Analysis of HIV quasispecies and virological outcome of an HIV D+/R+ kidney–liver transplantation

Introduction Transplantation among HIV positive patients may be a valuable therapeutic intervention. This study involves an HIV D+/R+ kidney–liver transplantation, where PBMC-associated HIV quasispecies were analyzed in donor and transplant recipients (TR) prior to transplantation and thereafter, together with standard viral monitoring. Methods The donor was a 54 year of age HIV infected woman: kidney and liver recipients were two HIV infected men, aged 49 and 61. HIV quasispecies in PBMC was analyzed by ultra-deep sequencing of V3 env region. During TR follow-up, plasma HIV-1 RNA, HIV-1 DNA in PBMC, analysis of proviral integration sites and drug-resistance genotyping were performed. Other virological and immunological monitoring included CMV and EBV DNA quantification in blood and CD4 T cell counts. Results Donor and TR were all ART-HIV suppressed at transplantation. Thereafter, TR maintained a nearly suppressed HIV-1 viremia, but HIV-1 RNA blips and the increase of proviral integration sites in PBMC attested some residual HIV replication. A transient peak in HIV-1 DNA occurred in the liver recipient. No major changes of drug-resistance genotype were detected after transplantation. CMV and EBV transient reactivations were observed only in the kidney recipient, but did not require specific treatment. CD4 counts remained stable. No intermixed quasispecies between donor and TR was observed at transplantation or thereafter. Despite signs of viral evolution in TR, HIV genetic heterogeneity did not increase over the course of the months of follow up. Conclusions No evidence of HIV superinfection was observed in the donor nor in the recipients. The immunosuppressive treatment administrated to TR did not result in clinical relevant viral reactivations.

Case Report: Intravenous Pentamidine Rescue Treatment for Active Chronic Visceral Leishmaniasis in an HIV-1 Infected Patient

The management of visceral leishmaniasis (VL) in HIV-infected patients is complex because of high mortality rates, toxic drug-related side effects, and a high risk of treatment failure and relapse. We report a case of active chronic VL in an HIV-1-infected woman presenting multiple secondary VL episodes over 7 years leading to massive splenomegaly and blood transfusion–dependent anemia despite several treatment courses and secondary prophylaxis. The patient was finally successfully treated with rescue treatment based on intravenous pentamidine. One year after discontinuation of pentamidine the patient presented complete clinical and parasitological response. In patients with active chronic VL, rescue treatment with intravenous pentamidine can be effective and should be considered as rescue treatment.

Neurological deterioration in a patient with HIV-associated cryptococcal meningitis initially improving on antifungal treatment: a case report of coincidental racemose neurocysticercosis

Background Managing HIV-associated cryptococcal meningitis (CM) can become challenging in the presence of concurrent unusual central nervous system infections. Case presentation A 58-year old HIV infected woman new ART starter, who was being treated effectively for cryptococcal meningitis, represented with worsening of neurological symptoms. Brain MRI revealed a multicystic lesion in the left temporal lobe. Anti-fungal treatment was escalated for a suspected cryptococcoma, but post-mortem CSF serological test confirmed racemose neurocysticercosis. Conclusion Patients with HIV-associated CM are highly immunocompromised and may have multiple pathologies simultaneously. In endemic countries, neurocysticercosis should be considered in the differential diagnosis where there is central nervous system deterioration despite effective therapy for CM.

Human and Animal Dirofilariasis in Southeast of France

Dirofilariasis is one of the oldest known zoonotic infections of humans mainly caused by the filarial parasites of the species Dirofilaria immitis and Dirofilaria repens, which primarily infect dogs. A five-year survey (2017 to 2021) was conducted among the dog population to assess the molecular prevalence of Dirofilaria spp. in southeast France. Morphological and genetic analysis were performed on filaroids from dogs and one infected woman from the studied area. A total of 12 (13%) dogs scored molecularly positive for Dirofilaria spp. of which nine carried blood microfilariae. Ocular dirofilariasis was detected in a 79-year-old woman with no travel history. Both electron microscopy and molecular sequencing identified the worm in the human case as D. repens. Molecularly, D. repens isolates were identical in the human and dog cases, representing the only genotype reported so far in France. Despite the distribution of this genotype through all Europe, it was grouped separately with the other two European genotypes and with Asian ones. As in almost all previous human cases in France, D. repens parasites were mainly recovered from the ocular region of patients and were geographically concentrated in the southeastern regions. Data demonstrate the sympatric occurrence of D. immitis and D. repens with high risk of infection to human and dog populations in these investigated geographical areas, thereby underlining the urgent need to implement preventive chemoprophylactic strategies and vector control to reduce the risk of these filaroids in dog and human populations.

Assessing the effectiveness of prevention of mother-to-child HIV transmission

Aim. To analyze the outcomes of a set of interventions to prevent vertical transmission of the human immunodeficiency virus (HIV) in the Republic of Mari El. Methods. A retrospective analysis of temporary registration forms Notifications of the termination of pregnancy in an HIV-infected woman and Notifications of a newborn born by an HIV-infected mother, case histories and outpatient medical records of HIV-infected women who gave birth in 20002018 was carried out. The study included all children born in the Republic of Mari El to HIV-positive women registered with the Republican Center for the Prevention and Control of AIDS and Infectious Diseases, as well as children whose HIV status is detected after birth as a result of epidemiological investigations. The assessment of the risks of transmission as an outcome of the three-step preventive interventions has been carried out. A comparative analysis of the results of perinatal prevention of HIV transmission in the Republic of Mari El and other regions of the Russian Federation was performed. Results. A total of 299 HIV-infected pregnant women and 368 children born to these women during the study period were registered in the region; 63 (21.7%) of these women had more than one child. Over the entire study period, 18 (4.8%) children with confirmed HIV infection were registered. The most common factor associated with infant HIV infection is late maternal HIV diagnosis: (1) several years after childbirth in the absence of antiretroviral (ARV) prophylaxis and the infants were breastfeeding (11 cases, 64.7%); (2) during or shortly after childbirth, when the patient did not receive entire three-step antiretroviral prophylaxis during pregnancy and childbirth (6 cases, 29.4%); (3) in the third trimester of pregnancy (1 case, 5.5%). An important limitation for the successful prevention of vertical transmission of HIV was the lack of routine HIV testing, which is required by women and their partners before and at various stages during pregnancy. A single case of self-infection indicates the need to introduce preventive measures from early adolescence among children. Conclusion. Due to the late maternal HIV diagnosis, during or after delivery, HIV transmission events occurred either with limited or no limited antiretroviral prophylaxis.

High Levels of Within-Host Variations of Human Papillomavirus 16 E1/E2 Genes in Invasive Cervical Cancer

Human papillomavirus type 16 (HPV16) is the most common HPV genotype found in invasive cervical cancer (ICC). Recent comprehensive genomics studies of HPV16 have revealed that a large number of minor nucleotide variations in the viral genome are present in each infected woman; however, it remains unclear whether such within-host variations of HPV16 are linked to cervical carcinogenesis. Here, by employing next-generation sequencing approaches, we explored the mutational profiles of the HPV16 genome within individual clinical specimens from ICC (n = 31) and normal cervix (n = 21) in greater detail. A total of 367 minor nucleotide variations (167 from ICC and 200 from the normal cervix) were detected throughout the viral genome in both groups, while nucleotide variations at high frequencies (>10% abundance in relative read counts in a single sample) were more prevalent in ICC (10 in ICC versus 1 in normal). Among the high-level variations found in ICC, six were located in the E1/E2 genes, and all of them were non-synonymous substitutions (Q142K, M207I, and L262V for E1; D153Y, R302T, and T357A for E2). In vitro functional analyses of these E1/E2 variants revealed that E1/M207I, E2/D153Y, and E2/R302T had reduced abilities to support viral replication, and that E2/D153Y and E2/R302T failed to suppress the viral early promoter. These results imply that some within-host variations of E1/E2 present at high levels in ICC may be positively selected for and contribute to cervical cancer development through dysfunction or de-stabilization of viral replication/transcription proteins.

Contraception Choice among HIV-Positive Women Utilizing Family Planning Services Integrated with HIV Care at the Antiretroviral Therapy Clinic of Jos University Teaching Hospital, Nigeria

Transmission of Human Immunodeficiency Virus from a pregnant HIV-infected woman to her unborn child is one of the ways through which new HIV infections can be acquired. Utilization of contraceptives among HIV-positive women can prevent unintended pregnancies, and the use of dual methods reduces the risk of transmission of sexually transmitted infections including HIV, hence the need to support contraception in them. This study sought to describe the various choices of contraception used by women accessing family planning services integrated with the antiretroviral therapy facility of Jos University Teaching Hospital. In a retrospective study, relevant information was extracted from the records of all women who had sought contraception in the Family Planning unit of the facility from 1st March 2019 – 29th February 2020. The data obtained was analysed using EPI info 7 statistical software. Results: A total of 137 records were reviewed. The most frequent choice of contraception was hormonal implants (61.3%), while the least frequent choice was using condoms alone (1.5%). Less than half (46.7%) of them used dual contraception. Secondary and tertiary educational status, as well as disclosure of HIV-positive status to partner were significantly associated with utilization of dual contraceptive methods (P value =0.0010 and 0.0245 respectively; Odds ratio =5.8199 and 4.3307 respectively). Conclusion: Integration of family planning services with HIV care as a strategy for the prevention of unintended pregnancy is promoted in this facility but there is need to improve the uptake particularly of dual method of contraception. There is also need for inclusion of IUCD in the choices of contraception offered as this method is highly effective, long lasting and has been proven to be safe in well selected HIV patients. Furthermore, screening the clients to identify unmet needs and implementing strategies to meet those needs would enhance the impact of family planning.