortality for Pneumonia in African Children Trial), comparing low-flow oxygen and bCPAP treatments (ClinicalTrials.gov,NCT02484183).Primary and secondary outcome measuresFGDs assessed mothers’ attitudes and feelings towards oxygen and bCPAP before and after therapy along with general community perceptions of respiratory therapies. Data was analysed using inductive thematic analysis to assess themes and subthemes of the transcripts.ResultsCommunity perceptions of oxygen and bCPAP were widely negative. Mothers recounted that they are told that ‘oxygen kills babies’. They are often fearful of allowing their child to receive oxygen therapy and will delay treatment or seek alternative therapies. Mothers report limiting oxygen and bCPAP by intermittently removing the nasal cannulas or mask. After oxygen or bCPAP treatment, regardless of patient outcome, mothers were supportive of the treatment their child received and would recommend it to other mothers.ConclusionThere are significant community misconceptions around oxygen and bCPAP causing mothers to be fearful of either treatment. In order for low-flow oxygen treatment and bCPAP implementation to be effective, widespread community education is necessary.

The Malawi College of Medicine and its partners are building non-communicable diseases’ (NCDs’) research capacity through a grant from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health. Several strategies are being implemented including research mentorship for junior researchers interested to build careers in NCDs’ research. In this article, we present the rationale for and our experiences with this mentorship program over its 2 years of implementation. Lessons learned and the challenges are also shared.

The syndromic management of genital ulcer disease (GUD) misses asymptomatic syphilis cases but is widely utilized in resource-limited settings without diagnostic capabilities to ensure treatment for the most common etiologies of GUD. We used rapid serology tests for syphilis screening at a Malawian sexually transmitted infections clinic. The estimated seroprevalence was 9% and was highest among patients with genital ulcers (26%) and newly diagnosed HIV infection (19%). Rapid syphilis screening has the potential to increase syphilis detection, but accurate patient histories regarding syphilis diagnosis and prior treatment are needed.

In Malawi, 236 participants from the Advancing Cryptococcal Meningitis Treatment for Africa trial were followed for 12 months. The trial outcomes reported at 10 weeks were sustained to 1 year. One-week amphotericin B plus flucytosine was associated with the lowest 1 year mortality (27.5% [95% confidence interval, 16.3 to 44.1]).

Background Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. Methods The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. Results The mean costs per patient were US $847 (95% confidence interval [CI] $776–927) for FLU+5FC, and US $628 (95% CI $557–709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9–41.7%) with FLU+5FC and 53.8% (95% CI 43.1–64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28–208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. Conclusions The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus–infected persons in Africa., The combination of flucytosine plus fluconazole (FLU) is cost-effective, compared with the commonly used regimen of FLU monotherapy, for cryptococcal meningitis treatment in Africa, with an incremental cost-effectiveness ratio of US $65 per life-year saved at the current price.

Objectives: Our primary objective was to compare geometric mean levonorgestrel concentrations between levonorgestrel implant users who were or were not taking the antiretroviral efavirenz, for up to 30 months after implant initiation. Our secondary objective was to evaluate the pregnancy rate among levonorgestrel implant users on efavirenz. Study design: We performed a subanalysis of 42 Malawian women randomized to initiate the levonorgestrel implant as part of a parent randomized clinical trial. Our subset included 30 HIV-infected women taking efavirenz and 12 HIV-uninfected women not taking efavirenz. They underwent urine pregnancy testing every 3 months and serum levonorgestrel testing at day 3 and months 1, 3, 6, 12, 18, 24, 27 and 30 after implant initiation. Geometric mean levonorgestrel concentrations were calculated for efavirenz users and non-efavirenz users at each time point. Results: The geometric mean levonorgestrel concentrations were lower for efavirenz users than non-efavirenz users at every time point; the geometric mean ratio for efavirenz users:non-efavirenz users ranged from 0.60 [90% confidence interval (CI) 0.46–0.79] at 1 month to 0.27 (90% CI 0.12–0.61) at 30 months after implant insertion. No pregnancies occurred over 60 woman-years of concomitant levonorgestrel implant and efavirenz use, although 11 women had levonorgestrel concentrations

Background Depression is highly prevalent among patients newly starting antiretroviral treatment (ART) in Malawi and many other countries. Untreated depression at ART initiation can disrupt the HIV care continuum. Effective approaches for depression screening and treatment exist for low-resource settings, but they are rarely applied. Identifying effective implementation strategies are critical. Methods A pilot program integrated depression screening and treatment into routine HIV care using existing staff at two public health clinics in Malawi in two phases; a screening-only “control” phase and an active “intervention” phase. During the intervention phase, providers prescribed antidepressants or referred patients for Friendship Bench problem-solving therapy. We evaluated the program’s impact on retention in HIV care, viral suppression, and depression remission at 6 months using tabular comparisons and log-binomial models to estimate adjusted risk ratios and mean differences among the intervention group relative to the control group. Results Nearly all consenting participants were screened for depression appropriately and 25% had mild to severe depressive symptoms. During the intervention phase, 86% of participants with mild depressive symptoms started Friendship Bench therapy and 96% of participants with moderate to severe depressive symptoms started antidepressants. Few participants in the intervention group received consistent depression treatment over their first 6 months in care. In the adjusted main analysis, program exposure did not demonstrably affect most HIV or mental health outcomes, though the probability of currently being on ART at 6 months was significantly lower among the intervention group than the control group [RR 0.6(95%CI: 0.4–0.9)]. Conclusions While it is feasible to integrate depression screening and treatment initiation into ART initiation, providing ongoing depression treatment over time is challenging. Similar implementation science studies focused on maintaining depression management will be increasingly important as we strive to understand and test the best ways to implement evidence-based depression treatment within HIV care.

PURPOSE: Studies of factors affecting length of stay during psychiatric hospitalization in sub-Saharan Africa are sparse. A better understanding of such factors may lead to interventions resulting in quicker patient stabilization and discharge, freeing up needed psychiatric beds and reducing health care system expenditures. Therefore, we sought to identify factors associated with long length of stay in Malawi. METHODS: We reviewed the charts of 417 patients hospitalized at Kamuzu Central Hospital’s Bwaila Psychiatric Unit in Lilongwe, Malawi from January 1 to December 31, 2011. Multivariate logistic regression analysis was employed to test for associations between patient factors and long length of stay (defined as more than 28 days) . RESULTS: Mean length of stay was 22.08 ± 27.70 days (range: 0-243). 21.82% (91/417) of patients stayed longer than 28 days. Long length of stay was associated with living outside of Lilongwe district [aOR: 3.65 (1.66-8.01), p=0.001] and treatment for antipsychotic extrapyramidal side effects (EPS) during hospitalization [aOR: 3.45 (1.32-9.03), p=0.012]. Patients who had more interactions with medical providers for this episode of illness prior to presentation at the unit were less likely to have a long length of stay [aOR: 0.35 (0.16-0.76), p=0.008]. CONCLUSIONS: Our findings demonstrate areas of possible intervention to reduce length of stay, including securing means for patient transport home, rapid identification and treatment of EPS, and reducing the risk of EPS by decreased use of high potency first generation antipsychotics.

Our study of human immunodeficiency virus–infected clients attending ART clinics in Lilongwe, Malawi, found that being in a serodiscordant relationship was not associated with dual method contraceptive use at last sex., Background Some human immunodeficiency virus (HIV) serodiscordant couples are faced with the dual challenge of preventing HIV transmission to the uninfected partner and avoiding unintended pregnancy. Therefore, we hypothesized that serodiscordance is associated with dual method use at last sex. Methods We analyzed data from a cross-sectional survey of HIV-infected men and women attending 2 ante-retroviral therapy clinics in Lilongwe, Malawi. We used Fisher exact test and Wilcoxon rank sum to assess for associations between serodiscordance, covariates, and dual method use. Multivariable logistic regression was used to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) of dual method use at last sex, comparing serodiscordant to seroconcordant relationships. Separate analyses were conducted for men and women. Results We surveyed 253 HIV-infected men, of which 44 (17.4%) were in a known serodiscordant relationship and 63 (24.9%) were using dual methods at last sex. Likewise, among 302 HIV-infected women surveyed, 57 (18.9%) were in a known serodiscordant relationship, and 80 (26.5%) were using dual method at last sex. Serodiscordance was not significantly associated with dual method use at last sex for among HIV-infected men (aOR, 0.62; 95% CI, 0.27–1.44) or women (aOR, 1.21; 95% CI, 0.59–2.47). Conclusion Dual method use was low among all HIV-infected individuals, irrespective of their partner's HIV status. Given these findings, we recommend greater efforts to encourage HIV providers to counsel their patients about the importance of dual method use to prevent both unintended pregnancy and sexually transmitted infections.

BACKGROUND: AIDS Clinical Trial Group 5199 compared neurological and neuropsychological test performance of human immunodeficiency virus type 1 (HIV-1)–infected participants in resource-limited settings treated with 3 World Health Organization–recommended antiretroviral (ART) regimens. We investigated the impact of tuberculosis (TB) on neurological and neuropsychological outcomes. METHODS: Standardized neurological and neuropsychological examinations were administered every 24 weeks. Generalized estimating equation models assessed the association between TB and neurological/neuropsychological performance. RESULTS: Characteristics of the 860 participants at baseline were as follows: 53% female, 49% African; median age, 34 years; CD4 count, 173 cells/μL; and plasma HIV-1 RNA, 5.0 log copies/mL. At baseline, there were 36 cases of pulmonary, 9 cases of extrapulmonary, and 1 case of central nervous system (CNS) TB. Over the 192 weeks of follow-up, there were 55 observations of pulmonary TB in 52 persons, 26 observations of extrapulmonary TB in 25 persons, and 3 observations of CNS TB in 2 persons. Prevalence of TB decreased with ART initiation and follow-up. Those with TB coinfection had significantly poorer performance on grooved pegboard (P < .001) and fingertapping nondominant hand (P < .01). TB was associated with diffuse CNS disease (P < .05). Furthermore, those with TB had 9.27 times (P < .001) higher odds of reporting decreased quality of life, and had 8.02 times (P = .0005) higher odds of loss of productivity. CONCLUSIONS: TB coinfection was associated with poorer neuropsychological functioning, particularly the fine motor skills, and had a substantial impact on functional ability and quality of life. CLINICAL TRIALS REGISTRATION: NCT00096824.

Background Delivery of quality healthcare in resource-limited settings is an important, understudied public health priority. Thirty-day (early) hospital readmission is often avoidable and an important indicator of healthcare quality. Methods We investigated the prevalence of all-cause early readmission and its associated factors using age and sex adjusted risk ratios (RR) and 95% confidence intervals (CI). A retrospective review of the medical ward database at Kamuzu Central Hospital in Lilongwe, Malawi was conducted between February and December 2013. Results There were 3547 patients with an index admission of which 2776 (74.4%) survived and were eligible for readmission. Among these patients: 49.7% were male, mean age was 39.7 years, 36.1% were HIV-positive, 34.6% were HIV-negative, and 29.3% were HIV-unknown. The prevalence of early hospital readmission was 5.5%. Diagnoses associated with 30-day readmission were HIV-positive status (RR = 2.41; 95% CI: 1.64–3.53) and malaria (RR = 0.45; 95% CI: 0.22–0.91). Other factors associated with readmission were multiple diagnoses (excluding HIV) (RR = 1.52; 95% CI: 1.11–2.06), and prolonged length of stay (≥ 16 days) at the index hospitalization (RR = 3.63; 95% CI: 1.72–7.67). Conclusion Targeting HIV-infected inpatients with multiple diagnoses and longer index hospitalizations may prevent early readmission and improve quality of care.

BACKGROUND Adolescent girls and young women (AGYW) in sub-Saharan Africa have high HIV prevalence and incidence. We sought to understand which HIV risk factors individually and in combination contribute to risk, and whether these factors are associated with HIV worry and risk perception. SETTING This study is ongoing at 4 public health centers in Lilongwe, Malawi (2016-2017). METHODS AGYW of 15-24 years old were recruited to participate in a study assessing 4 models of service delivery. At each health center, participants completed a baseline survey assessing socioeconomic, behavioral, biomedical, and partnership characteristics; self-reported HIV status; and, if HIV-uninfected, HIV risk perception (high versus low or none) and HIV worry (any versus none). We analyzed associations between baseline characteristics and HIV prevalence, risk perception, and worry. RESULTS Among 1000 AGYW, median age was 19 years (IQR: 17-21). Thirty-three participants reported being HIV-infected. Fifteen characteristics were associated with HIV infection. Having more risk factors was associated with higher HIV prevalence (≤4 factors, 0.5%; 5-8 factors, 6%; >8 factors, 21%). Having more risk factors was also associated with higher risk perception (P < 0.001) and higher worry (P < 0.001). However, among those with ≥8 risk factors, 52% did not consider themselves to be at high risk and 21% did not report any HIV worry. CONCLUSIONS Most AGYW perceive little risk of HIV acquisition, even those at highest risk. As a critical gap in the HIV prevention cascade, accurate risk perception is needed to tailor effective and sustained combination prevention strategies for this vulnerable population.

Background Data on the use of seclusion for psychiatric inpatients in sub-Saharan Africa are extremely limited. Though seclusion is sometimes necessary for patients that pose a threat to themselves or others, adverse physical and psychological sequelae from the experience are increasingly being recognized, leading to efforts to reduce its use. The purpose of this study was to calculate the frequency of seclusion in patients hospitalized in an inpatient psychiatric unit in Lilongwe, Malawi, and to identify factors associated with its use. Methods Records of 419 psychiatric inpatients hospitalized at Kamuzu Central Hospital’s Bwaila Psychiatric Unit in Lilongwe, Malawi, from January 1, 2011 to December 31, 2011, were reviewed. Multivariate logistic regression analysis was employed to identify factors associated with the use of seclusion. Results Seclusion was used for 30.3% (127/419) of patients during the study period. Male patients had increased odds of being secluded (aOR: 2.22, p=0.02). Assaulting other patients on the unit (aOR 7.92, p

Background In sub-Saharan Africa, 3 community-facility linkage (CFL) models—Expert Clients, Community Health Workers (CHWs), and Mentor Mothers—have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood. Methods and findings We sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant “poor outcome” (encompassing documented HIV-positive test result, LTFU, or death), in Malawi’s PMTCT/ART program. We sampled 30 of 42 high-volume health facilities (“sites”) in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother–infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother–infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were ≤24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) ≥2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and ≥2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement. Conclusions In this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences., Michael Herce and co-workers study potential improvements in linkage to care for prevention of mother to child transmission of HIV in Malawi., Author summary Why was this study done? Attrition from the prevention of mother-to-child transmission of HIV (PMTCT) continuum threatens health gains for pregnant and breastfeeding women (PBFW) living with HIV and their infants. To improve PMTCT services in Africa, 3 community-facility linkage (CFL) models—Mentor Mothers, Community Health Workers (CHWs), and Expert Clients/Patients—have been widely implemented. Available evidence suggests that these CFL models may improve the health of PBFW living with HIV and their infants. Despite the promise of CFL models, however, no studies from the current “treat all” era have attempted to examine which of these models works best in “real world” PMTCT programs for ensuring maternal HIV care retention and viral suppression and infant HIV-free survival. What did the researchers do and find? We conducted a descriptive study in Malawi by sampling busy health facilities in 5 districts and, at selected facilities, reviewing medical records for all newly HIV-diagnosed PBFW and their HIV-exposed infants. We then administered a survey to a randomly selected subset of these mother–infant pairs to assess CFL model exposure and HIV outcomes. We found that compared to women supported by the most common CFL model, Expert Clients, women supported by CHWs were 13% more likely to start antiretroviral therapy (ART) soon after their HIV diagnosis. Over the 2 years following HIV diagnosis, PBFW living with HIV who received CHW model support spent 14% more time retained on ART and virally suppressed than women in the Expert Client model. Infants receiving Mentor Mother model support were 24% more likely to receive HIV testing by age 6 months than infants supported by Expert Clients. The 12-month infant risk of experiencing a positive HIV test result, loss to follow-up, or death did not vary significantly by CFL model. What do these findings mean? CFL models had widespread coverage in the national PMTCT/ART program in our selected sites in Malawi, reaching most mother–infant pairs. Important differences were noted in maternal and infant HIV outcomes by CFL model. Favorable HIV outcomes were seen in women supported by the CHW model, and higher infant EID testing uptake was observed in infants supported by Mentor Mothers. Although caution should be exercised when applying our findings to other settings, we found that CFL models may have different impacts on maternal and infant HIV outcomes at different steps along the PMTCT continuum in Malawi. Future research should identify the key features of CFL models that drive these outcome differences to better inform PMTCT programming in Malawi.

In order to design effective strategies to eradicate the HIV, an understanding of persistent viral reservoirs is needed. Many studies have demonstrated HIV residual viremia prevalence in high income countries, data from low- and middle-income countries (LMIC) are limited. We assessed the prevalence, and factors associated with residual viremia in people with HIV (PWH), who were virally-suppressed on antiretroviral therapy (ART) in LMIC. We also compared residual viremia prevalence between the LMIC and US.This is a cross-sectional, retrospective study that utilized stored specimen samples from the AIDS clinical trials group (ACTG) studies A5175 and A5208. The last available sample among participants with plasma HIV RNA

We aimed to understand drivers of HIV-infection in pregnant women in Malawi. The study was conducted in antenatal and labor and delivery wards. HIV-infected women and their partners (cases) were frequency matched in a 1:2 ratio based on age and screening location to HIV-uninfected women and their partners (controls) in a prevalent case-control study. Characteristics associated with female HIV infection were assessed using logistic regression modeling. At screening, HIV-infected women were more likely to have partners outside Lilongwe than HIV-uninfected women (24% versus 0%, p2 lifetime marriages (OR=9.0, CI=2.6-30.9) or >3 lifetime partners (OR=18.0, CI=3.1-103.6) and lower if either reported past couple HIV testing and counseling (OR=0.1, CI=0.04-0.3). Targeting women with migrating partners, promoting couple HIV testing and counseling, and limiting partners could slow HIV transmission