Efficacy of Two Evidence-Based Alcohol Consumption Interventions on Positive, Negative, and Neutral Days Among Hazardous Alcohol Users Living with HIV in Vietnam.

Social events and stressful settings can be catalysts for alcohol consumption. Motivational enhancement therapy (MET) and cognitive behavioral therapy (CBT) are widely used in alcohol interventions. We assessed how alcohol consumption varied across three types of days (positive/social, negative/stressful, and neutral) among hazardous alcohol users living with HIV in Vietnam. We further evaluated how those consumption patterns changed after two MET/CBT alcohol reduction interventions versus the standard of care (SOC). The 'combined' intervention offered 6 individual sessions and 3 group sessions; the 'brief' intervention offered 2 individual sessions and 2 phone calls. A 30-day timeline follow-back was administered at study visits, detailing daily drinks and events. Days were categorized as neutral, positive/social, or negative/stressful; negative binomial models and generalized estimating equations were used to estimate drinks consumed by type of day at baseline and 12 months. Prior to intervention, more drinks were consumed on positive/social days (5.2 drinks; 95% Confidence Interval [CI]:4.8, 5.7) than negative/stressful (1.5; 95% CI:1.3, 1.9) and neutral days (2.2; 95% CI: 1.9, 2.5). After the brief intervention, drinks consumed decreased on neutral days (ratio: 0.5: 95% CI: 0.4, 0.7). After the combined intervention, drinks consumed decreased on neutral days (ratio: 0.4; 95% CI: 0.3, 0.6), positive/social days (ratio: 0.6; 95% CI: 0.5, 0.7) and negative/stressful days (ratio: 0.3; 95% CI: 0.2, 0.6). No reductions in consumption were observed in the SOC group. Social/positive days had the highest alcohol consumption prior to intervention, and the combined intervention showed the greatest decrease in consumption on those days. CLINICAL TRIAL REGISTRATION: The study is registered at clinicaltrials.gov (NCT02720237).

Promising developments in gonococcal vaccines.

PURPOSE OF REVIEW: While effective vaccines to prevent invasive infections by Neisseria meningitidis have been deployed around the world, development of a vaccine to prevent Neisseria gonorrhoeae has lagged. After multiple failed vaccine candidates, vaccine development for N. gonorrhoeae is showing promise for the first time in several decades. This review highlights recent progress in the field. RECENT FINDINGS: Vaccines containing outer-membrane vesicles (OMV) have been used to manage outbreaks of the serogroup B N. meningitidis in a number of countries. Epidemiologic studies indicate these vaccination campaigns were associated with reductions in reported N. gonorrhoeae infections. Recently, a serogroup B N. meningitidis vaccine containing both recombinant antigens and OMV has been licensed through much of the world. Epidemiologic studies also demonstrate associations between 4CMenB immunization and reduced N. gonorrhoeae infections. Additionally, mathematical modeling studies have begun to identify potential strategies for vaccine deployment to maximize reduction of infections. SUMMARY: After several decades with little progress towards an effective gonococcal vaccine, large observational studies have provided evidence that a new generation of group B N. meningitidis vaccines containing OMV have serendipitously restarted the field. Ongoing clinical trials will soon provide definitive evidence regarding the efficacy of these vaccines in preventing N. gonorrhoeae infection.

Dramatic Shift in the Etiology of Genital Ulcer Disease Among Patients Visiting a Sexually Transmitted Infections Clinic in Lilongwe, Malawi.

BACKGROUND: Genital ulcer diseases (GUDs) are a common syndrome associated with sexually transmitted infections. Genital ulcer diseases increase the risk of HIV transmission, necessitating appropriate diagnosis and treatment. We provide an updated GUD etiology assessment in Malawi to guide diagnostic development and treatment algorithms. METHODS: We enrolled patients 18 years or older presenting with GUD at a sexually transmitted infection clinic in Lilongwe, Malawi, between May and October 2021. We purposively sampled by HIV status. Swabs of ulcers were tested for Treponema pallidum, herpes simplex virus (HSV)-1 and HSV-2, Haemophilus ducreyi, and Chlamydia trachomatis using polymerase chain reaction. Blood was collected for syphilis and HSV-2 serologies and acute HIV testing. Participants were treated per Malawi guidelines. Ulcer resolution (size reduced by >50%) was evaluated 14 days later. RESULTS: Fifty participants enrolled (30 without HIV, 2 with acute HIV infection, 18 with HIV seropositivity; 32 men, 18 women). Forty-six (92%) had an etiology identified. Syphilis was more common among those without HIV (22 of 30 [73%]) than participants with HIV (PWH; 8 of 20 [40%]; P = 0.04). Herpes simplex virus was more common among PWH (11 of 20 [55%]) than participants without (2 of 30 [7%]; P = 0.0002). One-fifth (9 of 50 [18%]) had H. ducreyi. Among those who returned for follow-up (n = 45), 9 (20%) had unresolved ulcers; persistent GUD was slightly more common in PWH (6 of 19 [32%]) than participants without (3 of 26 [12%]; P = 0.14). CONCLUSIONS: We observed a dramatic increase in syphilis ulcer proportion in a population whose GUDs were previously HSV predominant. Observed differences in etiology and resolution by HIV status could play an important role in the ongoing transmission and treatment evaluation of GUD.

Early syphilis in Guangzhou, China: presentation, molecular detection of Treponema pallidum , and genomic sequences in clinical specimens and isolates obtained by rabbit infectivity testing.

Background: The global resurgence of syphilis requires novel prevention strategies. Whole genome sequencing (WGS) of Treponema pallidum ( TPA ) using different specimen types is essential for vaccine development. Methods: Patients with primary (PS) and secondary (SS) syphilis were recruited in Guangzhou, China. We collected ulcer exudates and blood from PS participants, and skin biopsies and blood from SS participants for TPA polA polymerase chain reaction (PCR); ulcer exudates and blood were also used to isolate TPA strains by rabbit infectivity testing (RIT). TPA WGS was performed on 52 ulcer exudates and biopsy specimens and 25 matched rabbit isolates. Results: We enrolled 18 PS and 51 SS participants from December 2019 to March 2022. Among PS participants, TPA DNA was detected in 16 (89%) ulcer exudates and three (17%) blood specimens. Among SS participants, TPA DNA was detected in 50 (98%) skin biopsies and 27 (53%) blood specimens. TP A was isolated from 48 rabbits, with a 71% (12/17) success rate from ulcer exudates and 69% (36/52) from SS bloods. Twenty-three matched SS14 clade genomes were virtually identical, while two Nichols clade pairs had discordant tprK sequences. Forty-two of 52 unique TPA genomes clustered in an SS14 East Asia subgroup, while ten fell into two East Asian Nichols subgroups. Conclusions: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS whole blood, with RIT isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development. Summary: We performed Treponema pallidum molecular detection and genome sequencing from multiple specimens collected from early syphilis patients and isolates obtained by rabbit inoculation. Our results support the use of whole genome sequencing from rabbit isolates to inform syphilis vaccine development.

Clinical and genomic diversity of Treponema pallidum subsp. pallidum: A global, multi-center study of early syphilis to inform vaccine research.

Background: The continuing increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We conducted a multi-center, observational study to explore Treponema pallidum subsp. pallidum ( TPA ) molecular epidemiology essential for vaccine research by analyzing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. Methods: We enrolled patients with primary (PS), secondary (SS) or early latent (ELS) syphilis from clinics in China, Colombia, Malawi and the United States between November 2019 - May 2022. Inclusion criteria included age ≥18 years, and syphilis confirmation by direct detection methods and/or serological testing. TPA detection and WGS were conducted on lesion swabs, skin biopsies/scrapings, whole blood, and/or rabbit-passaged isolates. We compared our WGS data to publicly available genomes, and analysed TPA populations to identify mutations associated with lineage and geography. Findings: We screened 2,820 patients and enrolled 233 participants - 77 (33%) with PS, 154 (66%) with SS, and two (1%) with ELS. Median age of participants was 28; 66% were cis -gender male, of which 43% reported identifying as "gay", "bisexual", or "other sexuality". Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants demonstrated a predominance of SS14-lineage strains with geographic clustering. Phylogenomic analysis confirmed that Nichols-lineage strains are more genetically diverse than SS14-lineage strains and cluster into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models demonstrated population-specific substitutions, some in outer membrane proteins (OMPs) of interest. Interpretation: Our study involving participants from four countries substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains will be vital for vaccine development and improved understanding of syphilis pathogenesis on a population level. Funding: National Institutes of Health, Bill and Melinda Gates Foundation.

HIV and urethritis: time required for antiretroviral therapy to suppress HIV in semen.

OBJECTIVES: To examine the time required to suppress HIV in the genital tract with antiretroviral therapy (ART) in men with urethritis. DESIGN: An observational cohort study. METHODS: Men with HIV and urethritis not on ART were enrolled at an STI clinic in Malawi and offered to initiate ART. Blood and semen samples were collected pretreatment and at 1, 2, 4, 8, 12 and 24 weeks posturethritis treatment. Median viral loads (VLs) were calculated by ART initiation groups: 'within 1 week', 'between 1 and 4 weeks' and 'no ART before 4 weeks', based on the men's choice about whether or not to initiate ART. The presence of ART at each visit was confirmed by bioanalytical methods. FINDINGS: Between January 2017 and November 2018, 74 men presented with urethritis and HIV and were confirmed ART naive. The median age was 32 years. Forty-one (55% of men) initiated ART within 1 week; 12 (16%) between 1 and 4 weeks; and 21 (28%) did not initiate ART by week 4. Within the 1 week group, median VL was suppressed within 4 weeks in both semen and blood. Among the 1-4 weeks group, VL was suppressed within 4 weeks in semen and 5 weeks in blood. Among the no ART before 4 weeks group, VL in semen declined within the first 4 weeks but remained unsuppressed through week 24, and there was no significant decline in blood HIV. CONCLUSION: Treatment of urethritis and prompt initiation of ART with counseling for safer sex for at least one month is a critical measure to reduce transmission of HIV.

Characterizing Network-Based HIV Testing Interventions to Guide HIV Testing and Contact Tracing at STI Clinics in Lilongwe, Malawi.

BACKGROUND: Understanding heterogeneity across patients in effectiveness of network-based HIV testing interventions may optimize testing and contact tracing strategies, expediting linkage to therapy or prevention for contacts of persons with HIV (PWH). SETTING: We analyzed data from a randomized controlled trial of a combination intervention comprising acute HIV testing, contract partner notification (cPN), and social contact referral conducted among PWH at 2 STI clinics in Lilongwe, Malawi, between 2015 and 2019. METHODS: We used binomial regression to estimate the effect of the combination intervention vs. passive PN (pPN) on having any (1) contact, (2) newly HIV-diagnosed contact, and (3) HIV-negative contact present to the clinic, overall and by referring participant characteristics. We repeated analyses comparing cPN alone with pPN. RESULTS: The combination intervention effect on having any presenting contact was greater among referring women than men [prevalence difference (PD): 0.17 vs. 0.10] and among previously vs. newly HIV-diagnosed referring persons (PD: 0.20 vs. 0.11). Differences by sex and HIV diagnosis status were similar in cPN vs. pPN analyses. There were no notable differences in the intervention effect on newly HIV-diagnosed referrals by referring participant characteristics. Intervention impact on having HIV-negative presenting contacts was greater among younger vs. older referring persons and among those with >1 vs. ≤1 recent sex partner. Effect differences by age were similar for cPN vs. pPN. CONCLUSION: Our intervention package may be particularly efficacious in eliciting referrals from women and previously diagnosed persons. When the combination intervention is infeasible, cPN alone may be beneficial for these populations.

Genomic surveillance and antimicrobial resistance determinants in Neisseria gonorrhoeae isolates from Uganda, Malawi and South Africa, 2015-20.

OBJECTIVES: Global antimicrobial resistance (AMR) surveillance in Neisseria gonorrhoeae is essential. In 2017-18, only five (10.6%) countries in the WHO African Region reported to the WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP). Genomics enhances our understanding of gonococcal populations nationally and internationally, including AMR strain transmission; however, genomic studies from Africa are extremely scarce. We describe the gonococcal genomic lineages/sublineages, including AMR determinants, and baseline genomic diversity among strains in Uganda, Malawi and South Africa, 2015-20, and compare with sequences from Kenya and Burkina Faso. METHODS: Gonococcal isolates cultured in Uganda (n = 433), Malawi (n = 154) and South Africa (n = 99) in 2015-20 were genome-sequenced. MICs were determined using ETEST. Sequences of isolates from Kenya (n = 159), Burkina Faso (n = 52) and the 2016 WHO reference strains (n = 14) were included in the analysis. RESULTS: Resistance to ciprofloxacin was high in all countries (57.1%-100%). All isolates were susceptible to ceftriaxone, cefixime and spectinomycin, and 99.9% were susceptible to azithromycin. AMR determinants for ciprofloxacin, benzylpenicillin and tetracycline were common, but rare for cephalosporins and azithromycin. Most isolates belonged to the more antimicrobial-susceptible lineage B (n = 780) compared with the AMR lineage A (n = 141), and limited geographical phylogenomic signal was observed. CONCLUSIONS: We report the first multi-country gonococcal genomic comparison from Africa, which will support the WHO GASP and WHO enhanced GASP (EGASP). The high prevalence of resistance to ciprofloxacin (and empirical use continues), tetracycline and benzylpenicillin, and the emerging resistance determinants for azithromycin show it is imperative to strengthen the gonococcal AMR surveillance, ideally including genomics, in African countries.

Mortality by Admission Diagnosis in Children 1-60 Months of Age Admitted to a Tertiary Care Government Hospital in Malawi.

Diagnosis-specific mortality is a measure of pediatric healthcare quality that has been incompletely studied in sub-Saharan African hospitals. Identifying the mortality rates of multiple conditions at the same hospital may allow leaders to better target areas for intervention. In this secondary analysis of routinely collected data, we investigated hospital mortality by admission diagnosis in children aged 1-60 months admitted to a tertiary care government referral hospital in Malawi between October 2017 and June 2020. The mortality rate by diagnosis was calculated as the number of deaths among children admitted with a diagnosis divided by the number of children admitted with the same diagnosis. There were 24,452 admitted children eligible for analysis. Discharge disposition was recorded in 94.2% of patients, and 4.0% (N = 977) died in the hospital. The most frequent diagnoses among admissions and deaths were pneumonia/bronchiolitis, malaria, and sepsis. The highest mortality rates by diagnosis were found in surgical conditions (16.1%; 95% CI: 12.0-20.3), malnutrition (15.8%; 95% CI: 13.6-18.0), and congenital heart disease (14.5%; 95% CI: 9.9-19.2). Diagnoses with the highest mortality rates were alike in their need for significant human and material resources for medical care. Improving mortality in this population will require sustained capacity building in conjunction with targeted quality improvement initiatives against both common and deadly diseases.

Depression, Alcohol Use, and Sexual Behaviors by HIV Infection Stage and Diagnosis Timing Among STI Clinic Patients in Lilongwe, Malawi.

Understanding depression, alcohol use, and sexual behaviors according to HIV infection stage and diagnosis timing is important for HIV prevention efforts. We enrolled persons with recent infection and diagnosis (i.e., acute HIV infection (AHI) (n = 92) persons newly diagnosed seropositive (n = 360)) and persons previously diagnosed with HIV (n = 190) into a randomized controlled trial in Lilongwe, Malawi (N = 641) and estimated the prevalence of probable depression (Patient Health Questionnaire-9 ≥ 5), hazardous alcohol use (Alcohol Use Disorder Identification Test-C: men ≥ 4; women ≥ 3), and sexual behaviors (transactional sex, condomless sex). Compared with previously diagnosed participants, participants newly seropositive and those with AHI reported a higher proportion of probable depression (7%, 27%, 38%; AHI/Previous: Table Probability: 0.02, p < 0.01; AHI/New: Table Probability: <0.01, p < 0.01), hazardous alcohol use (8%, 18%, 29%; AHI/Previous and AHI/New: Table Probability: <0.01, p < 0.01), and transactional sex (5%, 14%, 20%; AHI/Previous: Table Probability: <0.01, p < 0.01; AHI/New: Table Probability: 0.06, p = 0.24), respectively. HIV prevention services addressing mental health and alcohol misuse may be particularly beneficial for persons with recent HIV infection and or diagnosis.

Kusankha Pamodzi: Health Care Decision-Making Preferences Among Patients with Cancer in Malawi.

Background: Oncology teams are encouraged to include patient preferences and goals of care in determining appropriate treatment courses. There are no existing data from Malawi exploring decision-making preferences among cancer patients. Methods: In the oncology clinic in Lilongwe, Malawi, 50 patients were surveyed for decision making. Results: Most participants (70%, n = 35) preferred to engage in shared decision making regarding cancer treatment. About half (52%, n = 24) did not feel that their medical team involved them in decision making and 64% (n = 32) felt that they were never or only sometimes listened to by the medical team. Nearly all (94%, n = 47) preferred to have their medical team inform them how likely treatments are to lead to cure. Conclusions: Shared decision making was the preferred mode of treatment decision making by the majority of the surveyed cancer patients in Malawi. Cancer patients in Malawi may have similar preferences to cancer patients in other low-resource settings regarding decision making and communication.

Phosphatidylethanol and self-reported alcohol consumption among people living with HIV in Thai Nguyen, Vietnam.

BACKGROUND: Phosphatidylethanol (PEth) is a biomarker for recent alcohol consumption that would ideally validate self-reported alcohol consumption behaviors. We assessed the relationship between PEth and several self-reported alcohol consumption metrics among hazardous alcohol users living with HIV in Vietnam. METHODS: Participants in a three-arm randomized controlled trial assessing two alcohol interventions reported recent alcohol consumption on a 30-day timeline follow-back interview and had a PEth assessment at enrollment, 3 months, and 12 months of the study follow-up. We examined the relationship between self-reported alcohol consumption and quantitative PEth results using Spearman rank correlation and receiver-operating characteristic (ROC) curves to calculate the area under the curve (AUC). We assessed associations between categorical PEth results and self-reported drinking behaviors using prevalence ratios calculated with regression models and generalized estimating equations. RESULTS: Among 1221 study visits (n = 439 participants; 425 (97%) men), the median PEth result was 71 ng/mL (Interquartile range (IQR): 20, 212), and participants reported a median of 11 (IQR: 4, 24) drinking days and 25 (IQR: 8, 71) standard drinks in the previous 28 days. Quantitative PEth results were moderately correlated with drinking days (ρ = 0.26-0.35) and standard drinks consumed (ρ = 0.23-0.38) in the same period. AUCs ranged from 0.54 (any binge drinking in the past 28 days) to 0.82 (any alcohol consumed in the past 21 days). Positive PEth results (≥50 ng/mL) were 2.24 (95% Confidence Interval [CI]: 1.49, 3.35) times as prevalent among participants who reported drinking in the previous 28 days compared with those who did not. CONCLUSIONS: Although PEth values and self-reported alcohol use were correlated, the observed associations were modest. Additional research into the dynamics of PEth production and elimination is warranted across diverse populations to better understand how PEth assessments can best be integrated into research and clinical care.

Integrating Enhanced HIV Pre-exposure Prophylaxis Into a Sexually Transmitted Infection Clinic in Lilongwe: Protocol for a Prospective Cohort Study.

BACKGROUND: Pre-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. OBJECTIVE: This 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. METHODS: The 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. RESULTS: Enrollment 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. CONCLUSIONS: This 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 REGISTRATION: ClinicalTrials.gov NCT05307991; https://clinicaltrials.gov/ct2/show/NCT05307991. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37395.

Implementation and Evaluation of Educational Videos to Improve Cancer Knowledge and Patient Empowerment.

PURPOSE: Low health literacy is a leading cause of treatment abandonment among patients receiving cancer care at Kamuzu Central Hospital (KCH) in Malawi. METHODS: We developed cancer educational videos featuring Malawian providers and played them in the KCH oncology clinic. The videos addressed cancer-related topics, including disease biology, common myths, diagnostic procedures, treatment, side effects, and survivorship. After 6 months of implementation, we compared results from 50 pre- and postintervention surveys to assess change in cancer knowledge and care experience. RESULTS: Both pre- and postintervention cancer knowledge were good: a median of nine questions were answered correctly of 11 in both assessments. Despite the intervention, most continued to incorrectly identify cancer as an infection (pre: n = 26, 52%; post: n = 25, 50%; P = 1.0), although improvements were observed in patients' knowledge of correct actions for fever at home (pre: n = 38, 76%; post: n = 43, 86%; P = .31). Care experiences were overall good. Postintervention results indicate that more patients felt always listened to by their providers (pre: n = 18, 36%; post: n = 29, 58%; P < .01). However, we also noted a higher rate of patient dissatisfaction of care as more patients felt that they could not understand chemotherapy counseling (pre: n = 11, 22%; post: n = 22, 44%; P < .01). Assessments of video satisfaction indicate that patients found the videos very helpful in terms of understanding their disease (n = 47, 96%) and side effects (n = 48, 98%) and felt empowered to speak up with their providers (n = 46, 96%). CONCLUSION: Standardized education materials for patients that can be feasibly implemented throughout sub-Saharan Africa are urgently needed. Cancer educational videos are a low-cost way to educate and empower patients with cancer in resource-constrained settings although in-person discussions remain a crucial part of care.

Brief Report: Blood and Genital Fluid Viral Load Trajectories Among Treated and Untreated Persons With Acute HIV Infection in Malawi.

BACKGROUND: Persons with acute HIV infection (AHI) are highly infectious and responsible for a disproportionate share of incident infections. Immediate antiretroviral therapy (ART) rapidly reduces blood viral loads (VLs), but genital VLs after ART initiation during AHI are less well described. SETTING: Lilongwe, Malawi, 2012-2014. METHODS: HIV-seronegative and HIV-serodiscordant persons aged ≥18 years were screened for AHI (RNA positive) and randomized to standard of care, behavioral intervention, or behavioral intervention plus short-term ART (raltegravir/emtricitabine/tenofovir) (1:2:2). Persons who were ART eligible under Malawi guidelines could receive first-line therapy. Blood and genital VLs were assessed at weeks 1, 4, 8, and 12. Fisher's Exact test was used to compare viral suppression by ART status. RESULTS: Overall, 46 persons with AHI were enrolled; of whom, 17 started ART within 12 weeks. Median blood VL at AHI diagnosis was 836,115 copies/mL. At week 12, 7% (1/14) of those who initiated ART had a blood VL of ≥400 copies/mL, compared with 100% (23/23; P < 0.0001) of those who did not initiate ART (median VL: 61,605 copies/mL). Median genital VL at week 1 was 772 copies/mL, with 13 of 22 (59%) having VL of ≥400 copies/mL. At week 12, 0 of 10 (0%) of those who initiated ART had genital VL of ≥400 copies/mL, compared with 7 of 15 (47%) of those who did not initiate ART (P = 0.02). CONCLUSION: Although highly correlated, VLs in blood and genital fluids occupy discrete biological compartments with distinct virologic dynamics. Our results corroborate the dramatic reduction in both compartments after ART initiation. Increasing AHI screening and rapidly initiating treatment is key to interrupting transmission.

Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi.

BACKGROUND: Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. METHODS: Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure. RESULTS: Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 µg/mL; 111 (78.7%), MIC = 4 µg/mL; and 28 (19.9%), MIC = 8 µg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 µg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism). CONCLUSIONS: Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.

HIV and STI prevalence and testing history among men who have sex with men in Hanoi, Vietnam.

BACKGROUND: HIV and other sexually transmitted infections (STIs) have disproportionately affected communities of men who have sex with men (MSM). We describe HIV and STI prevalence and testing patterns among urban Vietnamese MSM. METHODS: We conducted a cross-sectional community-based study of MSM in Hanoi, Vietnam in 2016. Participants self-reported experiences of social stigma in healthcare settings and previous HIV and STI testing. STI testing included HIV, herpes simplex virus-2 (HSV-2), syphilis, gonorrhea, and chlamydia. RESULTS: 205 MSM participated in the study. STI prevalence was HIV (10%), HSV-2 (4%), syphilis (13%), gonorrhea (34%), and chlamydia (19%). More than half (55%) of participants tested positive for at least one STI. Most participants had been previously tested for HIV or another STI (72%), with 24% previously receiving a positive result. Perceived and enacted social stigma in healthcare contexts was negatively associated with previous HIV or STI testing (adjusted prevalence odds ratio (aPOR): 0.22; 95% confidence interval (CI): 0.10-0.48). DISCUSSION: High prevalence of STIs was observed among Vietnamese MSM, and perceived and enacted stigma was related to HIV and STI testing. Our findings reaffirm the importance of regular STI screening among this population as well as additional outreach to promote safe HIV and STI healthcare engagement.

A randomized controlled trial evaluating combination detection of HIV in Malawian sexually transmitted infections clinics.

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

Syndromes Associated with Sexually Transmitted Infections in Lilongwe, Malawi: Burden and Trends, 2006 to 2015.

ABSTRACT: Monitoring the burden of and trends in sexually transmitted infection syndromes is useful in informing syndromic management guidelines. Among sexually transmitted infection clinic patients in Lilongwe, Malawi, between 2006 and 2015, genital discharge, lower abdominal pain, and genital ulcer syndromes were common. Prevalence of most syndromes remained stable during the 10-year period.

Outcomes From Re-Treatment and Cerebrospinal Fluid Analyses in Patients With Syphilis Who Had Serological Nonresponse or Lack of Seroreversion After Initial Therapy.

BACKGROUND: We conducted an observational study to determine whether patients with syphilis who do not demonstrate serological cure or lack of seroreversion in nontreponemal (NT) antibody titers after initial therapy benefit from re-treatment and cerebrospinal fluid (CSF) analysis. METHODS: We enrolled patients with syphilis from sexually transmitted disease clinics in Guangzhou, China, who had persistent NT titers after therapy. Serological nonresponse was defined as a <4-fold decline in baseline NT titers after therapy. Lack of seroreversion was defined as demonstrating a ≥4-fold NT titer decline but without seroreversion to negative, or having persistent low-level titers (i.e., 1:1-1:2) after therapy. After consent, we abstracted medical record data regarding syphilis diagnoses, initial and re-treatment regimens, and serological outcomes. Nontreponemal titers were obtained from participants at enrollment and follow-up. We evaluated CSF findings among a subgroup of participants relative to re-treatment. RESULTS: From March 2012 to February 2016, we enrolled 135 HIV-negative patients with syphilis with persistent NT titers after initial therapy. Among 116 participants with ≥12 months of follow-up, 60 (52%) received re-treatment of syphilis. Overall, there were no significant differences in serological response between those who were re-treated and those who were not among serological nonresponders (29% vs. 27%; P = 1.0) or among participants without seroconversion (41% vs. 37%; P = 0.8). Of 60 participants who underwent CSF analyses, 8 (13%) had CSF abnormalities, but only 2 (3%) met the neurosyphilis criteria after re-treatment. CONCLUSIONS: Most HIV-negative patients with syphilis who have serological nonresponse or lack of seroreversion after therapy do not benefit from re-treatment in the short term, and neurosyphilis is uncommon.