Noninfectious Comorbidity in the African Cohort Study.

BACKGROUND: Noninfectious comorbid diseases (NCDs) contribute to morbidity and mortality in human immunodeficiency virus (HIV)-infected populations in resource-rich countries. With antiretroviral therapy (ART) scale-up in Africa, understanding burden NCD informs public health strategy. METHODS: At enrollment, participants at 11 HIV clinics in Kenya, Uganda, Tanzania, and Nigeria underwent medical history, physical, laboratory, and neuropsychological assessments to identify elevated blood pressure, hypercholesterolemia, dysglycemia, renal insufficiency, and cognitive impairment. Poisson regression models estimated adjusted relative risks (ARRs) and 95% confidence intervals (CIs) for the number of NCDs associated with factors of interest. Logistic regression was used to evaluate each NCD separately among HIV-infected participants. RESULTS: Among 2720 participants with complete NCD data, 2159 (79.4%) were HIV-infected. Of those, 1426 (66.0%) were taking ART and 813 (37.7%) had at least 1 NCD. HIV infection was associated with more NCDs, especially with ART (ARR, 1.42; 95% CI, 1.22-1.66). In addition to age, body mass index, and program site, ART usage was associated with more NCDs (ARR, 1.50; 95% CI, 1.27-1.78 for virologically suppressed and ARR, 1.38; 95% CI, 1.13-1.68 for viremic) among HIV-infected participants. In participants taking ART, CD4 nadir below 200 cells/mm3 was associated with more NCDs (ARR, 1.43; 95% CI, 1.06-1.93). ART use was independently associated with hypercholesterolemia and dysglycemia. Program site was significantly associated with all comorbidities except renal insufficiency. CONCLUSIONS: HIV infection was a risk for NCDs, which were common in HIV-infected participants, geographically variable, and largely consistent with metabolic complications of first-line ART.

Use of telemedicine for trauma care since the Russian invasion of Ukraine: A qualitative assessment.

INTRODUCTION: Ukraine's health and trauma system has been detrimentally impacted since the start of the Russian invasion in February 2022. Use of telemedicine became critical to providing timely medical care. As such, the aim of this study was to describe telemedicine's use in the health and trauma system of Ukraine following the full-scale invasion. METHODS: We conducted qualitative key informant interviews with military and civilian health care workers using an expanded version of the Global Trauma System Evaluation Tool which had components focusing on telemedicine use. Thematic content analysis was used to derive key telemedicine themes from interviews. RESULTS: We conducted 36 key informant interviews. Most respondents described using telemedicine through informal means of communication such as messaging apps to meet patient care needs. Concerns and challenges with use of telemedicine included weapons targeting, internet connections and safety of communications from Russian hackers. A unified system for telemedicine would greatly improve use in country both during and post conflict. DISCUSSION: Telemedicine use has rapidly increased in Ukraine during the current conflict particularly in the scope of providing trauma care when numerous specialties are needed. Development of a unified, secure telemedicine system with mechanisms for integrating multinational medical support would aid in providing swift medical care to persons injured in the conflict or unable to access a specialty provider in their proximity.

The Emergence of MOVES SLC Life-Support System Equipment for En-Route Trauma Care in Ukraine During a Qualitative Assessment.

INTRODUCTION: Ukraine's health and trauma system has been detrimentally impacted since the Russian Federation invasion in February 2022. The number and extent of injuries experienced in Ukraine because of trench warfare and high-intensity large-scale combat operations has not been seen in recent conflicts. Understanding attitudes and perceptions around the use of devices and products including MOVES (monitor, oxygen concentrator, ventilator, and suction system) and its use in the large-scale combat operation environment can inform lessons learned for improved prehospital care in Ukraine, as well as in other future conflicts. MATERIAL AND METHODS: We conducted qualitative key informant interviews with military and civilian Ukrainian health care workers during the ongoing conflict using an expanded version of the Global Trauma System Evaluation Tool. We focused the analysis on identifying and understanding the capability of MOVES Micro-integrated Life Support System (SLC). RESULTS: Thirty-six participants were interviewed; 56% were military and 44% were civilians and representative of all NATO roles or levels of care. Sixty-one percent of participants were male. Seventy-two percent of participants were stationed in the Eastern and Northern regions. The mean age was 34.9 years. Sixty-seven percent of care providers reported using MOVES SLC and the remainder stated they wanted the device. The device was sometimes referenced as a "portable ventilator." Of other donated surgical equipment, MOVES SLC was described as "unique." A stabilization modification was suggested as a need given the ad hoc vehicles used for en-route critical care. Participants reacted positively to using MOVES SLC and the capabilities and improvements in care that MOVES SLC can provide for en-route care of critically injured patients. CONCLUSIONS: MOVES SLC is well regarded by Ukrainian trauma care providers. Training may be necessary to increase the quality of care when utilizing these devices, and vehicle modifications may be necessary for use given some concerns over the equipment falling during transport. There is a need to study how this equipment improves the ability of limited medical personnel to provide prolonged care for a larger number of patients with reduced medical resupply.

Resistance to RevM10 inhibition reflects a conformational switch in the HIV-1 Rev response element.

Nuclear export of certain HIV-1 mRNAs requires an interaction between the viral Rev protein and the Rev response element (RRE), a structured element located in the Env region of its RNA genome. This interaction is an attractive target for both drug design and gene therapy, exemplified by RevM10, a transdominant negative protein that, when introduced into host cells, disrupts viral mRNA export. However, two silent G->A mutations in the RRE (RRE61) confer RevM10 resistance, which prompted us to examine RRE structure using a novel chemical probing strategy. Variations in region III/IV/V of mutant RNAs suggest a stepwise rearrangement to RevM10 resistance. Mass spectrometry was used to directly assess Rev "loading" onto RRE and its variants, indicating that this is unaffected by RNA structural changes. Similarity in chemical footprints with mutant protein implicates additional host factors in RevM10 resistance.

Virological Suppression and Patterns of Resistance Amongst Patients on Antiretroviral Therapy at 4 Nigerian Military Hospitals.

BACKGROUND: In resource-constrained settings, plasma HIV-1 RNA quantification has not been routinely available for the monitoring of response to antiretroviral therapy. This study evaluated virological suppression rates amongst patients on first-line ART in four Nigerian military hospitals. METHODS: We conducted a cross-sectional study of 325 randomly selected adult clinic clients (≥18 years old) on first-line ART regimens at four Nigerian military hospitals. Plasma HIV-1 RNA was assayed using a Roche COBAS TaqMan48 with High Pure System. Virological failure was defined as HIV-1 RNA >1000 copies/ml. Specimens with HIV-1 RNA >1000 copies/ml were referred for genotyping. RESULTS: HIV-1 RNA results were obtained in 322 participants. Two hundred and seventy-eight study participants (86.3%) had HIV viral RNA < 1000 copies/ml, including 273 (84.8%) with HIV- 1 RNA <400 copies/ml. HIV drug resistance genotyping results were obtained in 35 of 44 study participants with HIV-1 RNA >1000 copies/ml. Only 14% (5/35) had no resistance mutations. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations (K103N or Y188C). 25% (5/25) of participants failing on Zidovudine had more than two thymidine analogue mutations (TAMs). CONCLUSION: We observed a high virological suppression rate among the study participants. However, a large proportion of virologically unsuppressed clients had identifiable resistance mutations. The study demonstrates that viral load monitoring is feasible at Nigerian military hospitals and supports the current WHO HIV treatment guidelines which emphasize virological monitoring of patients on ART for early detection of treatment failure.

Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings.

BACKGROUND: Screening people living with HIV for hepatitis B virus (HBV) co-infection is recommended in resource-rich settings to optimize HIV antiretroviral therapy (ART) and mitigate HBV-related liver disease. This review examines the need, feasibility, and impact of screening for HBV in resource-limited settings (RLS). METHODS: We searched 6 databases to identify peer-reviewed publications between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub-Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg) rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity, mortality, or liver disease progression; and/or (4) impact of HBV-suppressive antiretroviral medications as part of ART on at least one of 5 outcomes (mortality, morbidity, HIV transmission, retention in HIV care, or quality of life). We rated the quality of individual articles and summarized the body of evidence and expected impact of each intervention per outcome addressed. RESULTS: Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa varied from 0% to >28.4%. RSA performance in RLS showed good, although variable, sensitivity and specificity. Quality of studies ranged from strong to weak. Overall quality of evidence for the impact of HIV/HBV co-infection and ART on morbidity and mortality was fair and good to fair, respectively. CONCLUSIONS: Combined, the body of evidence reviewed suggests that HBsAg screening among people living with HIV could have substantial impact on preventing morbidity and mortality among HIV/HBV co-infected individuals in RLS.

Short communication: east meets west: a description of HIV-1 drug resistance mutation patterns of patients failing first line therapy in PEPFAR clinics from Uganda and Nigeria.

HIV-1 viral load (VL) monitoring is recommended but seldom performed in resource-constrained countries. An evaluation of patients receiving first-line antiretroviral therapy in a multicountry PEPFAR program (RV288) was performed to determine the rates and predictors of virologic suppression. Resistance data from treatment failures are available from Uganda and Nigeria. Each country enrolled 325 subjects into this cross-sectional study. Subjects on first-line therapy were randomly selected for HIV RNA testing (viral load). Regimens included efavirenz or nevirapine with zidovudine/lamivudine or tenofovir/lamivudine. VL was determined from plasma using the Roche COBAS TaqMan HIV-1 Test, High Pure System v1.0 (47 copies/ml). Genotypic resistance testing was performed on samples with VL>1,000 copies/ml. From Uganda, 85% of subjects were undetectable while 7% (23/325) had VL>1,000 copies/ml. The HIV-1 subtype distribution was as follows: A=47.6%, C=14.3%, and D=38.1%. No resistance mutations were found in 14% of subjects. All subjects with resistance had the M184V mutation. Of subjects failing a zidovudine regimen less than 1 year, 88% (7/8) had no thymidine analogue mutations (TAMs), compared to 50% (4/8) failing greater than 1 year. Four subjects (25%) had more than two mutations from the TAM-1 pathway (41L, 210W, 215Y). In Nigeria, 82% were undetectable while 14% (45/325) had VL>1,000 copies/ml. HIV-1 subtype distribution was as follows: 62.8%=CRF02_AG, 34%=pure G, and 2.8%=A. Of the 35 genotyped subjects, 14% (5/35) had no resistance mutations. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations. Forty percent (10/25) of subjects on zidovudine failed without TAMs. Another 25% (5/25) of subjects failing on zidovudine had more than two TAM-1 mutations. Individuals failing first-line antiretroviral therapy (ART) may retain sensitivity to one or more nucleoside analogues from the regimen. Knowledge of drug resistance patterns allow for selection of drugs that can be recycled in future regimens. Accumulation of resistance mutations may compromise future treatment options.

Occurrence of etravirine/rilpivirine-specific resistance mutations selected by efavirenz and nevirapine in Kenyan patients with non-B HIV-1 subtypes failing antiretroviral therapy.

Resistance to efavirenz and nevirapine has not been associated with mutations at position 138 of reverse transcriptase. In an evaluation of virologic suppression rates in PEPFAR (President's Emergency Plan For AIDS Relief) clinics in Kenya among patients on first-line therapy (RV288), 63% (617/975) of randomly selected patients on antiretroviral therapy were suppressed (HIV RNA<400 copies/ml). Among those with non-nucleoside reverse transcriptase inhibitor resistance (n = 101), 14 (13.8%) had substitutions at 138 (A, G, K or Q), mutations selected only by etravirine and rilpivirine in subtype B viruses. All 14 patients received efavirenz or nevirapine, not etravirine or rilpivirine, and were predominantly subtype A1. This may be the first report of efavirenz and nevirapine selecting these mutations in these subtypes.