Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. METHODS: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. RESULTS: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). CONCLUSIONS: Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

HIV-I reverse transcriptase variation in plasma and genital secretion of antiretroviral-naive females.

The reverse transcriptase (RT) enzyme of HIV type 1 (HIV-1) is largely targeted by the host immune selection pressure and would differ in the anatomical compartments, thereby having a drastic impact on viral quasi-species evolution. The HIV-1 RT region sequenced from plasma and genital secretions of 8 antiretroviral treatment (ART)-naive females was analyzed for the pattern of amino acid mutations and the ratio of synonymous and nonsynonymous substitutions to determine whether it is under different selection pressure in both the compartments. Phylogenetic and mutational analysis of the HIV-1 RT in plasma and genital secretions of HIV-1-infected ART-naive females showed limited variation likely reflecting the absence of differential selection pressure and therefore genetic variation in these compartments.

Oral candidal carriage, salivary lysozyme levels, and their relationship with CD4 count in HIV-infected patients.

AIM: The aim of the present study was to compare the lysozyme concentration and candidal count in saliva between HIV-seropositive and HIV-negative individuals, and to correlate the relationship between lysozyme concentrations, candidal count, and CD4 count in HIV patients. METHODS: A study was conducted in 90 HIV-seropositive patients (subgroups: 1 [CD4 ≥ 500 cells/µL], 2 [CD4 200-499 cells/µL], and 3 [CD4 ≤ 200 cells/µL] and 30 HIV-negative individuals. A total of 6 mL unstimulated saliva was collected and stored at -80°C. Samples were centrifuged and divided into two portions of 600 µL each. One portion was used for the candidal assay and the other for the lysozyme assay using ready-made kits. Student's independent t-test and Karl Pearson correlation coefficient were used for the statistical analysis. RESULTS: There was a significant increase (P < 0.001) in lysozyme levels and the candidal count in the saliva of HIV-positive individuals compared with the HIV-negative individuals. A significant increase (P < 0.004) in the salivary candidal count was observed in the HIV subgroups 1-3. There was a significant negative correlation (P < 0.01) between the CD4 and candidal counts in subgroup 1 (P < 0.02) and between the lysozyme concentration and CD4 count in subgroup 3. There was no correlation between the lysozyme concentration and oral candidal carriage. CONCLUSIONS: An association exists between the lysozyme concentration and specific immunity. Yeast colonization serves as a marker of immunodeficiency in HIV disease progression.

Short communication: Nucleotide variation and positively selected sites in HIV type 1 reverse transcriptase among heterosexual transmission pairs.

Mutations in the env gene of HIV-1 have been the primary focus in most epidemiologically related cohort studies of virus evolution and very limited studies have focused on the reverse transcriptase (RT) region, the primary target of antiretroviral therapy (ART). Hence, we measured the selection pressure and searched for the positively selected sites in the RT sequences amplified from HIV-1-infected heterosexual transmission pairs. Married couples (n = 10) who were ART naive were included in this study. Phylogenetic analysis, the measurement of synonymous and nonsynonymous ratio (dN/dS) and the interpatient nucleotide variation, was done. Phylogenetic analysis demonstrated distinct subclusters of the RT sequences from heterosexual transmission pairs and the median (IQR) nucleotide variation between the epidemiologically related transmission pairs was significantly (p < 0.001) lower [0.01% (0.01-0.02%)] compared to the epidemiologically unrelated transmission pairs [0.04% (0.03-0.04%)]. The ratio of dN/dS was <1 and codons 135, 162, 166, 207, and 211 were positively selected in >50% of the donor and recipient RT sequences. Purifying selection pressure and low nucleotide variation in the RT sequences between epidemiologically related transmission pairs highlight its essential role in HIV-1 replication. The effect of the RT positively selected mutations that persist over time following transmission between individuals needs to be studied to determine the fitness cost of the mutations in vivo, which may possibly represent good targets for inclusion in HIV-1 vaccines.

Analysis of selection pressure and mutational pattern of HIV type 1 reverse transcriptase region among treated and nontreated patients.

Variation of the HIV-1 subtype C reverse transcriptase region (RT) resulting in response to the selective pressures of drug therapy remains poorly characterized. Here, we compared the genetic variation resulting in the presence and absence of antiretroviral drug selective pressures on HIV-1 subtype C RT among nontreated and treated patients. The nucleotide variability, nonsynonymous and synonymous ratio, and the positively selected mutations were determined by comparing the RT sequences isolated at two time points among nontreated (baseline and follow-up) and treated patients (baseline and treatment failure). Compared to the nontreated patients, the intrapatient nucleotide variability, the number of nonsynonymous and synonymous substitutions was significantly higher among the treated patients. Among the mutations positively selected, the frequency of D121Y, I135R, and Q207E increased and the frequency of mutation S48T decreased significantly during treatment failure. Further studies are essential to discover the role of these mutations during treatment in HIV-1 subtype C.

Atypically distributed cutaneous lesions of Norwegian scabies in an HIV-positive man in South India: a case report.

INTRODUCTION: Immune-compromised subjects, especially those with underlying HIV disease, are prone to be infected with Norwegian scabies, where the cutaneous lesions are classically distributed over the extremities. CASE PRESENTATION: We report the case of an HIV-positive 16-year-old man with severe crusted Norwegian scabies initially misdiagnosed as a dermal fungal infection. The patient had extensive, generalized, thick, hyperkeratotic, crusting, yellowish papule lesions distributed on the entire body from his scalp to his toes.The patient was started with Ivermectin and topical Permethrin, which eventually resulted in complete resolution. Interestingly, despite quarantining efforts, one of the patient's acquaintances and a healthcare worker acquired the symptoms of itching. CONCLUSION: This atypical presentation of Norwegian scabies emphasizes the need to include scabies in the differential diagnosis when HIV-infected patients present with crusted, generalized cutaneous lesions.