Self-reported sexual dysfunction is frequent among HIV-infected persons and is associated with suboptimal adherence to antiretrovirals.

Increased occurrence of sexual dysfunction (SD) among patients treated with highly active antiretroviral therapy (HAART) has been reported. To assess prevalence of self-reported SD and to identify factors related to this alteration with special focus to its relationship with adherence behavior, we conducted an intercohort analysis among HIV-infected persons treated with HAART. In an anonymous questionnaire investigating HAART nonadherence, patients were asked to report the occurrence of dysfunction in sexual activity over the previous 4 weeks. Among 612 participants, 125 (21%) reported some degree of SD. "Moderate"/"severe" alterations were reported in 6% and were independently associated with self-reported worsening of viro-immunological parameters (OR 3.90; 95% CI 1.08-14.18), higher symptom score (OR 1.13; 95% CI 1.05-1.22), and reporting abnormal fat accumulation (OR 4.33; 95% CI 1.55-12.11). Furthermore, nonadherent persons had an increased risk of SD (OR 3.44; 95% CI 1.30-9.08). In conclusion, patients' perceived SD represents a relevant problem for HIV-infected persons treated with antiretrovirals and is strongly associated with suboptimal HAART adherence.

Mutations in HIV-1 reverse transcriptase potentially associated with hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors: effect on response to efavirenz-based therapy in an urban observational cohort.

BACKGROUND: Hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was described in association with reverse-transcriptase (RT) mutations conferring resistance to nucleoside reverse-transcriptase inhibitors (NRTIs). We evaluated the effect of RT mutations associated with hypersusceptibility to NNRTIs on the response to efavirenz-based therapy. METHODS: We analyzed an observational database of patients for whom highly active antiretroviral therapy failed and who received genotypic resistance testing-guided therapy, either efavirenz or protease inhibitor (PI) based. Study end points were achievement of virus load <80 copies/mL, achievement of virus load <80 copies/mL without rebound to >500 copies/mL, and changes in CD4 cell counts. RESULTS: The baseline RT mutations M41L, M184V, L210W, and T215Y and the M41L/T215Y and M41L/T215Y/M184V combinations were associated with virological suppression for efavirenz-treated patients, whereas, for PI-treated patients, only the M184V mutation was associated with virological suppression, and the L210W mutation showed a negative correlation; no correlation was found between any mutation and virological response without rebound. CONCLUSIONS: The M41L, M184V, L210W, and T215Y mutations were associated with a better, although transient, virological outcome in patients treated with efavirenz-based regimens.

Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy.

Among 470 patients with acquired immune deficiency syndrome and/or human immunodeficiency virus infection (HIV/AIDS) who underwent genotype resistance testing (GRT) after the failure of therapy, 17 (3.6%) harbored the Q151M mutation. The Q151M mutation was associated with younger age, lower CD4(+) lymphocyte count, higher HIV RNA level, and treatment with >2 pre-GRT regimens. By contrast, the Q151M mutation was inversely associated with lamivudine administration. A full reversion of the Q151M mutation was observed in 5 of 5 patients who underwent treatment interruption after GRT. The reversion was followed by a response to salvage therapy in 4 (80%) of 5 patients.

Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation.

OBJECTIVE: M184V/I mutation is associated with high-level phenotypic resistance to lamivudine (3TC). The aim of the present analysis was to correlate the time of appearance/disappearance of M184V/I with duration of 3TC treatment. METHODS: Overall, 211 patients were selected from a database of HIV patients undergoing genotypic resistance test after virological failure of HAART regimens in two major reference centres in Rome between 1999 and 2001. At the time of genotyping, 120 of them (56.9%) were failing a 3TC-including HAART, while 91 (43.1%) received 3TC only in previous HAART. Duration of the current 3TC-containing regimen and the time from the end of last 3TC treatment to genotypic resistance test (GRT) were analysed. RESULTS: Among patients currently undergoing 3TC-containing HAART, the prevalence of M184V/I was 82.5% (78.3/4.2%, respectively) and significantly associated to current 3TC use at GRT. Prevalence of M184V/I was associated to longer history of 3TC (from 47.1% in patients treated with 3TC for <6 months, to 84.0% among those treated for 7-12 months; 100.0% of patients with >42 months of current 3TC carried M184V. At logistic regression analysis, the rate of increase of M184V/I in 3TC-failing patients was statistically significant (OR: 1.066 per month of current 3TC therapy, 95% CI: 1.020-1.114, P<0.01), suggesting a 6.6% monthly increase of probability of M184V/I. Among patients who interrupted 3TC, overall prevalence of M184V/I was 23.1%: proportion of patients carrying the M184V/I dropped from 83.3% among those who interrupted 3TC from < or = 3 months, to 56.3, 20, 10.5 and 0% for those interrupting 3TC from 6, 12, 24 and > or = 24 months, respectively. At logistic regression, the rate of disappearance of M184V/I was also statistically significant (OR: 0.883 per month, 95% CI: 0.804-0.970, P=0.01), indicating a 11.7% monthly decrease of probability of M184V/I after 3TC interruption. CONCLUSIONS: Dynamics of appearance/disappearance of M184V/I mutation is rapid after 3TC failure/interruption, suggesting ease of development of such a mutation, but also suggesting a remarkable growth disadvantage for HIV. From the clinical perspective, recycling of drugs whose antiviral activity is affected by M184V mutation can be successful after appropriate drug wash-out, also in heavily pretreated patients.

Depression is a risk factor for suboptimal adherence to highly active antiretroviral therapy.

Affective disorders have been reported as the most common mental health problem in persons with HIV infection. Depression has a significant impact on the quality of life of persons living with HIV and AIDS and is associated with HIV disease progression and mortality, even after controlling for sociodemographic and clinical characteristics and substance abuse. Depression has been also reported as one of the main causes of poor adherence with antiretroviral regimens. However, no published investigation has specifically focused on the relationship between depression and adherence to antiretroviral therapy. Nonetheless, information on the association between depressive symptoms and adherence may be gathered from investigations carried out to explore determinants of adherence with antiretroviral therapy. Findings from available studies show a substantial and consistent relationship between adherence to antiretroviral regimens and depression. Early recognition and proper management of depressive comorbidity could be an effective intervention strategy to improve adherence and may make a difference in the quality of life, social functioning, and disease course of people with HIV.