Delivering effective, comprehensive, multi-exercise component cardiac rehabilitation (CR) for chronic heart failure patients in low resource settings in sub-Saharan Africa: Queen Elizabeth Central Hospital-(QECH-CR) randomised CR study, Malawi.

BACKGROUND: The delivery of Cardiac Rehabilitation (CR) and attaining evidence-based treatment goals are challenging in developing countries, such as Malawi. The aims of this study were to (i) assess the effects of exercise training/ CR programme on cardiorespiratory and functional capacity of patients with chronic heart failure (CHF), and (ii) examine the effectiveness of a novel, hybrid CR delivery using integrated supervised hospital- and home-based caregiver approaches. METHODS: A pre-registered (UMIN000045380), randomised controlled trial of CR exercise therapy in patients with CHF was conducted between September 2021 and May 2022. Sixty CHF participants were randomly assigned into a parallel design-exercise therapy (ET) (n = 30) or standard of care (n = 30) groups. Resting hemodynamics, oxygen saturation, distance walked in six-minutes (6MWD) and estimated peak oxygen consumption (VO2 peak) constituted the outcome measures. The exercise group received supervised, group, circuit-based ET once weekly within the hospital setting and prescribed home-based exercise twice weekly for 12 weeks. Participants in both arms received a group-based, health behaviour change targeted education (usual care) at baseline, 8-, 12- and 16-weeks. RESULTS: Most of the participants were female (57%) with a mean age of 51.9 ±15.7 years. Sixty-five percent (65%) were in New York Heart Association class III, mostly with preserved left ventricular ejection fraction (HFpEF) (mean Left Ventricular Ejection Fraction 52.9 ±10.6%). The 12-weeks ET led to significant reductions in resting haemodynamic measures (all P <0.05). The ET showed significantly higher improvements in the 6MWD (103.6 versus 13.9 m, p<0.001) and VO2 peak (3.0 versus 0.4 ml·kg-1·min-1, p <0.001). Significant improvements in 6MWD and VO2 peak (both p<0.001), in favour of ET, were also observed across all follow-up timepoints. CONCLUSION: This novel, randomised, hybrid ET-based CR, delivered to mainly HFpEF patients using an integrated hospital- and home-based approach effectively improved exercise tolerance, cardiorespiratory fitness capacities and reduced perceived exertion in a resource-limited setting.

Factors associated with reactogenicity to an investigational HIV vaccine regimen in HIV vaccine trials network 702.

BACKGROUND: Reactogenicity informs vaccine safety, and may influence vaccine uptake. We evaluated factors associated with reactogenicity in HVTN 702, a typical HIV vaccine efficacy trial with multiple doses and products. METHODS: HVTN 702, a phase 2b/3 double-blind placebo-controlled trial, randomized 5404 African participants aged 18-35 years without HIV to placebo, or ALVAC-HIV (vCP2438) at months 0, 1 and ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59 at months 3, 6, 12 and 18. Using multivariate logistic regression, we evaluated associations between reactogenicity with clinical, sociodemographic and laboratory variables. RESULTS: More vaccine than placebo-recipients reported local symptoms (all p < 0.001), arthralgia (p = 0.008), chills (p = 0.012) and myalgia (p < 0.001). Reactogenicity was associated with female sex at birth (ORv = 2.50, ORp = 1.81, both p < 0.001) and geographic region. Amongst vaccine-recipients, each year of age was associated with 3 % increase in reactogenicity (OR = 1.03, p = 0.002). CONCLUSION: Vaccine receipt, female sex at birth, older age, and region may affect reactogenicity.

A woman with focal neurological deficit following treatment for cholera.

A 41-year old woman was treated for cholera at one of the health centers in Blantyre. Two days after discharge from the treatment unit, she developed weakness of all 4 limbs and difficulties with speech. She was referred to the Queen Elizabeth Central Hospital. A CT scan of the brain showed hypodense lesions in the pons. A diagnosis of central pontine myelinolysis was made. She recovered slowly and was discharged from hospital 17 days after admission.

Uptake of diabetic retinopathy screening at a secondary level facility in Malawi.

Diabetic retinopathy (DR) is a common microvascular complication of long-standing diabetes mellitus (DM). DR screening is a cost-effective intervention for preventing blindness from DR. We conducted a cross-sectional study to investigate the uptake and the predictors of uptake of annual DR screening in an opportunistic DR screening programme at a secondary-level diabetes clinic in Southern Malawi. Consecutive patients were interviewed using a structured questionnaire to record their demographic characteristics, medical details and data regarding; the frequency of clinic visits, knowledge of existence of DR screening services and a history of referral for DR screening in the prior one year. Univariate binary logistic regression was used to investigate predictors of DR screening uptake over the prior one year. Explanatory variables that had a P-value of < 0.1 were included into a multivariate logistic regression model. All variables that had a p-value of <0.05 were considered to be statistically significant. We recruited 230 participants over three months with a median age of 52.5 years (IQR 18-84) and a median duration of diabetes of 4 years (IQR 1-7). The average interval of clinic visits was 1.2 months (SD ± 0.43) and only 59.1% (n = 139) of the participants were aware of the existence of diabetic retinopathy screening services at the facility. The uptake for DR screening over one year was 20% (n = 46). The strongest predictors of uptake on univariate analysis were awareness of the existence of DR screening services (OR 10.05, P <0.001) and a history of being referred for DR screening (OR 9.02, P <0.001) and these remained significant on multivariable analysis. Interventions to improve uptake for DR screening should promote referral of patients for DR screening and strengthen knowledge about the need and availability of DR screening services.

Quality of life among type 2 diabetes mellitus patients at Kamuzu Central Hospital in Lilongwe, Malawi: A mixed-methods study.

Type II diabetes mellitus (T2DM) significantly impacts quality of life (QoL) yet data among these patients in Malawi are lacking. This study was conducted to assess QoL among patients with T2DM. A mixed-method cross-section study was conducted at Kamuzu Central Hospital (KCH), Lilongwe, Malawi. Data collection was done using a modified diabetes quality of life (MDQoL)-17 questionnaire for quantitative data while in-depth interviews and diary methods were used for qualitative data. Demographic data were summarized using descriptive statistics and inferential statistics using t-tests and ANOVA. Thematic analysis was utilized for qualitative data. A sample of 339 participants (mean age 50.3±15.5) was recruited. Overall, the mean QoL score was moderate (mean QoL 63.91±19.54). Those on health insurance had better QoL (QoL 76.71, C.I. 69.22-84.19, p-value 0.005) compared to those without health insurance. Furthermore, the absence of comorbidities was associated with having better QoL (QoL 71.18, C.I. 66.69-75.67, p-value < 0.0001). Qualitatively, T2DM was associated with patients' health status, increased stress levels, and loss of independence. There were QoL-promoting factors among T2DM patients such as diabetes health talks, having a supportive family, and following hospital advice. Inhibiting factors include drug shortages, societal perceptions, a sedentary lifestyle, stress, and despising hospital advice. Overall QoL in patients with T2DM receiving treatment at KCH is moderate. QoL of patients with T2DM is influenced by interrelated factors which require multidisciplinary team care to optimize the QoL among these patients. Health workers need to adopt a holistic approach when treating patients with T2DM, such as managing comorbidities and including assessment of QoL, behavioral change measures like physical exercises, and a healthy diet.

Prospective pilot study on the relationship between seminal HIV-1 shedding and genital schistosomiasis in men receiving antiretroviral therapy along Lake Malawi.

Male genital schistosomiasis (MGS) is hypothesized to increase seminal shedding of HIV-1. This prospective pilot study assessed seminal HIV-1 RNA shedding in men on long-term ART with and without a diagnosis of MGS. Study visits occurred at 0, 1, 3, 6 and 12 months. MGS was diagnosed by egg positivity on semen microscopy or PCR of seminal sediment. After optimization of the HIV-RNA assay, we examined 72 paired plasma and semen samples collected from 31 men (15 with and 16 without MGS) over 12 months. HIV-1 RNA was detected in 7/72 (9.7%) seminal samples and 25/72 (34.7%) plasma samples. When comparing sample pairs, 5/72 (6.9%) showed HIV-1 RNA detection only in the seminal sample. Overall, 3/31 (9.7%) participants, all with MGS, had detectable HIV-1 RNA in semen while plasma HIV-1 RNA was undetectable (< 22 copies/mL), with seminal levels ranging up to 400 copies/mL. Two participants showing HIV-1 RNA in seminal fluid from the MGS-negative group also had concomitant HIV-1 RNA detection in plasma. The findings suggest that MGS can be associated with low-level HIV-1 RNA shedding despite virologically suppressive ART. Further studies are warranted to confirm these observations and assess its implications.

Mycobacterium tuberculosis disease associates with higher HIV-1-specific antibody responses.

Mycobacterium tuberculosis (Mtb) is the most common infection among people with HIV (PWH). Mtb disease-associated inflammation could affect HIV-directed immune responses in PWH. We show that HIV antibodies are broader and more potent in PWH in the presence as compared to the absence of Mtb disease. With co-existing Mtb disease, the virus in PWH also encounters unique antibody selection pressure. The Mtb-linked HIV antibody enhancement associates with specific mediators important for B cell and antibody development. This Mtb humoral augmentation does not occur due to cross-reactivity, a generalized increase in all antibodies, or differences in duration or amount of antigen exposure. We speculate that the co-localization of Mtb and HIV in lymphatic tissues leads to the emergence of potent HIV antibodies. PWH's Mtb disease status has implications for the future use of HIV broadly neutralizing antibodies as prophylaxis or treatment and the induction of better humoral immunity.

The diagnostic performance of Xpert MTB/RIF Ultra on Pericardial, Pleural and Ascitic cohort study fluids for diagnosis of extra-pulmonary Tuberculosis at a referral hospital in Malawi.

Background: Extra-pulmonary tuberculosis (EPTB) accounts for 15% of the 1.4 million patients with TB notified in 2019. EPTB carries a high risk of mortality and so early diagnosis and treatment are important to reduce this risk. Diagnosis of EPTB in low- and middle-income countries is challenging. This study investigated the diagnostic performance of Xpert MTB Ultra for the diagnosis of EPTB (pericardial, pleural, and ascitic fluid) in adults at a referral hospital in Malawi. Methods: Adults with suspected extra-pulmonary TB were screened for evidence of extra-pulmonary fluid and tested for TB using Xpert MTB Ultra, mycobacterial culture, and a Focused Abdominal Sonography in HIV-associated TB (FASH scan). The diagnostic performance of the Xpert MTB Ultra was compared to mycobacterial culture and a composite reference standard defined as a positive FASH scan or a positive mycobacterial culture or a clinical TB diagnosis (constitutional symptoms not otherwise explained with response to empirical TB treatment). Results: There were 174 patients recruited: 99/174 (57%) pleural, 70/174 (40%) ascitic and 5/174 (3%) pericardial. Overall, 10/174 (6%) had bacteriologically confirmed TB and 30/174 (17%) were started on TB treatment based on a positive FASH scan or a clinical TB diagnosis. The sensitivity and specificity of Xpert ultra compared to culture was 83% (95%CI:36%-100%) and 98% (95%CI:94%-99%), respectively. Compared to the composite reference standard, the sensitivity of Xpert Ultra was 17% (95%CI:7%-34%) and specificity was 98% (95%CI:94%-100%). Conclusion: Xpert MTB Ultra provides good diagnostic performance on pleural, pericardial and ascitic fluid with reference to mycobacterial culture. Improved EPTB diagnostic tests are required to improve patient outcomes. We recommend larger multi-centre studies to corroborate our findings.

High prevalence of dyslipidaemia among persons with diabetes mellitus and hypertension at a tertiary hospital in Blantyre, Malawi.

BACKGROUND: Dyslipidaemia drives the process of atherosclerosis, and hence a significant modifiable risk factor complicating hypertension and diabetes. In Malawi, the prevalence, screening and management of dyslipidaemia among persons with diabetes mellitus have not been reported. This study aimed to investigate the prevalence, biochemical characteristics, screening and management practices for dyslipidaemia among persons with diabetes mellitus, hypertension, and diabetes mellitus and hypertension comorbidity at Queen Elizabeth Central hospital in Blantyre, Malawi. METHODS: This was a cross-sectional study conducted in 2021. A total of 256 adult participants (diabetes mellitus = 100); hypertension = 100; both conditions = 56) were included. Medical data and anthropometric measurements were recorded. Blood samples were analysed for HbA1C and serum lipids. Associated risk factors for dyslipidaemia were also assessed. RESULTS: Dyslipidaemia was prevalent in 58%, 55%, and 70% of participants with diabetes mellitus, hypertension, and both conditions. Low-density lipoprotein cholesterol (LDL-C) dyslipidaemia was the most common in all participant groups. Participants with both diabetes and hypertension had 2.4 times (95% CI 1.2-4.6) increased risk of LDL-C dyslipidaemia than those with diabetes alone (p < 0.02). Being overweight or obese and age over 30 years were risk factors for dyslipidaemia in participants with diabetes mellitus alone (OR 1.3 (95% CI 1.1-1.6), p < 0.04, and OR 2.2 (95% CI 1.2-4.7) (p < 0.01), respectively. Overweight and obesity predicted LDL-C dyslipidaemia in hypertensive patients (OR 3.5 (95% CI 1.2-9.9) p < 0.001). Poorly controlled hypertension and the use of beta-blockers and thiazide diuretics predicted dyslipidaemia among patients with both diabetes mellitus and hypertension (OR 6.50 CI 1.45-29.19; and OR 5.20 CI 1.16-23.36 respectively). None of the participants had a lipogram performed before the study or were on lipid-lowering therapy. CONCLUSIONS: Dyslipidaemia with LDL-C derangement was highly prevalent, especially in individuals with both diabetes mellitus and hypertension, and there was absent use of lipid-lowering therapy. Screening and managing dyslipidaemia should be reinforced to reduce the risk of cardiovascular complications in this population at increased risk.

An audit of Heart failure management among ambulatory adult patients at Queen Elizabeth Central Hospital (QECH), Malawi.

Background: There are limited data on the clinical characteristics and use of guideline directed medical therapy among patients with heart failure in Malawi. We conducted a study to assess patient characteristics and clinical management given to heart failure patients at Queen Elizabeth Central hospital in Malawi. Methods: In a cross sectional study, patients with a diagnosis of heart failure who were followed up in the adult chest clinic at QECH were recruited to ascertain their characteristics and the therapy they were receiving. Echocardiograms and electrocardiograms were performed to identify abnormalities. Results: A total of 79 patients were recruited and 62% (49 out of 79) were female. The median age was 60 years (IQR 40.5-70.5). Most patients were hypertensive with NYHA (New York Heart Association) class I and II symptoms. Left ventricular(LV) systolic dysfunction was found in 55% (36 out of 65), with 68% (39 out of 65) having features of left ventricular remodeling. Most patients were on at least a single neurohormonal drug with 77% (61 out of 79) on ACEI (angiotensin converting enzyme inhibitor), 52% (42 out of 79) on a beta blocker and 34%(27 out of 79) on aldosterone antagonists. The recommended doses of medications were achieved in 14% (9 out 61), 24% (10 out 42), 22% (6 out of 27) on ACEI, beta blockers and aldosterone antagonists respectively. Conclusions: Hypertension is the commonest comorbidity in patients with heart failure, who are mostly females with NYHA class I or II symptoms. Most had LV remodeling changes and are on at least one neurohormonal antagonist but most remain sub optimally treated.

Isoniazid Adherence Reduces Mortality and Incident Tuberculosis at 96 Weeks Among Adults Initiating Antiretroviral Therapy With Advanced Human Immunodeficiency Virus in Multiple High-Burden Settings.

Background: People with human immunodeficiency virus (HIV) and advanced immunosuppression initiating antiretroviral therapy (ART) remain vulnerable to tuberculosis (TB) and early mortality. To improve early survival, isoniazid preventive therapy (IPT) or empiric TB treatment have been evaluated; however, their benefit on longer-term outcomes warrants investigation. Methods: We present a 96-week preplanned secondary analysis among 850 ART-naive outpatients (≥13 years) enrolled in a multicountry, randomized trial of efavirenz-containing ART plus either 6-month IPT (n = 426) or empiric 4-drug TB treatment (n = 424). Inclusion criteria were CD4 count <50 cells/mm3 and no confirmed or probable TB. Death and incident TB were compared by strategy arm using the Kaplan-Meier method. The impact of self-reported adherence (calculated as the proportion of 100% adherence) was assessed using Cox-proportional hazards models. Results: By 96 weeks, 85 deaths and 63 TB events occurred. Kaplan-Meier estimated mortality (10.1% vs 10.5%; P = .86) and time-to-death (P = .77) did not differ by arm. Empiric had higher TB risk (6.1% vs 2.7%; risk difference, -3.4% [95% confidence interval, -6.2% to -0.6%]; P = .02) and shorter time to TB (P = .02) than IPT. Tuberculosis medication adherence lowered the hazards of death by ≥23% (P < .0001) in empiric and ≥20% (P < .035) in IPT and incident TB by ≥17% (P ≤ .0324) only in IPT. Conclusions: Empiric TB treatment offered no longer-term advantage over IPT in our population with advanced immunosuppression initiating ART. High IPT adherence significantly lowered death and TB incidence through 96 weeks, emphasizing the benefit of ART plus IPT initiation and completion, in persons with advanced HIV living in high TB-burden, resource-limited settings.

Brief Report: No Differences Between Lopinavir/Ritonavir and Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy on Clearance of Plasmodium falciparum Subclinical Parasitemia in Adults Living With HIV Starting Treatment (A5297).

BACKGROUND: HIV protease inhibitors anti-Plasmodium falciparum activity in adults remains uncertain. METHODS: Adults with HIV CD4+ counts >200 cells/mm3 starting antiretroviral therapy (ART) with P. falciparum subclinical parasitemia (Pf SCP) were randomized 1:1 to (step 1) protease inhibitor lopinavir/ritonavir (LPV/r)-based (arm A) or nonnucleoside reverse transcriptase inhibitor (nNRTI)-based ART (arm B) for 15 days. In step 2, participants received nNRTI-based ART and trimethoprim/sulfamethoxazole prophylaxis for 15 days. P. falciparum SCP clearance was measured by polymerase chain reaction. The Fisher exact test [95% exact confidence interval (CI)] was used to compare proportions of P. falciparum SCP clearance (<10 parasites/µL on 3 occasions within 24 hours) between LPV/r and nNRTI arms at day 15. The Kaplan-Meier method and log-rank test were used to compare time-to-clearance. RESULTS: Fifty-two adults from Kenya, Malawi, and Uganda with a median age = 31 (Q1, Q3: 24-39) years, 33% women, with baseline median CD4+ counts of 324 (259-404) cells/mm3, median HIV-1 RNA viremia of 5.18 log10 copies/mL (4.60-5.71), and median estimated P. falciparum density of 454 parasites/µL (83-2219) enrolled in the study. Forty-nine (94%) participants completed the study. At day 15, there was no statistically significant difference in the proportions of P. falciparum SCP clearance between the LPV/r (23.1% clearance; 6 of the 26) and nNRTI (26.9% clearance; 7 of the 26) arms [between-arm difference 3.9% (95% CI, -21.1% to 28.4%; P = 1.00)]. No significant difference in time-to-clearance was observed between the arms (P = 0.80). CONCLUSIONS: In a small randomized study of adults starting ART with P. falciparum SCP, no statistically significant differences were seen between LPV/r- and nNRTI-based ART in P. falciparum SCP clearance after 15 days of treatment.

Urine Lipoarabinomannan Testing in Adults With Advanced Human Immunodeficiency Virus in a Trial of Empiric Tuberculosis Therapy.

BACKGROUND: The urine lipoarabinomannan (LAM) antigen test is a tuberculosis (TB) diagnostic test with highest sensitivity in individuals with advanced human immunodeficiency virus (HIV). Its role in TB diagnostic algorithms for HIV-positive outpatients remains unclear. METHODS: The AIDS Clinical Trials Group (ACTG) A5274 trial demonstrated that empiric TB therapy did not improve 24-week survival compared to isoniazid preventive therapy (IPT) in TB screen-negative HIV-positive adults initiating antiretroviral therapy with CD4 counts <50 cells/µL. Retrospective LAM testing was performed on stored urine obtained at baseline. We determined the proportion of LAM-positive participants and conducted modified intent-to-treat analysis excluding LAM-positive participants to determine the effect on 24-week survival, TB incidence, and time to TB using Kaplan-Meier method. RESULTS: A5274 enrolled 850 participants; 53% were male and the median CD4 count was 18 (interquartile range, 9-32) cells/µL. Of the 850, 566 (67%) had LAM testing (283 per arm); 28 (5%) were positive (21 [7%] and 7 [2%] in the empiric and IPT arms, respectively). Of those LAM-positive, 1 participant in each arm died and 5 of 21 and 0 of 7 in empiric and IPT arms, respectively, developed TB. After excluding these 28 cases, there were 19 and 21 deaths in the empiric and IPT arms, respectively (P = .88). TB incidence remained higher (4.6% vs 2%, P = .04) and time to TB remained faster in the empiric arm (P = .04). CONCLUSIONS: Among outpatients with advanced HIV who screened negative for TB by clinical symptoms, microscopy, and Xpert testing, LAM testing identified an additional 5% of individuals with TB. Positive LAM results did not change mortality or TB incidence.

Integrative Multi-Omics Reveals Serum Markers of Tuberculosis in Advanced HIV.

Tuberculosis (TB) accounts for disproportionate morbidity and mortality among persons living with HIV (PLWH). Conventional methods of TB diagnosis, including smear microscopy and Xpert MTB/RIF, have lower sensitivity in PLWH. Novel high-throughput approaches, such as miRNAomics and metabolomics, may advance our ability to recognize subclinical and difficult-to-diagnose TB, especially in very advanced HIV. We conducted a case-control study leveraging REMEMBER, a multi-country, open-label randomized controlled trial comparing 4-drug empiric standard TB treatment with isoniazid preventive therapy in PLWH initiating antiretroviral therapy (ART) with CD4 cell counts <50 cells/µL. Twenty-three cases of incident TB were site-matched with 32 controls to identify microRNAs (miRNAs), metabolites, and cytokines/chemokines, associated with the development of newly diagnosed TB in PLWH. Differentially expressed miRNA analysis revealed 11 altered miRNAs with a fold change higher than 1.4 or lower than -1.4 in cases relative to controls (p<0.05). Our analysis revealed no differentially abundant metabolites between cases and controls. We found higher TNFα and IP-10/CXCL10 in cases (p=0.011, p=0.0005), and higher MDC/CCL22 in controls (p=0.0072). A decision-tree algorithm identified gamma-glutamylthreonine and hsa-miR-215-5p as the optimal variables to classify incident TB cases (AUC 0.965; 95% CI 0.925-1.000). hsa-miR-215-5p, which targets genes in the TGF-ß signaling pathway, was downregulated in cases. Gamma-glutamylthreonine, a breakdown product of protein catabolism, was less abundant in cases. To our knowledge, this is one of the first uses of a multi-omics approach to identify incident TB in severely immunosuppressed PLWH.

Mentoring upcoming researchers for non-communicable diseases' research and practice in Malawi.

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

Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052.

BACKGROUND: Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. METHODS: Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env). RESULTS: Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. CONCLUSIONS: We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data.

Distal Sensory Peripheral Neuropathy in Human Immunodeficiency Virus Type 1-Positive Individuals Before and After Antiretroviral Therapy Initiation in Diverse Resource-Limited Settings.

BACKGROUND: Distal sensory peripheral neuropathy (DSPN) is a complication of human immunodeficiency virus (HIV). We estimate DSPN prevalence in 7 resource-limited settings (RLSs) for combination antiretroviral therapy (cART)-naive people living with HIV (PLWH) compared with matched participants not living with HIV and in PLWH virally suppressed on 1 of 3 cART regimens. METHODS: PLWH with a CD4+ count <300 cells/mm3 underwent standardized neurological examination and functional status assessments before and every 24 weeks after starting cART. Matched individuals not living with HIV underwent the same examinations once.Associations between covariates with DSPN at entry were assessed using the χ2 test, and virally suppressed PLWH were assessed using generalized estimating equations. RESULTS: Before initiating cART, 21.3% of PLWH had DSPN compared with 8.5% of people not living with HIV (n = 2400; χ2(df = 1) = 96.5; P < .00001). PLWH with DSPN were more likely to report inability to work [χ2(df = 1) = 10.6; P = .001] and depression [χ2(df = 1) = 8.9; P = .003] than PLWH without DSPN. Overall prevalence of DSPN among those virally suppressed on cART decreased: 20.3%, week 48; 15.3%, week 144; and 10.3%, week 192. Incident DSPN was seen in 127 PLWH. Longitudinally, DSPN was more likely in older individuals (P < .001) and PLWH with less education (P = .03). There was no significant association between cART regimen and DSPN. CONCLUSIONS: Although the prevalence of DSPN decreased following cART initiation in PLWH, further research could identify strategies to prevent or ameliorate residual DSPN after initiating cART in RLSs.

Phylogenetic Methods Inconsistently Predict the Direction of HIV Transmission Among Heterosexual Pairs in the HPTN 052 Cohort.

BACKGROUND: We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission. METHODS: For 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees. RESULTS: DoT was predicted correctly for both single-pair and subtype-specific trees in 22 pairs (67%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples. CONCLUSIONS: Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.