Phenotypic and genotypic acyclovir resistance surveillance of genital herpes simplex virus 2 in South Africa.

Acyclovir (ACV) is currently included in the syndromic management algorithm for genital ulcer disease in South Africa, and is the recommended first-line treatment for herpes simplex virus 2 (HSV-2). In the majority of cases, HSV-2 resistance to ACV is due to amino acid changes within the viral thymidine kinase (TK). Phenotypic and genotypic ACV resistance surveillance of HSV-2 derived from genital ulcer disease swab specimens was conducted at a primary healthcare facility in Johannesburg between 2018 and 2020. The objectives of this surveillance were to identify ACV resistance-associated mutations and polymorphisms in HSV-2 TK, and to determine the phenotypic ACV resistance profiles of the corresponding clinical HSV-2 isolates. Genotypic analysis of TK from 67 HSV-2 positive genital ulcer swabs revealed 48 specimens with TK mutations, conferring 113 nucleotide changes. No resistance-associated mutations were found, however, we identified nine known natural polymorphisms (R26H, A27T, S29A, G39E, N78D, L140F, T159I, R220K and R284S) and five amino acid changes of unknown significance (R18C, G39K, M70R, P75S and L263P). Phenotypic susceptibility testing of 52 cultivable HSV-2 isolates revealed all to be susceptible to ACV with IC50 values of <2 µg/ml. The five amino acid changes of unknown significance identified by genotypic testing were not correlated to phenotypic ACV resistance, and therefore grouped as natural polymorphisms. We did not detect any unknown or resistance-associated mutations in specimens that could not be phenotypically tested for ACV resistance. Our findings will supplement existing databases of HSV antiviral resistance-associated mutations and polymorphisms that could be used for genotypic ACV resistance screening.

Knowledge of HIV status and antiretroviral therapy use among sexually transmitted infections service attendees and the case for improving the integration of services in South Africa: A cross sectional study.

We describe knowledge of human immunodeficiency virus (HIV) status, correct report of HIV status and antiretroviral therapy (ART) use among sexually transmitted infection (STI) service attendees in South Africa.An anonymous questionnaire was administered and serological HIV testing done. Proportions of attendees reporting knowledge of HIV status and HIV status consistent with laboratory results and ART use (among HIV positives) were determined as were factors associated with knowledge and inconsistent report of HIV status.Of 1054 attendees, 288 (27.3%) were HIV positive and 830 (78.8%) self-reported knowledge of HIV status. Not knowing one's HIV status was associated with male gender [adjusted Odds Ratio (aOR) 2.66 (95% confidence interval (CI) 1.70-4.18] medical circumcision [aOR 0.48 (95% CI 0.24-0.95)] and site [Gauteng Province (GP)-aOR 6.20 (95% CI 3.51-10.95), Eastern Cape (EC)-aOR 17.29 (95% CI 10.08- 29.66) versus Free State (FS)/Western Cape (WC) sites]. Of 219 HIV positive attendees with knowledge of HIV status, 136 (62.1%) self-reported being HIV positive, of whom 80 (58.8%) reported taking ARVs in the preceding 3 days. Inconsistent report of status was associated with males [aOR 2.26 (95%CI 1.05-4.87)], prior STI treatment [aOR 0.33 (95% CI 0.16-0.69)], recent HIV testing (6months) [aOR 3.20 (95% CI 1.62-6.36)] and site [GP-aOR 6.89 (95% 3.21-14.82), EC-aOR 5.08 (95% CI 2.15-11.64) versus FS/WC sites]. Knowledge of HIV status was lower than targeted. HIV testing and linkage to care services are essential in STI-related care and validation of self-reported indicators in this population maybe necessary.

Prevalence and Hospital Management of Amphotericin B Deoxycholate-Related Toxicities during Treatment of HIV-Associated Cryptococcal Meningitis in South Africa.

BACKGROUND: We aimed to establish the prevalence of amphotericin B deoxycholate (AmBd)-related toxicities among South African patients with cryptococcosis and determine adherence to international recommendations to prevent, monitor and manage AmBd-related toxicities. METHODS: Clinical data were collected from cases of laboratory-confirmed cryptococcosis at 25 hospitals, October 2012 -February 2013. Anemia was defined as hemoglobin (Hb) concentration <10 g/dl, hypokalemia as serum potassium (K) <3.4 mEq/L and nephrotoxicity as an increase in serum creatinine (Cr) to >1.1 times the upper limit of normal. To determine adherence to toxicity prevention recommendations, we documented whether baseline Hb, K and Cr tests were performed, whether pre-emptive hydration and IV potassium chloride (KCl) was administered prior to 80% and 60% of AmBd doses and whether daily oral KCl supplementation was given ≥60% of the time. To determine adherence to monitoring recommendations, we ascertained whether a daily fluid chart was completed, Hb was monitored weekly and K or Cr were monitored bi-weekly. RESULTS: Of 846 patients, clinical data were available for 76% (642/846), 82% (524/642) of whom received AmBd. Sixty-four per cent (n = 333) had documented baseline laboratory tests, 40% (n = 211) were given pre-emptive hydration and 14% (n = 72) and 19% (n = 101) received intravenous and oral KCl. While on AmBd, 88% (n = 452) had fluid monitoring; 27% (n = 142), 45% (n = 235) and 44% (n = 232) had Hb, K and Cr levels monitored. Toxicities developed frequently during treatment: anemia, 16% (86/524); hypokalemia, 43% (226/524) and nephrotoxicity, 32% (169/524). CONCLUSION: AmBd-related toxicities occurred frequently but were potentially preventable with adequate monitoring, supplemental fluid and electrolyte therapies.