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IntroductionUptake of voluntary medical male circumcision (VMMC) remains a challenge in many settings. Innovative implementation strategies are required to scale-up VMMC uptake.MethodologyRITe was a multi-faceted intervention comprising transport reimbursement (R), intensified health education (IHE) and SMS/Telephone tracing (Te), which increased the uptake of VMMC among uncircumcised men with sexually transmitted infections (STIs) in Malawi. Using a concurrent exploratory mixed-method approach, we assessed the intervention's acceptability, feasibility and appropriateness among men with STIs and healthcare workers (HCWs) at Bwaila District Hospital. Participants completed Likert scale surveys and participated in-depth interviews (IDIs) and focus group discussions (FGDs). We calculated percentages of responses to survey items and summarized common themes using thematic analysis. Median scores and interquartile ranges (IQR) were calculated for acceptability, feasibility and appropriateness of each strategy at baseline and end-line and compared using the Wilcoxon signed rank test.ResultsA total of 300 surveys, 17 IDIs and 4 FGDs were conducted with men and HCWs between baseline and end-line. The mean age for men in the survey was 29 years (SD ±8) and most were married/cohabiting (59.3%). Mean age for HCWs was 38.5 years (SD ±7), and most were female (59.1%). For acceptability, participants agreed that RITe was welcome, approvable, and likable. Despite participants agreeing that RITe was a good idea, fit and suitability influenced appropriateness, particularly at baseline, which improved at end-line for Te and R. For feasibility, HCWs agreed that RITe was easy to implement, but expressed concerns that R (end-line median = 4, IQR: 2, 4) and Te (end-line median = 4, IQR: 4, 4), were unsustainable. Interviews corroborated the survey results. Participants reported that IHE provided important information, Te was a good reminder and R was attractive, but they reported barriers to R and Te such as electricity, limited access to phones and distrust in the government.ConclusionsThe RITe intervention was acceptable, feasible and appropriate. However, culture/religion and structural barriers affected perceptions of appropriateness and feasibility, respectively. Continued awareness raising on VMMC and addressing setting-specific structural factors are required to overcome barriers that impede demand-creation interventions for VMMC. more...

[This corrects the article DOI: 10.1371/journal.pone.0279619.].

Objective To evaluate the effect a multistrategy demand-creation and linkage intervention on voluntary medical male circumcision (VMMC) uptake, time to VMMC and predictors of VMMC uptake among men with sexually transmitted infections (STIs).Design Pragmatic preinterventional and postinterventional quasi-experimental study combined with a prospective observational design.Setting A public and specialised STI clinic in Lilongwe, Malawi.Population Uncircumcised men who presented to the STI clinic.Methods and intervention The intervention consisted of transport reimbursement (‘R’), intensified health education (‘I’) and short-messaging services/telephonic tracing (‘Te’), abbreviated (RITe). A preintervention phase was conducted at baseline while RITe was rolled-out in the intervention phase in a sequential manner called implementation blocks: ‘I’ only—block 1; ‘I+Te’—block 2 and RITe—block 3.Main outcome measures Primary: VMMC uptake and time to VMMC for the full intervention and for each block. Secondary: predictors of VMMC uptake.Results A total of 2230 uncircumcised men presented to the STI clinic. The mean age was 29 years (SD±9), 58% were married/cohabiting, HIV prevalence was 6.4% and 43% had urethral discharge. Compared with standard of care (8/514, 1.6%), uptake increased by 100% during the intervention period (55/1716, 3.2%) (p=0.048). ‘I’ (25/731, 113%, p=0.044) and RITe (17/477, 125%, p=0.044) significantly increased VMMC uptake. The median time to VMMC was shorter during the intervention period (6 days, IQR: 0, 13) compared with standard of care (15 days, IQR: 9, 18). There was no significant incremental effect on VMMC uptake and time to VMMC between blocks. Men with genital warts were 18 times more likely to receive VMMC (adjusted relative risk=18.74, 95% CI: 2.041 to 172.453).Conclusions Our intervention addressing barriers to VMMC improved VMMC uptake and time to VMMC among uncircumcised men with STIs, an important subpopulation for VMMC prioritisation.Trial registration number NCT04677374. more...

The SARS-CoV-2 pandemic led to the rapid transition of many research studies from in-person to telephone follow-up globally. For mental health research in low-income settings, tele-follow-up raises unique safety concerns due to the potential of identifying suicide risk in participants who cannot be immediately referred to in-person care. We developed and iteratively adapted a telephone-delivered protocol designed to follow a positive suicide risk assessment (SRA) screening. We describe the development and implementation of this SRA protocol during follow-up of a cohort of adults with depression in Malawi enrolled in the Sub-Saharan Africa Regional Partnership for Mental Health Capacity Building (SHARP) randomized control trial during the COVID-19 era. We assess protocol feasibility and performance, describe challenges and lessons learned during protocol development, and discuss how this protocol may function as a model for use in other settings. Transition from in-person to telephone SRAs was feasible and identified participants with suicidal ideation (SI). Follow-up protocol monitoring indicated a 100% resolution rate of SI in cases following the SRA during this period, indicating that this was an effective strategy for monitoring SI virtually. Over 2% of participants monitored by phone screened positive for SI in the first six months of protocol implementation. Most were passive risk (73%). There were no suicides or suicide attempts during the study period. Barriers to implementation included use of a contact person for participants without personal phones, intermittent network problems, and pre-paid phone plans delaying follow-up. Delays in follow-up due to challenges with reaching contact persons, intermittent network problems, and pre-paid phone plans should be considered in future adaptations. Future directions include validation studies for use of this protocol in its existing context. This protocol was successful at identifying suicide risk levels and providing research assistants and participants with structured follow-up and referral plans. The protocol can serve as a model for virtual SRA development and is currently being adapted for use in other contexts. more...

BackgroundPre-exposure prophylaxis (PrEP) reduces HIV acquisition risk by >90% and is a critical lever to reduce HIV incidence. Identifying individuals most likely to benefit from PrEP and retaining them on PrEP throughout HIV risk is critical to realize PrEP’s prevention potential. Individuals with sexually transmitted infections (STIs) are an obvious priority PrEP population, but there are no data from sub-Saharan Africa (SSA) confirming the effectiveness of integrating PrEP into STI clinics. Assisted partner notification may further enhance STI clinic–based PrEP programming by recruiting PrEP users from the pool of named sexual partners of individuals presenting with an incident STI. However, the acceptability, feasibility, and effectiveness of these integrated and enhanced strategies are unknown. ObjectiveThis study aims to describe the implementation outcomes of acceptability, feasibility, and effectiveness (regarding PrEP uptake and persistence) of integrating an enhanced PrEP implementation strategy into an STI clinic in Malawi. MethodsThe enhanced PrEP STI study is a prospective cohort study enrolling patients who are eligible for PrEP (aged ≥15 years) who are seeking STI services at a Lilongwe-based STI clinic. Data collection relies on a combination of in-depth interviews, patient and clinic staff surveys, and clinic record review. All enrolled PrEP users will be screened for acute HIV infection and receive quarterly testing for Neisseria gonorrhea, Chlamydia trachomatis, and syphilis. Participants will be asked to name recent sexual partners for assisted notification; returning partners will be screened for PrEP eligibility and, if interested, enrolled into the cohort of PrEP initiators. We will also enroll patients who are eligible for PrEP but choose not to initiate it, from the STI clinic. Patient participants will be followed for 6 months; we will assess self-reported PrEP use, PrEP refills, sexual behaviors, perceived HIV risk, and incident STIs. Clinic staff participants will be interviewed at baseline and at approximately 6 months and will complete surveys examining the perceived acceptability and feasibility of the integrated and enhanced PrEP strategy. ResultsEnrollment began in March 2022 and is projected to continue until February 2023, with patient participant follow-up through August 2023. The results of this study are expected to be reported in 2024. ConclusionsThis study will generate important evidence regarding the potential integration of PrEP services into STI clinics in SSA and preliminary data regarding the effectiveness of an enhanced intervention that includes assisted partner notification as a strategy to identify potential PrEP users. Furthermore, this trial will provide some of the first insights into STI incidence among PrEP users recruited from an STI clinic in SSA—critical data to inform the use of etiologic STI testing where syndromic management is the current standard. These findings will help to design future PrEP implementation strategies in SSA. Trial RegistrationClinicalTrials.gov NCT05307991; https://clinicaltrials.gov/ct2/show/NCT05307991 International Registered Report Identifier (IRRID)DERR1-10.2196/37395 more...

Summary: Background: The identification of baseline host determinants that associate with robust HIV-1 vaccine-induced immune responses could aid HIV-1 vaccine development. We aimed to assess both the collective and relative performance of baseline characteristics in classifying individual participants in nine different Phase 1-2 HIV-1 vaccine clinical trials (26 vaccine regimens, conducted in Africa and in the Americas) as High HIV-1 vaccine responders. Methods: This was a meta-analysis of individual participant data, with studies chosen based on participant-level (vs. study-level summary) data availability within the HIV-1 Vaccine Trials Network. We assessed the performance of 25 baseline characteristics (demographics, safety haematological measurements, vital signs, assay background measurements) and estimated the relative importance of each characteristic in classifying 831 participants as High (defined as within the top 25th percentile among positive responders or above the assay upper limit of quantification) versus Non-High responders. Immune response outcomes included HIV-1-specific serum IgG binding antibodies and Env-specific CD4+ T-cell responses assessed two weeks post-last dose, all measured at central HVTN laboratories. Three variable importance approaches based on SuperLearner ensemble machine learning were considered. Findings: Overall, 30.1%, 50.5%, 36.2%, and 13.9% of participants were categorized as High responders for gp120 IgG, gp140 IgG, gp41 IgG, and Env-specific CD4+ T-cell vaccine-induced responses, respectively. When including all baseline characteristics, moderate performance was achieved for the classification of High responder status for the binding antibody responses, with cross-validated areas under the ROC curve (CV-AUC) of 0.72 (95% CI: 0.68, 0.76) for gp120 IgG, 0.73 (0.69, 0.76) for gp140 IgG, and 0.67 (95% CI: 0.63, 0.72) for gp41 IgG. In contrast, the collection of all baseline characteristics yielded little improvement over chance for predicting High Env-specific CD4+ T-cell responses [CV-AUC: 0.53 (0.48, 0.58)]. While estimated variable importance patterns differed across the three approaches, female sex assigned at birth, lower height, and higher total white blood cell count emerged as significant predictors of High responder status across multiple immune response outcomes using Approach 1. Of these three baseline variables, total white blood cell count ranked highly across all three approaches for predicting vaccine-induced gp41 and gp140 High responder status. Interpretation: The identified features should be studied further in pursuit of intervention strategies to improve vaccine responses and may be adjusted for in analyses of immune response data to enhance statistical power. Funding: National Institute of Allergy and Infectious Diseases (UM1AI068635 to YH, UM1AI068614 to GDT, UM1AI068618 to MJM, and UM1 AI069511 to MCK), the Duke CFAR P30 AI064518 to GDT, and National Institute of Dental and Craniofacial Research (R01DE027245 to JJK). This work was also supported by the Bill and Melinda Gates Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding sources. more...

Background Viral load (VL) testing coverage remains low particularly in resource limited countries despite recommendation by World Health Organization, and Malawi is no exception. A quality improvement (QI) approach was used to improve VL testing coverage from 27% to a target of 80% at an urban health facility in Malawi. Methods A QI study employing a time-series quasi-experimental design with no comparison group was conducted at Chilomoni health centre in Blantyre from April 2020 to July 2020. A retrospective record review of all patient records (257) from 8 weeks before the study was conducted to determine baseline VL testing coverage. Root cause analysis of low VL testing coverage was done using fish-bone tool and factors prioritized using a Pareto-chart. Priority factors included inadequate capacity to update electronic medical records and competing tasks. Change ideas were identified and prioritized using an effort-impact matrix. Two change ideas; re-orienting ART providers on VL test order in EMR and dedicated ART provider to serve VL tested patients were implemented and tested in 5 Plan-Do-Study-Act (PDSA) cycles from the Model for Improvement (MFI), each lasting one week. The latter was tested, and adapted in 3 cycles, and eventually adopted for monitoring for another 5 weeks. VL testing coverage was tracked throughout the study using run charts and p-charts. Results VL testing coverage increased from 27% to 71% by the end of the study, with children aged 0 to 14 years having the lowest coverage throughout the study. Conclusion The MFI as a QI approach improved VL testing coverage through implementation of contextualized change ideas. A reliable data system, leadership buy-in and commitment are important for sustained improvement. Future research should focus on evaluating sustainability of improved VL testing coverage at the health facility and assessing barriers to VL testing among the paediatric population. more...

Background Couples HIV Counselling and Testing (CHCT) has been found to be potentially beneficial than individual HIV Counselling and Testing for prevention and treatment of HIV. However, there are few health care opportunities for men and women to access health services together, leading to underutilization of CHCT service. Integrating female Sexual and Reproductive Health (SRH) services into male-dominated service could be more effective than trying to integrate men’s health services into female-dominated health services. A potential site for male-female service integration could be Voluntary Medical Male Circumcision (VMMC) centers. Methodology We conducted a qualitative study in Lilongwe, Malawi between June to August 2018. Twenty VMMC clients, 20 peers and 20 VMMC providers completed individual in-depth interviews to share their opinions on what they thought about integrating CHCT and other SRH Services into VMMC services. These proposed SRH services include family planning, cervical cancer screening, sexually transmitted infection management and pre-exposure prophylaxis (PrEP). Content analysis was used to analyze the results. Results All participants were receptive to integration of CHCT, and most accepted the integration of SRH services into VMMC Services. Most VMMC clients, peers and care providers said that CHCT integration would help couples to know their HIV status, prevent HIV transmission, encourage healthy relationships, and provide a chance for women to participate in VMMC counselling and wound care. However, integration of other services, such as family planning and cervical cancer screening, drew mixed opinions among participants. Most VMMC clients, peers and providers felt that integration of services would promote male involvement and increase men’s knowledge in feminine sexual reproductive health services. A few providers expressed concerns over service integration, citing reasons such as overcrowding, work overload, gender mixing, and lack of provider capacity and space. Most participants supported integrating PrEP with VMMC Services and felt that PrEP would complement VMMC in HIV prevention. Few providers, peers and VMMC clients felt the addition of PrEP to VMMC services would lead to high-risk sexual activity that would then increase the risk for HIV acquisition. A few participants recommended community sensitization when integrating some of sexual reproductive health services into VMMC Services to mitigate negative perceptions about VMMC services and encourage service uptake among couples Conclusion Most participants service providers, VMMC clients and Peers were receptive to integrating SRH services, particularly HIV prevention services such as CHCT and PrEP, into male dominated VMMC services. Adequate community sensitization is required when introducing other SRH services into VMMC services. more...

Introduction Long-term care engagement of women on antiretroviral therapy (ART) is essential to effective HIV public health measures. We sought to explore factors associated with a history of HIV treatment interruption among pregnant women living with HIV presenting to an antenatal clinic in Lilongwe, Malawi. Methods We performed a cross-sectional study of pregnant women living with HIV who had a history of ART interruption presenting for antenatal care. Women were categorized as either retained in HIV treatment or reinitiating care after loss-to-follow up (LTFU). To understand factors associated with treatment interruption, we surveyed socio-demographic and partner relationship characteristics. Crude and adjusted prevalence ratios (aPR) for factors associated with ART interruption were estimated using modified Poisson regression with robust variance. We additionally present patients’ reasons for ART interruption. Results We enrolled 541 pregnant women living with HIV (391 retained and 150 reinitiating). The median age was 30 years (interquartile range (IQR): 25–34). Factors associated with a history of LTFU were age Conclusions Interventions that simplify the ART clinic transfer process, facilitate partner disclosure, and provide counseling about the importance of lifelong ART beyond pregnancy and breastfeeding should be further evaluated for improving retention in ART treatment of women living with HIV in Malawi. more...

Introduction Voluntary medical male circumcision (VMMC) is one of the key interventions for HIV prevention. However, its uptake among men in Malawi is low. Implementation science strategies for demand creation of VMMC increase uptake. We designed an implementation science demand-creation intervention to increase the uptake of VMMC among men with sexually transmitted infections (STIs).Methods and analysis We designed a pragmatic pre-interventional and post-interventional quasi-experimental study combined with a prospective observational design to determine the uptake, acceptability, appropriateness and feasibility of a multifaceted intervention for scale up of uptake of VMMC among men with STIs at Bwaila STI clinic in Lilongwe, Malawi. The intervention includes transport reimbursement (R), intensified health education (I) and short messaging service (SMS)/telephonic tracing (Te) (RITe). The intervention will be implemented in phases: pre-implementation and implementation. Pre-implementation phase will be used for collecting baseline data, while the RITe intervention will be rolled-out in the implementation phase. The RITe intervention will be implemented in a sequential and incremental manner called implementation blocks: block 1: intensified health education; block 2: intensified health education and SMS/telephonic tracing; and block 3: intensified health education, SMS/telephonic tracing and transport reimbursement. The target sample size is 80 uncircumcised men for each intervention block, including the pre-implementation sample, making a total of 320 men (280 total, 70 per block will be surveyed). The primary outcome is uptake of VMMC during the implementation period. Mixed methods assessments will be conducted to evaluate the acceptability, appropriateness and feasibility of the RITe intervention.Ethics and dissemination The study protocol was approved by the Malawi’s National Health Sciences Research Ethics Committee (approval number: 19/10/2412), University of North Carolina at Chapel Hill’s Institutional Review Board (approval number: 19–2559) and University of the Witwatersrand’s Health Research Ethics Committee (approval number: M200328). Results will be disseminated via publication in a peer-reviewed journal and presentations at relevant scientific conferences and meetings.Trial registration number NCT04677374. more...

BackgroundPneumonia is a leading cause of mortality in children MethodsParticipants were 1-59 months old with World Health Organization-defined severe pneumonia and hypoxemia, severe malnutrition, and/or HIV exposure/infection. All participants received intravenous antibiotics per standard care. First-line antibiotics were benzylpenicillin and gentamicin for five days. Study staff assessed patients for first-line antibiotic failure daily between days 3-6. When identified, patients failing antibiotics were switched to second-line ceftriaxone. Analyses excluded children receiving ceftriaxone and/or deceased by hospital day two. We compared characteristics between patients with and without treatment failure and fit multivariable logistic regression models to evaluate associations between treatment failure and admission characteristics.ResultsFrom June 2015-March 2018, 644 children were enrolled and 538 analyzed. Antibiotic failure was identified in 251 (46.7%) participants, and 19/251 (7.6%) died. Treatment failure occurred more frequently with severe malnutrition (50.2% (126/251) vs 28.2% (81/287), pConclusionSevere malnutrition and pre-hospital antibiotic use predicted antibiotic treatment failure in this high-risk severe pneumonia pediatric population in Malawi. Our findings suggest addressing complex sociomedical conditions like severe malnutrition and improving pneumonia etiology diagnostics will be key for better targeting interventions to improve childhood pneumonia outcomes. more...

Depressive disorders are a leading cause of global morbidity and remain disproportionately high in low- and middle-income settings. Stressful life events (SLEs) are known risk factors for depressive episodes and worsened depressive severity, yet are under-researched in comparison to other depression risk factors. As depression is often comorbid with hypertension, diabetes, and other noncommunicable diseases (NCDs), research into this relationship among patients with NCDs is particularly relevant to increasing opportunities for integrated depression and NCD care. This study aims to estimate the cross-sectional association between SLEs in the three months preceding baseline interviews and baseline depressive severity among patients with at least mild depressive symptoms who are seeking NCD care at 10 NCD clinics across Malawi. SLEs were measured by the Life Events Survey and depressive severity (mild vs. moderate to severe) was measured by the Patient Health Questionnaire-9. The study population (n = 708) was predominately currently employed, grand multiparous (5-8 children) women with a primary education level. Two thirds (63%) had mild depression while 26%, 8%, and 3% had moderate, moderately severe, and severe depression, respectively. Nearly all participants (94%) reported at least one recent SLE, with the most common reported SLEs being financial stress (48%), relationship changes (45%), death of a family member or friend (41%), or serious illness of a family member or friend (39%). Divorce/separation, estrangement from a family member, losing source of income, and major new health problems were significant predictors of greater (moderate or severe) depressive severity compared to mild severity. Having a major new health problem or experiencing divorce/separation resulted in particularly high risk of more severe depression. After adjustment, each additional SLE was associated with a 9% increased risk of moderate or worse depressive severity compared to mild depressive severity (RR: 1.09; (95% CI: 1.05, 1.13), p more...

BackgroundIn 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 findingsWe 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.ConclusionsIn 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. more...

BackgroundDNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with harmonized trial designs. HIV Vaccine Trials Network (HVTN) 111 tested DNA plasmid prime by needle or needleless injection device (Biojector) and DNA plasmid plus gp120 protein plus MF59 adjuvant boost. HVTN 100 tested ALVAC prime and ALVAC plus gp120 protein plus MF59 adjuvant boost (same protein/adjuvant as HVTN 111) by needle.Methods and findingsThe primary endpoints for this analysis were binding antibody (bAb) responses to HIV antigens (gp120 from strains ZM96, 1086, and TV1; variable 1 and 2 [V1V2] regions of gp120 from strains TV1, 1086, and B.CaseA, as 1086 V1V2 and B.CaseA were correlates of risk in the RV144 efficacy trial), neutralizing antibody (nAb) responses to pseudoviruses TV1c8.2 and MW925.26, and cellular responses to vaccine-matched antigens (envelope [Env] from strains ZM96, 1086, and TV1; and Gag from strains LAI and ZM96) at month 6.5, two weeks after the fourth vaccination. Per-protocol cohorts included vaccine recipients from HVTN 100 (n = 186, 60% male, median age 23 years) enrolled between February 9, 2015, and May 26, 2015 and from HVTN 111 (n = 56, 48% male, median age 24 years) enrolled between June 21, 2016, and July 13, 2017. IgG bAb response rates were 100% to 3 Env gp120 antigens in both trials. Response rates to V1V2 were lower and similar in both trials except to vaccine-matched 1086 V1V2, with rates significantly higher for the DNA-primed regimen than the ALVAC-primed regimen: 96.6% versus 72.7% (difference = 23.9%, 95% CI 15.6%-32.2%, p < 0.001). Among positive responders, bAb net mean fluorescence intensity (MFI) was significantly higher with the DNA-primed regimen than ALVAC-primed for 1086 V1V2 (geometric mean [GM] 2,833.3 versus 1,200.9; ratio = 2.36, 95% CI 1.42-3.92, p < 0.001) and B.CaseA V1V2 (GM 2314.0 versus 744.6, ratio = 3.11, 95% CI 1.51-6.38, p = 0.002). nAb response rates were >98% in both trials, with significantly higher 50% inhibitory dilution (ID50) among DNA-primed positive responders (n = 53) versus ALVAC-primed (n = 182) to tier 1A MW965.26 (GM 577.7 versus 265.7, ratio = 2.17, 95% CI 1.67-2.83, p < 0.001) and to TV1c8.2 (GM 187.3 versus 100.4, ratio = 1.87, 95% CI 1.48-2.35, p < 0.001). CD4+ T-cell response rates were significantly higher with DNA plasmid prime via Biojector than ALVAC prime (91.4% versus 52.8%, difference = 38.6%, 95% CI 20.5%-56.6%, p < 0.001 for ZM96.C; 88.0% versus 43.1%, difference = 44.9%, 95% CI 26.7%-63.1%, p < 0.001 for 1086.C; 55.5% versus 2.2%, difference = 53.3%, 95% CI 23.9%-82.7%, p < 0.001 for Gag LAI/ZM96). The study's main limitations include the nonrandomized comparison of vaccines from 2 different trials, the lack of data on immune responses to other non-vaccine-matched antigens, and the uncertain clinical significance of the observed immunological effects.ConclusionsIn this study, we found that further investigation of DNA/protein regimens is warranted given enhanced immunogenicity to the V1V2 correlates of decreased HIV-1 acquisition risk identified in RV144, the only HIV vaccine trial to date to show any efficacy. more...

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. more...

Since emergency approval of COVID-19 vaccines for children aged between 12 and 15 years old was recently obtained in the United States and Europe, we aimed to assess the willingness to vaccinate children with a COVID-19 vaccine in lower- and middle-income countries (LMICs). Therefore, we launched an online cross-sectional survey in several LMICs. Questions relating to socio-demographic information, knowledge of COVID-19, level of fear/worry of being infected with COVID-19, and willingness to vaccinate children with the COVID-19 vaccine at 50%, 75% and 95% effectiveness levels, were asked. Of the 6571 participants (mean age = 39 ± 14 years), 64.0%, 72.6%, and 92.9% were willing to vaccinate children at 50%, 75%, and 95% effectiveness levels, respectively. Respondents who were undergraduates, who were more worried/fearful about COVID-19, had higher knowledge scores regarding COVID-19, and a higher belief that COVID-19 vaccination is important to protect others, were more willing to accept COVID-19 vaccination of children. COVID-19 vaccination of children will limit the spread of the virus, especially in schools; it may decrease the need for school closures which has a negative effect on child development. Findings from this study are useful for health promotion strategies during COVID-19 vaccination implementation among children in LMICs. more...

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. more...

BackgroundOral Pre-Exposure Prophylaxis (PrEP) is an effective HIV prevention strategy for adherent users. Adolescent girls and young women (AGYW) in sub-Saharan Africa may particularly benefit from PrEP because of the disproportionate burden of HIV in this group. Understanding potential users' perceptions of and interest in using PrEP is critical to promote the utilization of PrEP by individuals at risk of HIV.MethodsThis qualitative investigation of AGYW's knowledge of and interest in PrEP use was conducted in the context of Girl Power, a quasi-experimental cohort study comparing four models of service delivery at four health centers in Lilongwe, Malawi. We conducted individual in-depth interviews (IDIs) with 40 HIV-negative AGYW ages 15-24 years old six months after enrolment in the parent study. An explanation of PrEP was provided to participants. Interview topics included participants' prior knowledge of, interest in, concerns about, and delivery preferences for PrEP. Analysis consisted of structural coding of interview transcripts corresponding to interview topics, summary of responses within these topics, and identification and description of emerging themes within each topic.ResultsNone of the AGYW had knowledge of PrEP prior to the IDIs, but once explained, a majority expressed an interest in using it due to inconsistencies in condom use, condom use errors, their own or their partners' concurrent sexual partnerships, and rape. Most AGYW hoped that PrEP would be available in youth-friendly sections of health centers for easy access and youth-friendly counselling. They suggested that discrete packaging of PrEP would be needed to ensure user privacy. Concerns about relationship destabilization and accusations of promiscuity were raised as potential barriers to use.ConclusionGeneral interest in PrEP among AGYW was high. Discrete packaging and access to youth-friendly PrEP delivery modalities may facilitate the utilization of PrEP as a prevention strategy among sexually active AGYW. Attention to potential negative reactions from partners and community members to PrEP use will be needed when introducing PrEP to this population. more...

BackgroundPerinatal depression (PND) can interfere with HIV care engagement and outcomes. We examined experiences of PND among women living with HIV (WLWH) in Malawi.MethodsWe screened 73 WLWH presenting for perinatal care in Lilongwe, Malawi using the Edinburgh Postnatal Depression Scale (EPDS). We conducted qualitative interviews with 24 women experiencing PND and analyzed data using inductive and deductive coding and narrative analysis.ResultsWomen experienced a double burden of physical and mental illness, expressed as pain in one's heart. Receiving an HIV diagnosis unexpectedly during antenatal care was a key contributor to developing PND. This development was influenced by stigmatization and social support.ConclusionsThese findings highlight the need to recognize the mental health implications of routine screening for HIV and to routinely screen and treat PND among WLWH. Culturally appropriate mental health interventions are needed in settings with a high HIV burden. more...

Objective This review was conducted to identify interventions effective in improving uptake and retention of HIV-positive mothers and their infants in prevention of mother to child transmission (PMTCT) services in low-income and middle-income countries (LMICs) in order to inform programme planning.Methods We conducted a systematic review of studies comparing usual care with any intervention to improve uptake and retention of HIV-positive pregnant or breastfeeding women and their children from birth to 2 years of age in PMTCT services in LMICs. Twenty-two electronic databases were searched from inception to 15 January 2018, for randomised, quasi-randomised and non-randomised controlled trials, and interrupted time series studies; reference lists of included articles were searched for relevant articles. Risk of bias was assessed using the Cochrane Effective Practice and Organisation of Care group criteria. Random-effects meta-analysis was conducted for studies reporting similar interventions and outcomes.Results We identified 29 837 articles, of which 18 studies were included in our review. Because of heterogeneity in interventions and outcome measures, only one meta-analysis of two studies and one outcome was conducted; we found a statistically significant increase in antiretroviral therapy (ART) use during pregnancy for integration of HIV and antenatal care relative to standard non-integrated care (pooled AOR=2.69; 95% CI 1.25 to 5.78, p=0.0113). The remaining studies assessing other patient, provider or health system interventions were synthesised narratively, with small effects seen across intervention categories for both maternal and infant PMTCT outcomes based predominately on evidence with moderate to high risk of bias.Conclusions Evidence on the effectiveness of interventions to improve uptake and retention of mothers and infants in PMTCT care is lacking. Our findings suggest that integration of HIV and antenatal care may improve ART use during pregnancy. Future studies to replicate promising approaches are needed. Improved reporting of key methodological criteria will facilitate interpretation of findings and improve the utility of evidence to PMTCT programme planners.PROSPERO registration number CRD42015020829. more...

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 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. more...

BACKGROUND:Cabotegravir (CAB) is a novel strand-transfer integrase inhibitor being developed for HIV treatment and prevention. CAB is formulated both as an immediate-release oral tablet for daily administration and as a long-acting injectable suspension (long-acting CAB [CAB LA]) for intramuscular (IM) administration, which delivers prolonged plasma exposure to the drug after IM injection. HIV Prevention Trials Network study 077 (HPTN 077) evaluated the safety, tolerability, and pharmacokinetics of CAB LA in HIV-uninfected males and females at 8 sites in Brazil, Malawi, South Africa, and the United States. METHODS AND FINDINGS:HPTN 077 was a double-blind, placebo-controlled phase 2a trial. Healthy individuals age 18-65 years at low HIV risk were randomized (3:1) to receive CAB or placebo (PBO). In the initial oral phase, participants received 1 daily oral tablet (CAB or PBO) for 4 weeks. Those without safety concerns in the oral phase continued and received injections in the injection phase (Cohort 1: 3 injections of CAB LA 800 mg or 0.9% saline as PBO IM every 12 weeks for 3 injection cycles; Cohort 2: CAB LA 600 mg or PBO IM for 5 injection cycles; the first 2 injections in Cohort 2 were separated by 4 weeks, the rest by 8 weeks). The primary analysis included weeks 5 to 41 of study participation, encompassing the injection phase. The cohorts were enrolled sequentially. Primary outcomes were safety and tolerability. Secondary outcomes included pharmacokinetics and events occurring during the oral and injection phases. Between February 9, 2015, and May 27, 2016, the study screened 443 individuals and enrolled 110 participants in Cohort 1 and 89 eligible participants in Cohort 2. Participant population characteristics were as follows: 66% female at birth; median age 31 years; 27% non-Hispanic white, 41% non-Hispanic black, 24% Hispanic/Latino, 3% Asian, and 6% mixed/other; and 6 transgender men and 1 transgender woman. Twenty-two (11%) participants discontinued the oral study product; 6 of these were for clinical or laboratory adverse events (AEs). Of those who received at least 1 CAB LA injection, 80% of Cohort 1 and 92% of Cohort 2 participants completed all injections; injection course completion rates were not different from those in the PBO arm. Injection site reactions (ISRs) were common (92% of Cohort 1 and 88% of Cohort 2 participants who received CAB LA reported any ISR). ISRs were mostly Grade 1 (mild) to Grade 2 (moderate), and 1 ISR event (Cohort 1) led to product discontinuation. Grade 2 or higher ISRs were the only AEs reported more commonly among CAB LA recipients than PBO recipients. Two Grade 3 (severe) ISRs occurred in CAB recipients, 1 in each cohort, but did not lead to product discontinuation in either case. Seven incident sexually transmitted infections were diagnosed in 6 participants. One HIV infection occurred in a participant 48 weeks after last injection of CAB LA: CAB was not detectable in plasma both at the time of first reactive HIV test and at the study visit 12 weeks prior to the first reactive test. Participants in Cohort 2 (unlike Cohort 1) consistently met prespecified pharmacokinetic targets of at least 95% of participants maintaining CAB trough concentrations above PA-IC90, and 80% maintaining trough concentrations above 4× PA-IC90. Study limitations include a modest sample size, a short course of injections, and a low-risk study population. CONCLUSIONS:In this study, CAB LA was well tolerated at the doses and dosing intervals used. ISRs were common, but infrequently led to product discontinuation. CAB LA 600 mg every 8 weeks met pharmacokinetic targets for both male and female study participants. The safety and pharmacokinetic results observed support the further development of CAB LA, and efficacy studies of CAB LA for HIV treatment and prevention are in progress. TRIAL REGISTRATION:ClinicalTrials.gov Registry: ClinicalTrials.gov Trial number: NCT02178800. more...

BackgroundEffective antiretroviral therapy during pregnancy minimizes the risk of vertical HIV transmission. Some women present late in their pregnancy for first antenatal visit; whether these women achieve viral suppression by delivery and how suppression varies with time on ART is unclear.MethodsWe conducted a prospective cohort study of HIV-infected pregnant women initiating antiretroviral therapy for the first time at Bwaila Hospital in Lilongwe, Malawi from June 2015 to November 2016. Multivariable Poisson models with robust variance estimators were used to estimate risk ratios (RR) and 95% confidence intervals (CI) of the association between duration of ART and both viral load (VL) ≥1000 copies/ml and VL ≥40 copies/ml at delivery.ResultsOf the 252 women who had viral load testing at delivery, 40 (16%) and 78 (31%) had VL ≥1000 copies/ml and VL ≥40 copies/ml, respectively. The proportion of women with poor adherence to ART was higher among women who were on ART for ≤12 weeks (9/50 = 18.0%) than among those who were on ART for 13-35 weeks (18/194 = 9.3%). Compared to women who were on ART for ≤12 weeks, women who were on ART for 13-20 weeks (RR = 0.52; 95% CI: 0.36-0.74) or 21-35 weeks (RR = 0.26; 95% CI: 0.14-0.48) had a lower risk of VL ≥40 copies/ml at delivery. Similar comparisons for VL ≥1000 copies/ml at delivery showed decrease in risk although not significant for those on ART 13-20 weeks.ConclusionLonger duration of ART during pregnancy was associated with suppressed viral load at delivery. Early ANC attendance in pregnancy to facilitate prompt ART initiation for HIV-positive women is essential in the effort to eliminate HIV vertical transmission. more...

BACKGROUND:In the era of increased access to HIV testing and antiretroviral treatment (ART), the impact of HIV and ART status on inpatient mortality in Malawi is unknown. METHODS:We prospectively followed adult inpatients at Kamuzu Central Hospital medical wards in Lilongwe, Malawi, between 2011 and 2012, to evaluate causes of mortality, and the impact of HIV and ART status on mortality. We divided the study population into five categories: HIV-negative, new HIV-positive, ART-naïve patients, new ART-initiators, and ART-experienced. We used multivariate binomial regression models to compare risk of death between categories. RESULTS:Among 2911 admitted patients the mean age was 38.5 years, and 50% were women. Eighty-one percent (81%) of patients had a known HIV status at the time of discharge or death. Mortality was 19.4% and varied between 13.9% (HIV-negative patients) and 32.9% (HIV-positive patients on ART ≤1 year). In multivariable analyses adjusted for age, sex and leading causes of mortality, being new HIV-positive (RR = 1.64 95% CI: 1.16-2.32), ART-naive (RR = 2.28 95% CI: 1.66-2.32) or being a new ART-initiator (RR = 2.41 95% CI: 1.85-3.14) were associated with elevated risk of mortality compared to HIV-negative patients. ART-experienced patients had comparable mortality (RR = 1.33 95% CI: 0.94-1.88) to HIV-negative patients. CONCLUSION:HIV related mortality remains high among medical inpatients, especially among HIV-positive patients who recently initiated ART or have not started ART yet. more...

As access to antiretroviral therapy increases, more HIV-infected patients in sub-Saharan Africa may desire fertility. We conducted a cross-sectional study of reproductive health knowledge, attitudes and practices to identify factors associated with desired fertility among women and men receiving care at two large public HIV clinics in Lilongwe, Malawi. Research assistants administered questionnaires to participants. We performed descriptive, bivariable and multivariable analysis of factors related to desired fertility and of factors related to contraceptive non-use among participants who did not desire fertility. One-third of participants desired future children. Having a partner who desired fertility and having lower parity were associated with desiring children among both genders. For women, believing that pregnancy was unhealthy was associated with decreased fertility desire. Fifty-five percent of women and 69% of men who did not want children in the future reported using contraception at last intercourse. Increasing age, lower parity, and making the decision to use contraception herself were associated with contraceptive non-use among women who did not desire fertility. Having discussed family planning with his partner was associated with contraceptive use among men who did not desire fertility. Knowledge of these factors can guide reproductive health counseling and service provision. more...

BACKGROUND:In Malawi's PMTCT Option B+ program, HIV-infected pregnant women who are already receiving ART are continued on their current therapy regimen without testing for treatment failure at the first antenatal care (ANC) visit. HIV RNA screening at ANC may identify women with treatment failure and ensure that viral suppression is maintained throughout the pregnancy. METHODS:We conducted a cross-sectional study of HIV-infected pregnant women who had been receiving ART for at least 6 months at the first ANC visit under the PMTCT Option B+ program at Bwaila Hospital in Lilongwe, Malawi from June 2015 to December 2017. Poisson regression models with robust variance were used to investigate the predictors of ART treatment failure defined as viral load ≥1000 copies/ml. RESULTS:The median age of 864 women tested for ART failure was 31.1 years (interquartile range: 26.9-34.5). The prevalence of treatment failure was 7.6% (95% confidence interval (CI): 6.0-9.6). CD4 cell count (adjusted prevalence ratio (aPR) = 0.57; 95% CI: 0.50-0.65) was strongly associated with treatment failure. CONCLUSION:The low prevalence of treatment failure among women presenting for their first ANC in urban Malawi demonstrates success of Option B+ in maintaining viral suppression and suggests progress towards the last 90% of the UNAIDS 90-90-90 targets. Women failing on ART should be identified early for adherence counseling and may require switching to an alternative ART regimen. more...

BackgroundFine needle aspiration cytology (FNAC) has been widely accepted to be a safe, accurate, prompt and inexpensive procedure for diagnosis of both neoplastic and infectious diseases in adult and pediatric populations. Despite its value for diagnosis, FNAC is underutilized in resource limited countries. We reviewed the utilization of FNAC after it was introduced at Kamuzu Central Hospital (KCH).MethodsA retrospective review of all FNAC performed at KCH laboratory during the period of January 2012 to July 2014 was conducted using an electronic database from KCH laboratory. We evaluated factors associated with a diagnostic sample using multivariate logistic regression model.Results750 FNAC were reviewed from 722 patients: 56.9% were adults >15 years and 54% were female. The number of FNAC increased annually from 56 (2012) to 379 (2013) to 315 (up to July 2014). Of 750 FNAC, 56.4% were performed by non-pathologists. The most common sites were lymph nodes (38.1%), abdomen (25.8%), breast (16.3%), and head & neck (15.7%). Most of the samples (77.6%) were diagnostic. FNAC was more likely to be diagnostic if performed by pathologists versus non-pathologists (OR 1.78, 95% CI 1.20-2.64), in 2013 compared to 2012 (OR 1.95, 95% CI 1.05-3.56), or performed on a deep lesion versus a subcutaneous lesion (OR 1.71, 95% CI 1.15-2.5), or if samples were taken from the head and neck (OR 2.4, 95% CI: 1.39-4.39), and abdomen (OR 2.66, 95%CI1.59-4.42) compared to those from the lymph nodes. The odds of a diagnostic test did not differ significantly according to gender, HIV status, or age groups.ConclusionMost FNACs successfully diagnosed the presence or absence of disease, with substantial improvements over time. However, training for non-pathologists may facilitate more diagnostic results. more...

Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection. more...

To ensure the health of mothers and children, prevention of mother-to-child HIV transmission (PMTCT) programs test women for HIV, engage HIV-positive women in care, and promote recommended breastfeeding practices. Under Malawi's Option B+ PMTCT program, ~20% of women are lost-to-follow-up (LTFU) and little is known about their breastfeeding practices. The purpose of this study is to describe facilitators and barriers to Option B+ participation and how participation influences breastfeeding duration. We conducted in-depth interviews with HIV-positive women in Option B+ (n = 32) or LTFU from Option B+ (n = 32). They were recruited from four government clinics in Lilongwe District and had a child aged 0-23 months. Women in Option B+ had better disclosure experiences and more social support than LTFU women. The most common reasons for LTFU were fear of HIV disclosure, anticipated or experienced stigma, and insufficient social support. Other reasons included: non-acceptance of HIV status, antiretroviral therapy (ART) side effects, lack of funds for transport, and negative experiences with clinic staff. Worries about possible transmission, even while on ART, influenced timing of weaning for some women in Option B+. Despite their knowledge of the risk of HIV transmission to the child, most LTFU women continued to breastfeed after stopping ART because they considered breastmilk to be an important source of nutrients for the child. Given that HIV-positive Malawian women LTFU from Option B+ breastfeed in the absence of ART, efforts are needed to use evidence-based strategies to address the barriers to Option B+ participation and avert preventable transmission through breastmilk. more...

Human immunodeficiency virus (HIV) contributes to nearly 20% of all deaths in children under five years of age in Malawi. Expanded coverage of antiretroviral therapy has allowed children to access treatment on an outpatient basis. Little is known about characteristics of the final outpatient encounter prior to mortality in the outpatient setting.This retrospective cohort study assessed clinical factors associated with mortality among HIV-exposed infants and HIV-infected children less than 18 years of age at the Baylor College of Medicine Abbott Fund Children's Center of Excellence in Lilongwe, Malawi. We compared clinical indicators documented from the final outpatient encounter for patients who died in the outpatient setting versus those who were alive after their penultimate clinical encounter.Of the 8,546 patients who were attended to over a 10-year period at the Baylor Center of Excellence, 851 had died (10%). Of children who died, 392 (46%) were directly admitted to the hospital after their last clinical encounter and died as inpatients. Of the remaining 459 who died as outpatients after their last visit, 53.5% had a World Health Organization (WHO) stage IV condition at their last visit, and 25% had a WHO stage III condition. Multivariate regression analysis demonstrated that poor nutritional status, female gender, shorter time as a patient, more clinical encounters in the prior month, if last visit was an unscheduled sick visit, and if the patient had lost weight since their prior visit independently predicted increased mortality in the outpatient setting after the final clinical encounter.Clinical indicators may assist in identifying children with HIV who have increased risk of mortality in the outpatient setting. Recognizing these indicators may aid in identifying HIV-infected children who require a higher level of care or closer follow-up. more...

Women who report use of postpartum family planning may not continue their initial method or use it consistently. Understanding the patterns of method uptake, discontinuation, and switching among women after delivery is important to promote uptake and continuation of effective methods of contraception. This is a secondary analysis of 634 Malawian women enrolled into a prospective cohort study after delivery. They completed baseline surveys upon enrollment and follow-up telephone surveys 3, 6, and 12 months post-delivery. Women were included in this analysis if they had completed at least the 3- and 6-month post-delivery surveys. Descriptive statistics were used to assess contraceptive method mix and patterns of switching, whereas Pearson's χ2 tests were used for bivariable analyses to compare characteristics of women who continued and discontinued their initial post-delivery contraceptive method. Among the 479 women included in this analysis, the use of abstinence/traditional methods decreased and the use of long-acting and permanent methods (LAPM) increased over time. Almost half (47%) discontinued the contraceptive method reported at 3-months post-delivery; women using injectables or LAPM at 3-months post-delivery were significantly more likely to continue their method than those using non-modern methods (p more...

The HIV care continuum among female sex workers (FSW), a key population, has not been well characterized, especially within the generalized epidemics of sub-Saharan Africa. This was the first study to characterize the HIV care continuum among FSW in Lilongwe, Malawi.From July through September 2014, we used venue-based sampling to enroll 200 adult FSW in Lilongwe, Malawi into a cross-sectional evaluation assessing HIV care continuum outcomes. Seropositive FSW, identified using HIV rapid testing, received rapid CD4 counts in addition to viral loads using dried blood spots. We calculated proportions of HIV-infected FSW who had history of care, were on ART, and had suppressed viral load and we used Poisson regression to estimate the associations of demographic characteristics and transmission risk behaviors with each outcome.HIV seroprevalence was 69% (n = 138). Among all FSW the median age was 24 years (IQR: 22-28). Among the 20% who were newly diagnosed and reported previously testing negative, the median time since last HIV test was 11 months (interquartile range: 3-17). The majority (69%) of HIV-infected FSW had a history of HIV care, 52% reported current ART use, and 45% were virally suppressed. Of the FSW who reported current ART use, 86% were virally suppressed. Transmission risk behaviors were not associated with continuum outcomes.FSW in Lilongwe were predominately young and have a high HIV prevalence. Only half of HIV-infected FSW reported current ART use, but the majority of those on ART were virally suppressed. To reduce ongoing transmission and improve health outcomes, increased HIV testing, care engagement, and ART coverage is urgently needed among FSW. Universal testing and treatment strategies for all FSW in Malawi must be strongly considered. more...

To evaluate the feasibility and effectiveness of dried blood spots (DBS) use for viral load (VL) monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa.We recruited adult antiretroviral therapy (ART) patients from five district hospitals in Malawi. Eligibility reflected anticipated Ministry of Health VL monitoring criteria. Testing was conducted at a central laboratory. Virological failure was defined as >5000 copies/ml. Primary outcomes were program feasibility (timely result availability and patient receipt) and effectiveness (second-line therapy initiation).We enrolled 1,498 participants; 5.9% were failing at baseline. Median time from enrollment to receipt of results was 42 days; 79.6% of participants received results within 3 months. Among participants with confirmed elevated VL, 92.6% initiated second-line therapy; 90.7% were switched within 365 days of VL testing. Nearly one-third (30.8%) of participants with elevated baseline VL had suppressed (4 years were more likely to be failing than participants on therapy 1-4 years (RR 1.7, 95% CI 1.0-2.8); older participants were less likely to be failing (RR 0.95, 95% CI 0.92-0.98). There was no difference in likelihood of failure based on clinical symptoms (RR 1.17, 95% CI 0.65-2.11).DBS for VL monitoring is feasible and effective in real-world clinical settings. Centralized DBS testing may increase access to VL monitoring in remote settings. Programmatic outcomes are encouraging, especially proportion of eligible participants switched to second-line therapy. more...

BackgroundPrograms for integration of family planning into HIV care must recognize current practices and desires among clients to appropriately target and tailor interventions. We sought to evaluate fertility intentions, unintended pregnancy, contraceptive and condom use among a cohort of HIV-infected women seeking family planning services within an antiretroviral therapy (ART) clinic.Methods200 women completed an interviewer-administered questionnaire during enrollment into a prospective contraceptive study at the Lighthouse Clinic, an HIV/ART clinic in Lilongwe, Malawi, between August and December 2010.ResultsMost women (95%) did not desire future pregnancy. Prior reported unintended pregnancy rates were high (69% unplanned and 61% unhappy with timing of last pregnancy). Condom use was inconsistent, even among couples with discordant HIV status, with lack of use often attributed to partner's refusal. Higher education, older age, lower parity and having an HIV negative partner were factors associated with consistent condom usage.DiscussionHigh rates of unintended pregnancy among these women underscore the need for integ rating family planning, sexually transmitted infection (STI) prevention, and HIV services. Contraceptive access and use, including condoms, must be improved with specific efforts to enlist partner support. Messages regarding the importance of condom usage in conjunction with more effective modern contraceptive methods for both infection and pregnancy prevention must continue to be reinforced over the course of ongoing ART treatment. more...

The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy. more...

BACKGROUND:HIV-1 and Plasmodium falciparum malaria cause substantial morbidity in Sub-Saharan Africa, especially as co-infecting pathogens. We examined the relationship between presence of P. falciparum DNA in plasma samples and clinical malaria as well as the impact of atazanavir, an HIV-1 protease inhibitor (PI), on P. falciparum PCR positivity. METHODS:ACTG study A5175 compared two NNRTI-based regimens and one PI-based anti-retroviral (ARV) regimen in antiretroviral therapy naïve participants. We performed nested PCR on plasma samples for the P. falciparum 18s rRNA gene to detect the presence of malaria DNA in 215 of the 221 participants enrolled in Blantyre and Lilongwe, Malawi. We also studied the closest sample preceding the first malaria diagnosis from 102 persons with clinical malaria and randomly selected follow up samples from 88 persons without clinical malaria. RESULTS:PCR positivity was observed in 18 (8%) baseline samples and was not significantly associated with age, sex, screening CD4+ T-cell count, baseline HIV-1 RNA level or co-trimoxazole use within the first 8 weeks. Neither baseline PCR positivity (p = 0.45) nor PCR positivity after initiation of antiretroviral therapy (p = 1.0) were significantly associated with subsequent clinical malaria. Randomization to the PI versus NNRTI ARV regimens was not significantly associated with either PCR positivity (p = 0.5) or clinical malaria (p = 0.609). Clinical malaria was associated with a history of tuberculosis (p = 0.006) and a lower BMI (p = 0.004). CONCLUSION:P. falciparum DNA was detected in 8% of participants at baseline, but was not significantly associated with subsequent development of clinical malaria. HIV PI therapy did not decrease the prevalence of PCR positivity or incidence of clinical disease. more...

Despite Kaposi's sarcoma (KS) being the most prevalent AIDS-associated cancer in resource limited settings, optimal treatment options remain unknown. We assessed whether bleomycin/vincristine compared to vincristine monotherapy was associated with improved treatment outcomes for AIDS-associated KS among patients initiating combination antiretroviral therapy (cART) in Malawi.All patients initiating cART and chemotherapy for AIDS-related KS were identified from an electronic data system from the HIV Lighthouse Clinic from 2002 to 2011. Treatment responses were compared between patients receiving vincristine monotherapy and vincristine/bleomycin. Binomial regression models were implemented to assess probability of tumor improvement for patients receiving vincristine/bleomycin compared to vincristine monotherapy after a complete cycle of chemotherapy (9-10 months). A chi-squared test was used to compare changes in CD4 count after six months of chemotherapy.Of 449 patients with AIDS-associated KS on chemotherapy, 94% received vincristine monotherapy and 6% received bleomycin/vincristine. Distribution of treatment outcomes was different: 29% of patients on vincristine experienced tumor improvement compared to 53% of patients on bleomycin/vincristine. Patients receiving bleomycin/vincristine were 2.25 (95% CI: 1.47, 3.44) times as likely to experience tumor improvement as to those on vincristine monotherapy. This value changed little after adjustment for age and baseline CD4 count: 2.46 (95% CI: 1.57, 3.86). Change in CD4 count was similar for patients receiving vincristine monotherapy and bleomycin/vincristine (p = 0.6).Bleomycin/vincristine for the treatment of AIDS-associated KS was associated with better tumor response compared to vincristine monotherapy without impairing CD4 count recovery. Replication in larger datasets and randomized controlled trials is necessary. more...

BACKGROUND: The Tingathe program utilizes community health workers to improve prevention of mother-to-child transmission (PMTCT) service delivery. We evaluated the impact of antiretroviral (ARV) regimen and maternal CD4+ count on HIV transmission within the Tingathe program in Lilongwe, Malawi. METHODS: We reviewed clinical records of 1088 mother-infant pairs enrolled from March 2009 to March 2011 who completed follow-up to first DNA PCR. Eligibility for antiretroviral treatment (ART) was determined by CD4+ cell count (CD4+) for women not yet on ART. ART-eligible women initiated stavudine-lamivudine-nevirapine. Early ART was defined as ART for ≥14 weeks prior to delivery. For women ineligible for ART, optimal ARV prophylaxis was maternal AZT ≥6 weeks+sdNVP, and infant sdNVP+AZT for 1 week. HIV transmission rates were determined for ARV regimens, and factors associated with vertical transmission were identified using bivariate logistic regression. RESULTS: Transmission rate at first PCR was 4.1%. Pairs receiving suboptimal ARV prophylaxis were more likely to transmit HIV (10.3%, 95% CI, 5.5-18.1%). ART was associated with reduced transmission (1.4%, 95% CI, 0.6-3.0%), with early ART associated with decreased transmission (no transmission), compared to all other treatment groups (p = 0.001). No association was detected between transmission and CD4+ categories (p = 0.337), trimester of pregnancy at enrollment (p = 0.100), or maternal age (p = 0.164). CONCLUSION: Low rates of MTCT of HIV are possible in resource-constrained settings under routine programmatic conditions. No transmissions were observed among women on ART for more than 14 weeks prior to delivery. more...

Despite increasing cancer burden in Malawi, pathology services are limited. We describe operations during the first 20 months of a new pathology laboratory in Lilongwe, with emphasis on cancer diagnoses.We performed a cross-sectional study of specimens from the Kamuzu Central Hospital pathology laboratory between July 1, 2011 and February 28, 2013. Patient and specimen characteristics, and final diagnoses are summarized. Diagnoses were categorized as malignant, premalignant, infectious, other pathology, normal or benign, or nondiagnostic. Patient characteristics associated with premalignancy and malignancy were assessed using logistic regression. Of 2772 specimens, 2758 (99%) with a recorded final diagnosis were included, drawn from 2639 unique patients. Mean age was 38 years and 63% were female. Of those with documented HIV status, 51% had unknown status, and 36% with known status were infected. Histologic specimens comprised 91% of cases, and cytologic specimens 9%. Malignant diagnoses were most common overall (n = 861, 31%). Among cancers, cervical cancer was most common (n = 117, 14%), followed by lymphoma (n = 91, 11%), esophageal cancer (n = 86, 10%), sarcoma excluding Kaposi sarcoma (n = 75, 9%), and breast cancer (n = 61, 7%). HIV status was known for 95 (11%) of malignancies, with HIV prevalence ranging from 9% for breast cancer to 81% for cervical cancer. Increasing age was consistently associated with malignancy [bivariable odds ratio 1.24 per decade increase (95% CI 1.19-1.29) among 2685 patients with known age; multivariable odds ratio 1.33 per decade increase (95% CI 1.14-1.56) among 317 patients with known age, gender, and HIV status], while HIV infection and gender were not.Despite selection and referral bias inherent in these data, a new pathology laboratory in Lilongwe has created a robust platform for cancer care and research. Strategies to effectively capture clinical information for pathologically confirmed cancers can allow these data to complement population-based registration. more...

HIV protease inhibitors (PIs) show antimalarial activity in vitro and in animals. Whether this translates into a clinical benefit in HIV-infected patients residing in malaria-endemic regions is unknown. We studied the incidence of malaria, as defined by blood smear positivity or a positive Plasmodium falciparum histidine-rich protein 2 antigen test, among 444 HIV-infected women initiating antiretroviral treatment (ART) in the OCTANE trial (A5208; ClinicalTrials.gov: NCT00089505). Participants were randomized to treatment with PI-containing vs. PI-sparing ART, and were followed prospectively for ≥48 weeks; 73% also received cotrimoxazole prophylaxis. PI-containing treatment was not associated with protection against malaria in this study population. more...

HIV incidence is higher among pregnant women than their non-pregnant counterparts in some sub-Saharan African settings. Our aims were (1) to estimate HIV incidence during pregnancy and (2) to compare sexual activity between pregnant, postpartum, and non-pregnant women.We examined a retrospective cohort of 1087 women to identify seroconverters using antenatal and labor ward HIV test results. We also conducted a cross-sectional survey, including a quantitative questionnaire (n = 200) and in-depth interviews (n = 20) among women in early pregnancy, late pregnancy, postpartum, and non-pregnancy. Outcomes included measures of sexual activity, reported spouse's risky behavior, and beliefs about abstinence.11 of 1087 women seroconverted during pregnancy yielding a 1% seroconversion risk and an incidence rate of 4.0/100 person years (95% CI 2.2-7.2). The reported sexual activity of the early pregnancy and non-pregnancy groups was similar, but significantly higher than the late pregnancy and postpartum groups (p more...

BackgroundAntiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and findings1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; pConclusionEFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial registrationwww.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary. more...

BackgroundThe Malawian government recently changed its prevention of mother-to-child transmission (PMTCT) regimen and plans to change its first-line antiretroviral therapy (ART) regimen to Tenofovir(TDF)/Lamivudine/Efavirenz as a fixed-dose combination tablet. Implementation could be challenging if baseline creatinine clearance (CrCl) screening were required to assess renal function prior to TDF therapy. Our goal is to determine predictors of CrClMethodologyData on HIV-infected, ART-naïve adults screened for enrollment into 5 HIV clinical trials in Lilongwe, Malawi were combined for a pooled analysis of predictors for CrClResultsThe analysis included 3508 patients with values for creatinine clearance. Most subjects were female (90.6%) with a median age of 26 years (IQR 22-29). The median CD4 cell count was 444 (IQR 298.0-561.0), and 85.2% percent of women in our study were pregnant. Few patients had CrClDiscussionOur findings indicate few patients would be excluded from a TDF-based antiretroviral regimen, suggesting baseline creatinine clearance assessment may not be necessary for implementation. However, in ART settings individuals with low BMI or anemia could potentially be at increased risk for lower CrCl. more...