Hydroxychloroquine to prevent SARS-CoV-2 infection among healthcare workers: early termination of a phase 3, randomised, open-label, controlled clinical trial.

OBJECTIVE: To assess the effectiveness and safety of hydroxychloroquine (HCQ) prophylaxis for the prevention of SARS-CoV-2 infection in healthcare workers (HCW) on duty during the COVID-19 pandemic. RESULTS: A total of 68 HCWs met the eligibility criteria were randomly allocated to receive HCQ (n = 36) or not (n = 32). There were no significant differences between groups in respects to age, gender, or medical history. Eight participants met the primary efficacy endpoint of SAR-CoV-2 infection during the study period; there was no difference in incidence of SARS-CoV-2 infections between both study arms (HCQ: 5 vs Control: 3, p = 0.538). The relative risk of SARS-CoV-2 infection in the HCQ arm was 1.69 compared to the control group (95%CI 0.41-7.11, p = 0.463); due to poor participant accrual, the resulting statistical power of the primary efficacy outcome was 11.54%. No serious adverse events occurred; however, two (2/36, 5.6%) participants no longer wished to participate in the study and withdrew consent due to recurring grade 1 and 2 adverse events. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04414241. (Registered on June 4, 2020).

Epidemiologic characteristics and clinical features of patients with monkeypox virus infection from a hospital in Peru between July and September 2022.

OBJECTIVES: Monkeypox (Mpox) recent outbreak has changed in terms of predominant transmission route and typical presentation. Describing current epidemiological and clinical characteristics is crucial to identifying cases and halting transmission. METHODS: An observational study was conducted at a Peruvian tertiary-level hospital and included all individuals with Mpox virus infection between July 01 and September 03, 2022. RESULTS: Among 205 confirmed cases, 99% (202/205) were men, 94% (192/205) were men who have sex with men or bisexual, and 66% (136/205) were living with HIV. Regarding sexual behavior, 87% (179/205) had a sexual encounter 21 days before consultation, although only 8% (17/205) identified sexual contact with a Mpox confirmed case; 65% (133/205) had sexual intercourse with casual partners, 55% (112/205) reported a last sexual partner unknown, and 21.5% (44/205) continued having sexual intercourse with symptoms. Systemic symptoms were fever (162/205, 79%), malaise (123/205, 60%), headache (119/205, 58%), fatigue (105/205, 52%), and lymphadenopathy (111/205, 54%). The distribution of skin lesions was generalized (166/205, 81%), located in the anogenital area (160/205, 78%), polymorphic (174/205, 85%), and it was the first symptom identified in 46% (94/205) of cases. Overall, 10% (21/205) required hospitalization, of whom 85.7% (18/205) have HIV infection. Complications included bacterial superinfection (n = 18), proctitis (n = 6), balanitis (n = 4), and necrosis of skin lesions (n = 3). CONCLUSION: In 2022, Mpox mainly affects men who have sex with men and People living with HIV/AIDS. It presents with skin lesions localized to the anogenital area and can lead to severe complications requiring hospitalization.

Comparison of the Virological Response According to the Antiretroviral Regimens in Peruvian HIV Patients Who Presented the M184V Mutation in Two National Hospitals During the Years 2008 to 2019.

Introduction: In patients with HIV in antiretroviral treatment (ART) and virological failure to the first-line regimen, establishing a therapeutic regimen after having identified the M184V mutation, which confers ART resistance, represents a dilemma. Objective: To compare the virological response of the therapeutic regimens prescribed to patients with HIV who presented the M184V mutation in two national hospitals in Lima, Peru, during the years 2008 to 2019, and to determine the risk factors associated with poor virological response. Methods: A retrospective cohort study was developed based on the information of the HIV program participants with the M184V mutation. Results: A total of 175 participants were eligible for the study. The male sex predominated (75.4%), the current median age was 41 years [interquartile range (IQR) 35.84-47.47], and the time on ART was 89 months (IQR 57.7-124.53). The median initial viral load (VL) was 4.5 log10 copies/mL (IQR 3.97-5.09) and the time between genotyping and the change of therapy was 2 months (IQR 0-3.56). The most used antiretroviral regimen was protease inhibitor plus two nucleoside reverse transcriptase inhibitors (55.4%). With the protease inhibitor plus integrase inhibitor (PI + INI) ART, 69% less risk of poor virological response was obtained [p = .019 (confidence interval 95% 0.117-0.825)]. Conclusions: In patients with HIV and the M184V mutation, the PI + INI ART has shown a greater decrease in control VL and, thus, a good virological response. The risk factors associated with a poor virological response were the delay between genotyping and change of therapy, high levels of initial VL, and poor adherence among the participants.

Letter to the editors regarding the paper: Prognostic factors in HIV-positive patients with non-Hodgkin lymphoma: a Peruvian experience.

Non-Hodgkin Lymphoma (NHL) is a neoplasm associated with a group of malignancies called AIDs-Defining Malignancies (ADMs) in Human-Immunodeficiency Virus (HIV) -patients. Similar to the case of NHL in Latin America, particularly in Peru, the amount of research done on others ADMs is limited, especially in the case of Kaposi's Sarcoma (KS). Prior investigations have talked about the great potential risk that represents this illness in latin american population, but topics as prognosis factors are yet to be well defined. In this letter, we address the importance of investigation in this area and include previously reported data that may enlighten the current national standpoint.

The HLA-C*04: 01/KIR2DS4 gene combination and human leukocyte antigen alleles with high population frequency drive rate of HIV disease progression.

OBJECTIVE: The objective of this study is to identify human leukocyte antigen (HLA) class I and killer-cell immunoglobulin-like receptor (KIR) genotypes associated with different risks for HIV acquisition and HIV disease progression. DESIGN: A cross-sectional study of a cohort of 468 high-risk individuals (246 HIV-positive and 222 HIV-negative) from outpatient clinics in Lima (Perú). METHODS: The cohort was high-resolution HLA and KIR-typed and analysed for potential differences in single-allele frequencies and allele combinations between HIV-positive and HIV-negative individuals and for associations with HIV viral load and CD4 cell counts in infected individuals. RESULTS: HLA class I alleles associated with a lack of viral control had a significantly higher population frequency than relatively protective alleles (P = 0.0093), in line with a rare allele advantage. HLA-A02 : 01 and HLA-C04 : 01 were both associated with high viral loads (P = 0.0313 and 0.0001, respectively) and low CD4 cell counts (P = 0.0008 and 0.0087, respectively). Importantly, the association between HLA-C04 : 01 and poor viral control was not due to its linkage disequilibrium with other HLA alleles. Rather, the coexpression of its putative KIR ligand KIR2DS4f was critically linked to elevated viral loads. CONCLUSION: These results highlight the impact of population allele frequency on viral control and identify a novel association between HLA-C04 : 01 in combination with KIR2DS4f and uncontrolled HIV infection. Our data further support the importance of the interplay of markers of the adaptive and innate immune system in viral control.

Lack of evidence of hepatitis C and HIV co-infection among men who have sex with men in Peru.

Hepatitis C virus (HCV) infection occurs among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) because of shared routes of transmission. To assess the association between HCV and HIV infection among MSM in Peru, we conducted a matched case-control study (162 HIV-positive cases and 324 HIV-negative controls) among participants of an HIV sentinel surveillance survey in six urban cities. The HCV infection was initially screened using anti-HCV ELISA and immunoblot assay, and thereafter confirmed by the HCV RNA qualitative assay. Among cases, no confirmed HCV infection was found while among controls, only two confirmed HCV infections were reported (0.62%). This matched case-control reports a very low probability of association between HCV and HIV co-infection and suggests a very low prevalence of HCV infection among MSM in Peru.

High HIV and ulcerative sexually transmitted infection incidence estimates among men who have sex with men in Peru: awaiting for an effective preventive intervention.

BACKGROUND: In the Andean Region, HIV and sexually transmitted infections (STI) are most prevalent among men who have sex with men (MSM), but incidence estimates and associated factors have never been prospectively assessed. METHODS: A cohort of 1,056 high-risk HIV-negative MSM in Lima, Peru, were recruited during 1998-2000 (the ALASKA Cohort), and a nested case-control analysis was conducted between seroconverters and nonseroconverters, matched 1:3 by age and duration of follow-up for comparison of risk behaviors, acute retroviral symptoms, circumcision, and STI. RESULTS: During average follow-up of 335 days, 34 men seroconverted, providing a HIV incidence estimate of 3.5 per 100 person-years [95% confidence interval (CI): 2.3 to 4.7]. High syphilis (8.4 per 100 person-years, 95% CI: 6.7 to 10.1) and herpes simplex virus type 2 (HSV-2) infection (10.4 per 100 person-years, 95% CI: 8.6 to 11.9) incidence estimates were obtained. HIV seroconverters were more likely than men who remained seronegative to report fever >or=3 days (46% vs. 7%), to seek medical care (62% vs. 27%), and to have >or=1 casual partner (86.2% vs. 74.1%) since their last visit. HIV seroconverters also were more likely to have acquired syphilis or HSV-2 infection (31% vs. 8% among initially HSV-2-seronegative men) although they were less likely to be circumcised (4.2% vs. 20.6%, a nonsignificant difference). In multivariate analysis, incident syphilis or HSV-2 infection (odds ratio [OR]: 5.9, 95% CI: 1.5 to 22.7) and sex with any casual partner (OR: 4.8, 95% CI: 0.9 to 26.2) were associated with HIV seroconversion. CONCLUSIONS: STI that may cause anogenital ulcers are important risk factors for HIV acquisition among high-risk MSM in Lima, a population with a very high HIV incidence estimate. Synergistic interventions focusing in preventing both HIV and HSV-2, like male circumcision, are warranted to be assessed, especially in MSM populations with low levels of circumcision and high incidence estimates of ulcerative STI.

HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men.

OBJECTIVES: Suppressive herpes simplex virus (HSV) therapy can decrease plasma, cervical, and rectal HIV-1 levels in HIV-1/HSV-2 co-infected persons. We evaluated the effect of HSV-2 suppression on seminal HIV-1 levels. DESIGN: Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2 men who have sex with men (MSM) in Lima, Peru, with CD4 >200 cells/microl randomly received valacyclovir 500 mg twice daily or placebo for 8 weeks, then the alternative regimen for 8 weeks after a 2-week washout. Peripheral blood and semen specimens were collected weekly. Anogenital swab specimens for HSV DNA were self-collected daily and during clinic visits. METHODS: HIV-1 RNA was quantified in seminal and blood plasma by TaqMan real-time polymerase chain reaction (RT-PCR) or Roche Amplicor Monitor assays. HSV and seminal cytomegalovirus (CMV) were quantified by RT-PCR. Linear mixed models examined differences within participants by treatment arm. RESULTS: Median CD4 cell count of participants was 424 cells/microl. HIV-1 was detected in 71% of 231 semen specimens. HSV was detected from 29 and 4.4% of swabs on placebo and valacyclovir, respectively (P < 0.001). Valacyclovir significantly reduced the proportion of days with detectable seminal HIV-1 (63% during valacyclovir vs. 78% during placebo; P = 0.04). Seminal HIV-1 quantity was 0.25 log10 copies/ml lower [95% confidence interval (CI) -0.40 to -0.10; P = 0.001] during the valacyclovir arm compared with placebo, a 44% reduction. CD4 cell count (P = 0.32) and seminal cellular CMV quantity (P = 0.68) did not predict seminal plasma HIV-1 level. CONCLUSIONS: Suppressive valacyclovir reduced seminal HIV-1 levels in HIV-1/HSV-2 co-infected MSM not receiving ART. The significance of this finding will be evaluated in a trial with HIV-1 transmission as the outcome.

Herpes simplex virus (HSV)-suppressive therapy decreases plasma and genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized, placebo-controlled, cross-over trial.

A randomized cross-over trial of herpes simplex virus type 2 (HSV-2)-suppressive therapy (valacyclovir, 500 mg twice daily, or placebo for 8 weeks, a 2-week washout period, then the alternative therapy for 8 weeks) was conducted among 20 Peruvian women coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) who were not on antiretroviral therapy. Plasma samples (obtained weekly) and endocervical swab specimens (obtained thrice weekly) were collected for HIV-1 RNA polymerase chain reaction. Plasma HIV-1 level was significantly lower during the valacyclovir arm, compared with the placebo arm (-0.26 log10 copies/mL, a 45% decrease [P < .001]), as was cervical HIV-1 level (-0.35 log10 copies/swab, a 55% decrease [P < .001]). Suppressive HSV-2 therapy has the potential to reduce HIV-1 infectiousness and slow HIV-1 disease progression.

Increased detection of HIV-specific T cell responses by combination of central sequences with comparable immunogenicity.

OBJECTIVE: To evaluate the recognition of computationally designed, centralized HIV-1 antigens derived from clade B, C and group M sequences by individuals infected with HIV-1-M clades B and C. METHODS: Three centralized sequences have been described - consensus, ancestor and center-of-tree - each of which attempts to minimize the genetic distance to circulating viruses. It is unclear whether any of these sequences affords an advantage for T cell recognition. The ability of centralized clade B and C and group M peptides to be targeted in ELISpot assays was assessed using samples from the United States, Peru, Barbados and South Africa. RESULTS: Each of the clade-specific centralized peptide sets was equally powerful in detecting cytotoxic T cell (CTL) responses. Importantly, combination of these sets detected significantly broader responses. Although broad responses were observed in populations from which few sequences informed the design of these centralized sequences, the genetic distance between local sequences and the respective test set was inversely associated with response rates. Furthermore, the CTL reactivity in clade C-infected subjects using clade B peptides was reduced relative to within-clade peptide responses, while responses to group M peptides were comparable to within-clade peptide responses in these individuals. CONCLUSIONS: All tested centralized antigens provided a similarly potent set of antigenic peptides. However, the significantly broader responses detected using the combination of sets highlight the importance of maximizing coverage of HIV-1 sequence diversity in vaccine preparations, as well as in the evaluation of CTL responses in HIV-1-infected individuals and those vaccinated.

Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection is common among human immunodeficiency virus (HIV)-infected persons, and HSV reactivation increases plasma and genital HIV-1 levels. We studied HIV-1 levels during HSV suppression in coinfected persons in a placebo-controlled crossover trial. METHODS: Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2-seropositive men who have sex with men in Lima, Peru, with CD4 cell counts >200 cells/ microL were randomized to receive either valacyclovir at 500 mg twice daily or placebo for 8 weeks, after which they underwent a 2-week washout period and then received the alternative regimen for 8 weeks. Specimens included daily anogenital swabs (for HSV DNA polymerase chain reaction [PCR]), thrice weekly rectal mucosal secretions (for HIV-1 RNA and HSV DNA PCR) obtained by anoscopy, and weekly plasma (for HIV-1 RNA PCR). Outcomes were rectal and plasma HIV-1 RNA levels by treatment arm. RESULTS: HIV-1 was detected in 73% of 844 rectal and 99% of 288 plasma specimens. HSV was detected in 29% and 4% of mucocutaneous specimens obtained during placebo and valacyclovir administration, respectively (P<.001). Valacyclovir resulted in a 0.16 (95% confidence interval [CI], 0.07-0.25; P=.0008; 33% decrease) log(10) copies/mL lower mean within-subject rectal HIV-1 level and a 0.33 (95% CI, 0.23-0.42; P<.0001; 53% decrease) log(10) copies/mL lower plasma HIV-1 level, compared with values for placebo. CONCLUSIONS: Valacyclovir significantly reduces rectal and plasma HIV-1 levels in HIV-1/HSV-2-coinfected men. HSV suppression may provide clinical benefits to persons not receiving highly active ART as well as public health benefits.

HIV-1, sexually transmitted infections, and sexual behavior trends among men who have sex with men in Lima, Peru.

OBJECTIVE: To assess and estimate trends in HIV, sexually transmitted infections (STIs), and sexual behavior among men who have sex with men (MSM) in Lima, Peru. DESIGN: Second-generation HIV sentinel surveillance surveys conducted in 1996, 1998, 2000, and 2002. METHODS: Adult men reporting sex with at least 1 man during the previous year were eligible to participate. Sexual behavior and serum HIV-1 and syphilis antibodies were assessed. HIV seroincidence was estimated by a sensitive/less-sensitive enzyme immunoassay strategy. Rectal and pharyngeal swabs for Neisseria gonorrhoeae culture and a first-void urine sample for urethral leukocytes for presumptive diagnosis of urethritis were obtained. Herpes simplex virus 2 (HSV-2) antibodies were measured in 2002. RESULTS: Although HIV prevalence increased from 18.5% to 22.3% from 1996 through 2002, bacterial prevalence declined significantly for syphilis (16.0% to 12.4%), early syphilis (8.6% to 3.4%), and rectal gonorrhea (5.1% to 0.2%). High HIV seroincidence was estimated, with the lowest (4.8%) incidence in 1998. In 2002, HSV-2 seroprevalence was 51.0%. After adjustment for age, education, and self-reported sexual identity, our data suggest that a yearly increase by 6% in the prevalence of HIV occurred among MSM in Lima, with a corresponding decline in syphilis (by 9%), early syphilis (by 18%), and rectal gonorrhea (by 64%). Condom use during last sexual intercourse increased by 26% each year with the most recent male steady partner and, among non-sex workers, by 11% with the most recent casual partner. CONCLUSIONS: HIV continued to spread among MSM in Lima even when a decline in bacterial STIs and increase in condom use were estimated to occur. Intensification of medical and behavior prevention interventions is warranted for MSM in Peru.

Association of herpes simplex virus type 2 infection and syphilis with human immunodeficiency virus infection among men who have sex with men in Peru.

BACKGROUND: We evaluated associations between human immunodeficiency virus (HIV) infection, herpes simplex virus type 2 (HSV-2) infection, and syphilis among men who have sex with men (MSM) in Peru. METHODS: A surveillance survey of 3280 MSM was conducted; sexual behavior was assessed with a structured computer-assisted self-interview, and serum antibody testing was performed for HIV, HSV-2, and Treponema pallidum. RESULTS: HIV, HSV-2, and syphilis seroprevalences of 13.9%, 46.3%, and 13.4% were detected, respectively. HSV-2 seroprevalence was twice as high in HIV-infected subjects (80.5%) than it was in HIV-uninfected subjects (40.8%) (P < .01), and HSV-2 seropositivity (adjusted odds ratio [AOR], 5.66) was found to be strongly associated with HIV infection. In addition, homosexual self-definition (AOR, 3.12), exchange of sex for money (AOR, 1.61), unprotected sex (no condom) (AOR, 2.81), history of sex work (AOR, 1.89), oral receptive sex (AOR, 1.43), and cocaine use before/during sex (AOR, 2.53) within the preceding 6 months, as well as such sexually transmitted infections (STIs) and STI syndromes as proctitis (AOR, 2.80), genital ulcer disease (GUD) (AOR, 2.06), prior syphilis (AOR, 2.64), genital warts (AOR, 1.70), and self-reported STIs within the preceding 6 months (AOR, 1.61), were also found to be significant predictors of HIV infection. CONCLUSIONS: We found a strong association between HSV-2 seropositivity and HIV infection. Intervention measures against GUD due to HSV-2 infection and syphilis, such as routine testing, early detection, HSV-2 suppressive treatment, and condom distribution, need to be enhanced as part of STI prevention strategies at a national level to effectively reduce HIV infection among MSM in Peru.

Relative dominance of Gag p24-specific cytotoxic T lymphocytes is associated with human immunodeficiency virus control.

Conflicting data on the role of total virus- and protein-specific cytotoxic-T-lymphocyte (CTL) responses in the control of human immunodeficiency virus (HIV) disease progression exist. We present data generated from a Peruvian cohort of untreated, clade B-infected subjects, demonstrating that the proportion of Gag-specific, and in particular p24-reactive, CTL responses among the total virus-specific CTL activity is associated with individuals' CD4 counts and viral loads. Analyses in a second cohort in the United States confirm these findings and point towards a dominant role of Gag-specific immunity in effective control of HIV infection, providing important guidance for HIV vaccine development.

Higher concentration of HIV RNA in rectal mucosa secretions than in blood and seminal plasma, among men who have sex with men, independent of antiretroviral therapy.

High levels of human immunodeficiency virus (HIV) in rectal secretions and semen likely increase the risk of HIV transmission. HIV-infected men who have sex with men made 2-3 study visits, over 4 weeks, to assess rectal, seminal, and plasma levels of HIV RNA. Mixed-effects models estimated the effect of factors on HIV shedding. Twenty-seven (42%) of 64 men were receiving antiretroviral therapy (ART); regardless of ART use, median HIV RNA levels were higher in rectal secretions (4.96 log(10) copies/mL) than in blood plasma (4.24 log(10) copies/mL) or seminal plasma (3.55 log(10) copies/mL; P<.05, each comparison). ART was associated with a 1.3-log(10) reduction in rectal HIV RNA in a model without plasma HIV RNA; with and without plasma RNA in models, ART accounted for a >1-log(10) decrease in seminal HIV RNA levels. Thus, controlling for plasma HIV RNA, ART had an independent effect on seminal, but not rectal, HIV levels.

Factors associated with oropharyngeal human immunodeficiency virus shedding.

Orogenital transmission of human immunodeficiency virus (HIV) is considered to be inefficient, and infectious HIV is rarely detected in saliva. To evaluate the posterior oropharynx as a source of HIV shedding, we studied 64 HIV-infected men who have sex with men in Seattle, Washington, and Lima, Peru. In multivariate analysis, receipt of antiretroviral therapy, higher CD4 cell count, and history of tonsillectomy were predictors of lower pharyngeal HIV RNA levels.

Pilot study of COBAS PCR and ligase chain reaction for detection of rectal infections due to Chlamydia trachomatis.

We tested rectal specimens from men who have sex with men for Chlamydia trachomatis by using COBAS PCR (Roche Diagnostics) and ligase chain reaction LCR (Abbott laboratories) and compared three PCR specimen-processing procedures. Chlamydiae were detected by one or more procedures in 22 of 186 specimens. All three PCR tests were positive for 17 specimens, all of which also tested positive by LCR.