Switch from tenofovir to raltegravir increases low bone mineral density and decreases markers of bone turnover over 48 weeks.

BACKGROUND: Tenofovir, particularly when given with a ritonavir-boosted protease inhibitor (rPI), reduces bone mineral density (BMD) and increases bone turnover markers (BTMs), both of which are associated with increased fracture risk. Raltegravir has not been associated with bone loss. METHODS: In an open-label, nonrandomized, pilot study, tenofovir was switched to raltegravir in adults also receiving a rPI for at least 6 months with a spine or hip T-score ≤ -1.0 and plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 3 months. The primary endpoint was BMD change by dual-energy X-ray absorptiometry. Student's paired t-test was used to compare continuous variables. Factors associated with BMD increase were assessed using linear regression. RESULTS: Thirty-seven patients were enrolled in the study: 97% were male, the mean age was 49 years, the mean T-scores were -1.4 (spine) and -1.3 (total left hip), and the mean tenofovir treatment duration was 3.1 years. BMD increases were significant at weeks 24 and 48. At week 48, spine BMD increased by 3.0% [95% confidence interval (CI) 1.9, 4.0%; P < 0.0001] and left total hip BMD increased by 2.5% (95% CI 1.6, 3.3%; P < 0.0001). BTMs (N-telopeptide, osteocalcin and bone alkaline phosphatase) all decreased significantly at week 24 (P ≤ 0.0017). There were no raltegravir-related serious or grade 3-4 adverse events. HIV viral load remained <50 copies/mL plasma on raltegravir/rPI therapy. CONCLUSIONS: Switching virologically suppressed HIV-infected adults with low BMD taking an rPI from tenofovir to raltegravir was safe and significantly improved hip and spine BMD and reduced markers of bone turnover over 48 weeks.

Raltegravir-emtricitabine-tenofovir as HIV nonoccupational post-exposure prophylaxis in men who have sex with men: safety, tolerability and adherence.

OBJECTIVES: Three-drug nonoccupational post-exposure prophylaxis (NPEP) typically includes co-formulated emtricitabine-tenofovir (FTC-TDF) and a protease inhibitor. However, protease inhibitors can cause significant toxicities, can interact with prescribed and illicit drugs, and work late in the viral cycle. Agents that act before viral integration into host DNA may have efficacy advantages. Raltegravir (RAL) is a good candidate for NPEP as it has few side effects or drug interactions and acts prior to HIV integration. The objective of this study was to investigate the use of RAL in 3-drug NPEP in terms of safety, adherence and tolerability. METHODS: We evaluated 28 days of RAL-FTC-TDF treatment in 86 men and FTC-TDF treatment in 34 men eligible for three- and two-drug NPEP, respectively. We assessed adherence (compared between groups and with nonstudy controls) and clinical and adverse events at weeks 1, 2 and 4, and efficacy at week 12. Analyses were by intention to treat, excluding from the adherence analysis subjects who ceased NPEP because their source was HIV-uninfected. RESULTS: No participant became infected with HIV. For RAL-FTC-TDF and FTC-TDF, regimen completion rates were 92% and 91% and medication adherence rates were 89% and 90%, respectively. Eight (9%) RAL recipients developed mild myalgias, with four developing transient grade 4 elevations in creatine kinase (two developed both), all of which improved to grade 2 or less by week 4 without RAL discontinuation. Eight prescribed and 37 potential illicit drug interactions with a protease inhibitor were avoided by use of RAL. CONCLUSIONS: RAL-FTC-TDF is well tolerated as NPEP, results in high levels of adherence and avoids potential drug-drug interactions. Patients and clinicians should be aware of the potential for acute muscle toxicity when RAL is used as NPEP.

Anal intraepithelial neoplasia and squamous cell carcinoma in HIV-infected adults.

Anal cancer is one of the most common non-AIDS-defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV-infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV-related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV-infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV-infected adults.

Transmission of triple-class, drug-resistant HIV-1 in Australia.

We report the first two cases of transmitted triple-class, drug-resistant HIV-1 in Australia. Baseline testing of a newly diagnosed man showed four reverse transcriptase resistance mutations (affecting two drug classes) and six protease resistance mutations. A source patient was identified, and a likely second case newly infected 1 year later, suggesting sequential transmission. This raises therapeutic implications for the individual patients, as well as public health concerns.