Unresolved issues in the management of human papillomavirus-associated mucosal high-grade pre-cancers.

This article reviews human papillomavirus-associated mucosal high-grade pre-cancers and their management. It examines pre-cancer classification systems, the natural history of HPV-associated pre-cancers, the various types of management and treatment for HPV pre-cancers, the various mucosal site-specific considerations, and then some of the unresolved issues. Different conclusions are reached for each of the relevant mucosal sites, which are cervix, vagina, vulva, anus, penis and oro-pharynx, and indeed there are differing volumes of evidence relating to each of these sites, and thus differing degrees of certainty/uncertainty in the recommendations.

HPV vaccination in HIV infection.

Persons with HIV are at increased risk of HPV infection, HPV disease, and HPV-related cancers compared to HIV negative persons. In persons with HIV, immune responses to vaccination are often sub-optimal, and while these improve with ART, they often remain lower and decline more rapidly than in HIV-negative individuals. Although the evidence base to support the immunogenicity of HPV vaccines in HIV + ve persons is reasonable, the evidence base to support the efficacy of HPV vaccines in HIV + ve individuals is inconsistent. There is one study in HIV + ve men who have sex with men (MSM) which showed no effect, and two other studies, one in HIV + ve women and one in HIV + ve adolescents that showed reduced effectiveness. All these effectiveness studies used Gardasil 4 (G4). Two studies in HIV + ve persons have shown superior immunogenicity of Cervarix (which uses a TLR4 agonist adjuvant) compared to G4. Studies of Hepatitis B vaccines in HIV + ve persons have shown that either (i) increased number of doses (ii) increased vaccine dose, or (iii) TLR agonist adjuvanted vaccines, all produce increased immunogenicity compared to standard vaccine regimes. Therefore, questions remain as to optimal HPV vaccine regimes in HIV and further clinical trials with different HPV vaccine regimes are needed.

Neurocognitive function in HIV infected patients on antiretroviral therapy.

OBJECTIVE: To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN: We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE: NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS: Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS: In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY: ClinicalTrials.gov, NCT01230580.