Herpes simplex virus type 2 and HIV disease progression: a systematic review of observational studies.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is a common co-infection among HIV-infected adults that is hypothesized to accelerate HIV disease progression. METHODS: We searched Medline, EMBASE, relevant conference proceedings (2006-12) and bibliographies of identified studies without language restriction for cohort studies examining the impact of HSV-2 on highly active antiretroviral therapy-untreated HIV disease in adults. The exposure of interest was HSV-2 seropositivity or clinical/laboratory markers of HSV-2 activity. The primary outcome was HIV disease progression, defined as antiretroviral initiation, development of AIDS/opportunistic infection, or progression to CD4 count thresholds (≤ 200 or ≤ 350 cells/mm(3)). Secondary outcomes included HIV plasma viral load and CD4 count. RESULTS: Seven studies were included. No definitive relationship was observed between HSV-2 seropositivity and time to antiretroviral initiation (n=2 studies), CD4 ≤ 350 (n=1), CD4 ≤ 200 (n=1), death (n=1), viral load (n=6) or CD4 count (n=3). Although two studies each observed trends towards accelerated progression to clinical AIDS/opportunistic infection in HSV-2 seropositives, with pooled unadjusted hazard ratio=1.85 (95% CI=1.12,3.06; I2=2%), most OIs observed in the study for which data were available can occur at high CD4 counts and may not represent HIV progression. In contrast, a single study HSV-2 disease activity found that the presence of genital HSV-2 DNA was associated with a 0.4 log copies/mL increase in HIV viral load. CONCLUSIONS: Despite an observation that HSV-2 activity is associated with increased HIV viral load, definitive evidence linking HSV-2 seropositivity to accelerated HIV disease progression is lacking. The attenuating effects of acyclovir on HIV disease progression observed in recent trials may result both from direct anti-HIV activity as well as from indirect benefits of HSV-2 suppression.

Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study.

BACKGROUND: Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) C(min) and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations. METHODS: HIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for C(min) and Cmax were drawn weekly for 3 weeks. The ratio of each individual's median C(min) and Cmax to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed C(min) and Cmax ratios. RESULTS: Data from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral C(min) and Cmax ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher C(min). No significant correlates for Cmax were found. CONCLUSIONS: Compared to historical control data, C(min) in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral C(min) ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations. TRIAL REGISTRATION: NCT00433979.

Otosyphilis in HIV-coinfected individuals: a case series from Toronto, Canada.

We sought to identify and review the clinical features and treatment outcomes of eight recent cases of otosyphilis in HIV-positive patients seen in Toronto. All patients reported tinnitus, and seven (87.5%) reported subjective hearing loss. Not taking auditory findings into consideration, four patients would be classified as having secondary syphilis, three patients as having early latent syphilis, and one patient as having latent syphilis of unknown duration. The median CD4 cell count was 370 x 10(6)/L. All patients were treated with intravenous aqueous penicillin G with regimens recommended for the treatment of neurosyphilis; four patients received adjunctive steroids. All eight patients experienced improvement in tinnitus and four of the seven (57.1%) patients with symptomatic hearing loss also experienced improvement. Otosyphilis can occur in HIV-positive individuals despite high CD4 cell counts, and is potentially reversible. Increased awareness of uncommon manifestations of syphilis in high-risk individuals is warranted to prompt appropriate investigation and treatment.