Journal of AIDS & Clinical Research

Background: Emergence of HIV-1 drug resistance is at times an inevitable and anticipated consequence of antiretroviral therapy (ART) failure. We examined drug resistance patterns and virus re-suppression among subtype C-infected South African patients receiving first-line ART. Methods: Treatment records of 431 patients on NNRTI-containing regimens for a median of 45 months were analyzed. Patients with viral load (VL) >400 copies/mL were followed and drug resistance mutations (DRM) were re-assessed. Associations between clinical/demographic measures and drug resistance/virologic outcomes were examined using Fisher exact and ordinal and logistic regression. Results: Ten percent of patients (43/431) were viremic at enrollment (98%) sequences were obtained from 38/43. Of those, 82% had 1-7 DRM. In bivariate analysis remote exposure to single-dose nevirapine or prior ART; higher CD4 counts; lower VL; and >6 months of virologic failure were significantly associated with number of DRM. Of 25 viremic patients followed for a median of 8 months on a continued first-line regimen, 12 (48%) re-suppressed, six with K103N and three with M184V. Thirteen (52%) had continued virologic failure which was significantly associated with detectable VL >6 months prior to enrollment and number of DRM. Conclusion: Among these HIV-1 subtype C-infected patients, DRM numbers and patterns were associated with prior exposure to sub-optimal ART, adherence and duration of virologic failure. Viral re-suppression in the presence of K103N and M184V challenges assumptions about drug resistance. In resource-limited settings, where genotyping and alternative drug options are unavailable, continuing first-line treatment, reinforcing adherence and regular virologic monitoring may be effective even after virologic failure.

Incomplete immune reconstitution and persistent immune system hyperactivation in spite of highly active antiretroviral therapy continue to be a challenge. Both facts may lead to an increased risk for AIDS-defining and non AIDS-defining clinical conditions and may also promote atherogenesis and liver fibrogenesis in HIV and hepatitis C virus-coinfected patients. In this article, the use of new markers to assess immune reconstitution and immune activation and the incidence and clinical consequences of immunediscordant response to antiretroviral therapy are addressed. Likewise, the impact of immune dysfunction on atherogenesis and liver fibrogenesis are reviewed. Finally, it is discussed whether therapy with drugs belonging to the family of CCR5 inhibitors may provide additional immunological benefit in HIV-infected patients.