Challenges encountered by human immunodeficiency virus positive pregnant women on taking antiretrovirals in a public health unit of the Manzini region, Swaziland

In Swaziland, the Ministry of Health adopted the prevention of mother-to-transmission (PMTCT) Option A as a feasible and less costly way to expand the PMTCT services nationwide. Despite major success since the programme started, some barriers, such as the challenge of follow-up care for human immunodeficiency virus (HIV)-positive pregnant mothers still exist. The present study aimed to describe the challenges that HIV-positive pregnant mothers encountered on taking antiretrovirals (ARVs) in a health unit of the Manzini region, Swaziland. A qualitative, exploratory and descriptive research design was used, and data were collected through semi-structured individual interviews and field notes. Purposive sampling was used to select the study site and the population. Permission was requested from the participants to record the interviews. The study population were HIV-positive pregnant mothers, aged between 18 and 40 years, which were enrolled in the PMTCT B+ programme. The PMTCT B+ programme was perceived as preventing the transfer of HIV transmission from mother to child. It boosts the mother's immune system, prevents opportunistic infections and prolongs life. Challenges of taking ARVs emerged as a theme. The participants displayed knowledge and understanding of the programme, yet discrimination and no support from families and partners were mentioned. (Afr J Reprod Health 2022; 26[5]: 41-49).

Predictors of Adherence to Highly Active Antiretroviral Therapy among HIV Patients attending Selected Comprehensive Care Centres in Kericho County, Kenya

Highly Active Antiretroviral Therapy (HAART) is undoubtedly the only proven remedy known to improve the health outcomes and reduce AIDS-related mortality. However, just like other chronic diseases, HIV presents significant challenges in achieving and maintaining adherence to medication. The effectiveness of HAART solely depends on adherence. For maximum medication benefits, a nearperfect adherence levels of >95% is required yet data from different studies indicate that few, if any patients have achieved perfect adherence. The main objective of the study was to the determine predictors of adherence to Highly Active Antiretroviral Therapy among HIV patients attending selected comprehensive care centres in Kericho County. MATERIALS AND METHODS A descriptive cross-sectional study was adopted, involving 280 HIV patients (≥ 15 years) on HAART from three selected Comprehensive Care Centres in Kericho County, Kenya. Quantitative and qualitative data were collected using interviewer administered semi-structured questionnaires and key informant interviews, respectively. Purposive sampling was used to select the three health facilities while systematic sampling was used for participant selection. Adherence was measured using viral load. Data was analyzed using SPSS version 25. Logistic regression analysis was used to determine the association between adherence to HAART and various independent variables. Results were considered to be significant at p < 0.05). RESULTS AND CONCLUSION Seventy six percent (76%) of the respondents had optimal adherence while 24% had sub-optimal adherence. More females than males were on treatment. Use of HAART alternatives was a risk factor for sub-optimal adherence (p=0.011). Having someone/tool to remind of when to take medication and disclosure of HIV positive status to spouse were found to significantly promote adherence to HAART with p=0.034) and p=0.048, respectively. African Journal of Health Sciences Volume 34, Issue No.4, July- August 2021 465 RECOMMENDATIONS Several studies have been done on the socio-demographic and socio-economic factors associated with adherence to HAART. Findings from this study indicate that attitudes and practices towards HAART have significant effects on adherence hence more research should be done on attitudes and practice aspects of adherence

Effect of RelB on HIV-1 Vpr-mediated transcription activation and cell G2/M arrest / 病毒学报

Vpr, an auxiliary protein of HIV-1(Human immunodeficiency virus type 1), exerts important functions to promote viral replication and AIDS progression. In this study, we performed a yeast two-hybrid screening assay using human cDNA library to further investigate the molecular mechanism of various functions of Vpr RelB, a key protein in NF-kappaB signaling pathway, was identified as a Vpr interaction protein by co-immunoprecipitation. Further investigations indicated that RelB not only promoted the Vpr-mediated activation of NF-kappaB reporter gene, but also enhanced the transactivation of HIV LTR. Moreover, the results showed that RelB promoted Vpr-induced cell cycle G2/M arrest. Collectively, these results indicated that RelB might interact with Vpr and regulate its transcriptional activation and cell cycle arrest.

Genetic architecture of HIV-1 genes circulating in north India & their functional implications.

This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Mynmar with 3 copies of Nfκb sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted.

Design, synthesis and evaluation of novel 2H-1, 4-benzodiazepine-2-ones as inhibitors of HIV-1 transcription / 药学学报

HIV-1 trans-activator of transcription (Tat) plays a critical role in HIV-1 transcription. Based on the beta-turn motif present in HIV-1 Tat, a series of novel benzodiazepine analogs were designed as beta-turn mimetics and prepared from p-chloro-nitrobenzene/2-phenylacetonitrile, p-toluidine/benzoyl chloride, or (Z)-7-nitro-5-phenyl-1H-benzo[e][1, 4]diazepin-2(3H)-one (nitrazepam) through different synthetic routes. Preliminary biological evaluation indicated that compound 30 exhibited inhibitory activity on HIV-1 tat-mediated LTR transcription with EC50 of 25.0 micromol x L(-1) and showed no obvious cytotoxic effects on TZM-BI cells under the concentration of 100 micromol x L(-1).

Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of proteins linking chemokines and TM4SF. Different members exhibit diverse biological functions. In this study, the effect of intracellular CMTM2 on regulating human immunodeficiency virus type-1 (HIV-1) transcription was evaluated.</p><p><b>METHODS</b>The effects of CMTM2 on regulating full-length HIV-1 provirus and the HIV-1 long terminal repeat (LTR)-directed transcription were assessed by luciferase assay. Transcription factor assays, using the luciferase reporter plasmids of AP-1, CRE, and NF-κB were conducted to explore the signaling pathway(s) that may be regulated by CMTM2. The potential relationship between CMTM2 and the transcription factor AP-1 was further analyzed by Western blotting analyses to investigate the effect of CMTM2 on PMA-induced ERK1/2 phosphorylation.</p><p><b>RESULTS</b>The results from the current study revealed that CMTM2 acts as a negative regulator of HIV-1 transcription. CMTM2 exerted a suppressive action on both full-length HIV-1 provirus and HIV-1 LTR-directed transcription. Transcription factor assays showed that CMTM2 selectively inhibited basal AP-1 and CREB activity. Co-expression of HIV-1 Tat, a potent AP-1 and CREB activator, can not reverse CMTM2-mediated AP-1 and CREB inhibition, suggesting a potent and specific effect of CMTM2 on negatively regulating these two signaling pathways.</p><p><b>CONCLUSION</b>Intracellular CMTM2 can negatively regulate HIV-1 transcription, at least in part, by targeting the AP-1 and CREB pathways. Exploring the mechanisms further may lead to new ways to control HIV-1 replication.</p>

Recent progress in the study of HIV-1 transcription factor NF-kappaB and its inhibitors / 药学学报

Human immunodeficiency virus type 1 (HIV-1) transcription is a crucial step in the viral replication cycle, which is considered to be a potential target for inhibition of HIV-1 replication. Among the factors involved in this step, the cellular protein nuclear factor NF-kappaB is the most powerful inducer of HIV-1 transcription. HIV-1 transcription is initiated by the binding of NF-kappaB to the enhancer region in the long terminal repeat (LTR) of HIV-1. Several compounds suppress HIV-1 transcription through the inhibition of NF-kappaB activation. The mechanisms of NF-kappaB in the transcription of HIV-1 and progress of the current inhibitors of NF-kappaB are reviewed.

Genetic characterization of three CRF01_AE full-length HIV type 1 sequences from Fujian Province, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>One of the major characteristics of the human immunodeficiency virus type 1 (HIV-1) is its unusually high degree of genetic variability, which involves in genetic diagnosis, subtyping, vaccine design, and epidemiology. HIV-1 CRF01_AE is a main prevalent HIV-1 recombinant strain in China. In this study, three full-length CRF01_AE genomes from Fujian Province, China were cloned, sequenced, and analyzed; and the further genetic diversity defining and epidemiologic analysis were carried out.</p><p><b>METHODS</b>Proviral DNA was extracted from non-cultured peripheral blood mononuclear cells, the near full-length HIV-1 genome was amplified and the PCR products were cloned into pCR-XL-TOPO vector and sequenced. 5'-long terminal repeat (LTR) and 3'-LTRs were amplified by additional independent PCR and cloned into pMD18T vector. Gene-based phylogenic tree was constructed and genetic distances were calculated by MEGA 3.1. Simplot was used for Bootscan analysis.</p><p><b>RESULTS</b>The phylogeny and genetic distance analysis of the three near full-length sequences confirmed that these three samples clustered with CRF01_AE isolates, more close to Thailand CRF01_AE strain CM240, and were distantly related to African CRF01_AE strain 90CF402. Analysis of their genomic organization revealed the presence of nine potential open reading frames. There were no major deletions, rearrangements, or insertions in the three sequences, but an in-frame stop codon was found in tat gene of Fj051. LTRs of the three sequences contained a few nucleotides mutation. We did not find new mosaic recombinant in the three sequences. The V3 motif was GPGQ in all the three sequences, and there were only few amino acids differences in all three V3 loop sequences.</p><p><b>CONCLUSION</b>This report reveals the background of the three full-length CRF01_AE genomes, the most dominantly circulating HIV-1 strain in Fujian Province, China. The work is essential for the design and development of an effective AIDS vaccine for the region.</p>

Marcadores virologicos no convencionales en pacientes infectados con el virus de la inmunodeficiencia humana: ADN HIV-T, ADN HIV-2LTR y ARN de HIV / Non conventional virological markers in HIV-infected patients: T-HIV DNA, 2LTR-HIV DNA and HIV RNA

La terapia antirretrovial de alta eficacia (TAAE) induce una reducción marcada y persisatente de la viremia plasmática, contribuvendo a disminuir la mortalidad de los pacientes HIV-positivos. Así, la carga viral (CV) es el método de referencia para evaluar la eficacia terapéutica. Sin embargo, aun en presencia de una TAAE eficiente no se ha logrado la erradicación viral. En este estudio analizamos la presencia del ADN total de HIV (ADN HIV-T), del ADN no integrado con 2LTR (ADN HIV-2LTR) y del ARN de HIV, en un grupo de 55 pacientes HIV-positivos en distintos estadios clínicos, con y sin TAAE, mediante ensayos de PCR con revelado colorimétrico en microplaca, optimizados en nuestro laboratorio. La sensibilidad clínica de ARN del HIV fue evaluada con el bDNA, resultando del 74% y del 64%, respectivamente, con una concordancia del 85%. Este ensayo podría utilizado en el seguimiento de pacientes bajo TAAE. EI ADN HIV-2LTR resultó positivo en el 54% aunque estuvo ausente en pacientes con elevada CV. Este marcador se considereba un producto lábil y su presencia se asociaba a infección reciente. Sin embargo, actuales evidencias ponen en discusión su estabilidad por lo que su significado clínico debe ser reconsiderado. La ausencia del ADN HIV-2LTR en pacientes con CV detectable puede relacionarse con la heterogeneidade de la secuencia utilizada para su detección. EI ADN HIV-T estuvo presente en el 100% de las muestras y resultaría relevante como marcador de remisión cuando se dispongan de terapias que efectivamente erradiquen la infección.

A Human Immunodeficiency Virus Type 1 (HIV-1) Tat Cofactor Absent in Rodent Cells is a TAR-associated Factor

BACKGROUND: Although Tat plays a role as a potent transactivator in the viral gene expression from the Human Immunodeficiency Virus type 1 long terminal repeat (HIV-1 LTR), it does not function efficiently in rodent cells implying the absence of a human specific factor essential for Tat-medicated transactivation in rodent cells. In previous experiments, we demonstrated that one of chimeric forms of TAR (transacting responsive element) of HIV-1 LTR compensated the restriction in rodent cells. METHODS: To characterize the nature of the compensation, we tested the effects of several upstream binding factors of HIV-1 LTR by simple substitution, and also examined the role of the configuration of the upstream binding factor(s) indirectly by constructing spacing mutants that contained insertions between Sp1 and TATA box on Tat-mediated transactivation. RESULTS: Human Sp1 had no effect whereas its associated factors displayed differential effects in human and rodent cells. In addition, none of the spacing mutants tested overcame the restriction in rodent cells. Rather, when the secondary structure of the chimeric HIV-1 TAR construct was destroyed, the compensation in rodent cells was disappeared. Interestingly, the proper interaction between Sp1 and TATA box binding proteins, which is essential for Tat-dependent transcription, was dispensable in rodent cells. CONCLUSION: This result suggests that the human-specific Tat cofactor acts to allow Tat to interact effectively in a ribonucleoprotein complex that includes Tat, cellular factors, and TAR RNA, rather than be associated with the HIV-1 LTR upstream DNA binding factors.

A Human Immunodeficiency Virus Type 1 (HIV-1) Tat Cofactor Absent in Rodent Cells is a TAR-associated Factor

BACKGROUND: Although Tat plays a role as a potent transactivator in the viral gene expression from the Human Immunodeficiency Virus type 1 long terminal repeat (HIV-1 LTR), it does not function efficiently in rodent cells implying the absence of a human specific factor essential for Tat-medicated transactivation in rodent cells. In previous experiments, we demonstrated that one of chimeric forms of TAR (transacting responsive element) of HIV-1 LTR compensated the restriction in rodent cells. METHODS: To characterize the nature of the compensation, we tested the effects of several upstream binding factors of HIV-1 LTR by simple substitution, and also examined the role of the configuration of the upstream binding factor(s) indirectly by constructing spacing mutants that contained insertions between Sp1 and TATA box on Tat-mediated transactivation. RESULTS: Human Sp1 had no effect whereas its associated factors displayed differential effects in human and rodent cells. In addition, none of the spacing mutants tested overcame the restriction in rodent cells. Rather, when the secondary structure of the chimeric HIV-1 TAR construct was destroyed, the compensation in rodent cells was disappeared. Interestingly, the proper interaction between Sp1 and TATA box binding proteins, which is essential for Tat-dependent transcription, was dispensable in rodent cells. CONCLUSION: This result suggests that the human-specific Tat cofactor acts to allow Tat to interact effectively in a ribonucleoprotein complex that includes Tat, cellular factors, and TAR RNA, rather than be associated with the HIV-1 LTR upstream DNA binding factors.

Comportamiento clínico-radiológico de la tuberculosis pulmonar en pacientes VIH sero psoitivos y VIH sero negativos / clinical-radiological behavior of pulmonary tuberculosis in HIV-infected patients and non HIV-infected patients

Entre 1990 y 1995 en el Hospital Nacional Dos de Mayo se estudió en forma prospectiva las diferencias clínico-radiológicas de la tuberculosis pulmonar en pacientes infectados por el Virus de Inmunodeficiencia Humana (VIH) y en pacientes VIH sero negativos. Se revisaron 30 casos que cumplieron los criterios de diagnóstico de VHI más TBC pulmonar y un grupo control de 30 pacientes sero negativos que tuvieron sólo el diagnóstico de TBC pulmonar. El análisis de datos se realizó con el método estadístico de cuadro con ajuste de Mantel Haenszel y correcciones de Yates. Se encontraron diferencias significativas entre los grupos de pacientes VHI sero positivos y los sero negativos homosexuales (43 por ciento vs. 0 por ciento, p mayor 0.001); TBC pulmonar asociada a localización extrapulmonar (13 por ciento vs. 4 por ciento; p menor 0.0008), siendo la TBC pleural la asociación más frecuente (63 por ciento); adenopatía mediastinal y/o hiliar (43 por ciento vs. 0 por ciento, p menor 0.003); y un cuadro clínico severo caracterizado por dificultad respiratoria (24 por ciento vs. 5 por ciento p menor 0.01). Se concluye que en pacientes VIH sero positivos, la adenopatía mediastinal y/o hiliar, un cuadro clínico atípico y severo, así como la localización extrapulmonar son los hallazgos más frecuentes. En cambio, los pacientes VIH sero positivos presentan un cuadro clínico más típico (con hemoptisis) y con cavitación.

Cryptosporidium sp. E isospora belli en pacientes con diarrea, infectados por el virus de inmunodeficiencia humana, Maracaibo 1993 / Cryptosporidium sp and isospora belli in patients with diarrhea infected with human immunodeficiency virus. Maracaibo 1993

Para investigar la prevalencia de Cryptosporidium sp e isospora belli entre pacientes con infección por el Virus de Inmunodeficiencia Humana (VIH) y diarrea, se estudiaron 20 pacientes VIH seropositivos con evacuaciones líquidas o semilíquidas, en números de 3 ó más por día, con 7 ó más días de evolución. A cada uno se le practicó examen de heces al fresco y con la coloración de Zielh Neelsen (ZN) modificada, realizándose estos examenes en forma seriada según los resultados, e individualizando cada caso para la solicitud de otros estudios. De los 20 pacientes, la mayoría fueron del sexo masculino y de 25 a 44 años de edad, de ellos 11 (55.5 por ciento) presentaron coccidios asociados a la diarrea. Entre los pacientes con coccidios, 8 presentaron Cryptosporidium sp y a 3 se les encontró Isospora belli correspondiéndole el 40 por ciento y 15 por ciento respectivamente del total. La observación del primer examen de heces al fresco y/o con la tinción de ZN modificada, permitió el diagnóstico en 7 de los pacientes con Cryptosporidium sp y en 2 de los 3 con Isospora belli. En algunos de los casos, Criptosporidiosis (75 por ciento) e Isosporiasis (100 por ciento) fueron la primera infección oportunista. Condiciones sanitarias inadecuadas parecen ser un factor de riesgo importante

Detección de marcadores serológicos del virus de la hepatitis B y del virus de la inmunodeficiencia humana en pacientes drogadictos de Lima / Detection of markers serological of hepatitis B(VHB) of the human inmunodeficiency virus (HIV), in patients addicts in Lima

Este estudio prospectivo se realizó en 100 pacientes drogadictos que son atendidos en una institución no gubernamental de la ciudad de Lima. El objetivo fue detectar la infección por el virus de la Hepatitis B (VHB) y el virus de la inmunodeficiencia humana (VIH), en estos casos, y evaluar los posibles medios de transmisión. Más aún, tratándose de drogadictos no usuarios de drogas endovenosas; factor de conocido riesgo para estas infecciones. Las muestras de sangre, fueron procesadas con la técnica de ELISA, para detectar el HBsAg y Anti-HBc (Hepatitis B) y el Anti-HVI. Los resultados fueron: un caso positivo del HBsAg (1 por ciento), 4 casos del Anti-HBc (4 por ciento), y 2 (2 por ciento) del Anti-VIH. El 68.6 por ciento de los casos, referían haber tenido relaciones sexuales con personas diferentes, 33.7 por ciento con homosexuales, y el 23.2 por ciento con personas de igual sexo para obtener dinero para la droga. La positividad de los marcadores serológicos del VHB, no fue de la magnitud, para ser incluidos como grupos de riesgo; como sí se demostró en un estudio anterior. Aunque existiría cierta relatividad en estos conceptos. Sin embargo, la positividad del VIH, de 2+/100, comparado con las cifras de donantes de sangre de Lima (1+/1,000), sí constituye un importante grupo de riesgo para esta infección, asociada al SIDA. De acuerdo a la información recogida en este estudio, la promiscuidad sexual sería el factor más evidente de trasmisión, en estos drogadictos no usuarios de sustancias inyectables. El VHB y el VIH, se transmiten por esta misma vía, y llegan a causar graves enfermedades crónicas y de mal pronóstico, y por ello es conveniente continuar otras investigaciones similares; y establecer las medidas de control y prevención, para evitar su propagación a contactos, familiares y comunidad en general