Serial Viral Load Measurements Research Articles

Serial type-specific human papillomavirus (HPV) load measurement allows differentiation between regressing cervical lesions and serial virion productive transient infections.

Persistent high-risk human papillomavirus (HPV) infection is strongly associated with the development of high-grade cervical intraepithelial neoplasia (CIN) or cancer. Not all persistent infections lead to cancer. Viral load measured at a single time-point is a poor predictor of the natural history of HPV infections. However the profile of viral load evolution over time could distinguish nonprogressive from progressive (carcinogenic) infections. A retrospective natural history study was set up using a Belgian laboratory database including more than 800,000 liquid cytology specimens. All samples were submitted to qPCR identifying E6/E7 genes of 18 HPV types. Viral load changes over time were assessed by the linear regression slope. Database search identified 261 untreated women with persistent type-specific HPV DNA detected (270 infections) in at least three of the last smears for a average period of 3.2 years. Using the coefficient of determination (R²) infections could be subdivided in a latency group (n = 143; R² < 0.85) and a regressing group (n = 127; R² ≥ 0.85). In (≥3) serial viral load measurements, serial transient infections with latency is characterized by a nonlinear limited difference in decrease or increase of type-specific viral load (R² < 0.85 and slopes between 2 measurements 0.0010 and −0.0010 HPV copies/cell per day) over a longer period of time (1553 days), whereas regression of a clonal cell population is characterized by a linear (R² ≥ 0.85) decrease (−0.0033 HPV copies/cell per day) over a shorter period of time (708 days; P < 0.001). Using serial HPV type-specific viral load measurements we could for the first time identify regressing CIN2 and CIN3 lesions. Evolution of the viral load is an objective measurable indicator of the natural history of HPV infections and could be used for future triage in HPV-based cervical screening programs.

Virologic Response Using Directly Observed Therapy in Adolescents With HIV: An Adherence Tool

Virologic response to highly active antiretroviral therapy (HAART) treatment of HIV infection depends on viral sensitivity to antiretrovirals and excellent medication adherence. Adolescents with vertically acquired HIV may require complicated regimens because of significant treatment experience and often have poor medication adherence. A retrospective chart review identified five adolescents with vertically acquired HIV and plasma HIV viral load rebound or nonresponse on a stable HAART regimen followed by a period of directly observed therapy (DOT) in a clinic or hospital setting with serial viral load measurements. Four subjects had a virologic response (mean decline, 1.15 log10) after DOT. A response to HAART can be seen despite antiretrovirals resistance using DOT and treatment-experienced patients seemingly unresponsive to HAART may be nonadherent even with reassuring adherence measures. A period of clinic-monitored DOT may allow diagnosis of nonadherence, discussion of medication barriers, and avoidance of unnecessary medication changes.

ADVANCES IN HIV TREATMENT AND TREATMENT TOXICITIES

Among the different classes and complexities of antiretroviral regimens, maximal viral suppression, sustained durability, increased CD4 count, decreased evolving resistance, and fewer side effects combined with increased compliance resulting in decreased morbidity and mortality remain the goals of therapy. Serial viral load measurements help best guide the direction of therapy. According to the CDC 20% fewer people died of HIV in 1998 compared to 1997 in the United States. HAART, although expensive (sometimes exceeding $20,000 per year), is not readily available to 95% of the estimated 36 million HIV-infected people in the world. HAART therapy commonly consists of two NRTIs and a protease inhibitor, but other combination regimens exist. The disadvantage of HAART therapy is that antiretroviral agents are not virucidal, thus eradication with these drug cocktails cannot be achieved. When HAART therapy is stopped, viral loads return to pre-treatment levels. New drug classes under investigation may completely prevent fusion between the HIV virus and healthy cells. For now, the epidemic can only be controlled with good public awareness, such as education, condom use, or abstinence. Because a cure does not seem immediately foreseeable, an effective prophylactic vaccine may afford protection. Defined treatment regimens exist for occupational postexposure prophylaxis. Ultimately, an expert in the field should be involved in manipulating drug regimens; however, dermatologists remain an integral part of the health care team because most HIV patients experience cutaneous manifestations related either to their HIV or to their drug therapy.