July 2004

Mutations in HIV-1 Reverse Transcriptase Potentially Associated With Hyper-Susceptibility to Nonnucleoside Reverse Transcriptase Inhibitors: Effect on Response to Efavirenz-Based Therapy in an Urban Observational Cohort

Tozzi V, Zaccarelli M, Narciso P, et al.

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 endpoints 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. [J Infect Dis 2004;189(9):1688-95.]

Changes in Total Lymphocyte Count as a Surrogate for Changes in CD4 Count Following Initiation of HAART: Implications for Monitoring in Resource-Limited Settings

Mahajan AP, Hogan JW, Snyder B, et al.

Background: A major obstacle to the administration of highly active antiretroviral therapy (HAART) in resource-limited settings is the high cost of CD4 count testing. The total lymphocyte count (TLC) has been proposed as a surrogate marker to monitor immune response to therapy.

Objective: To assess, in a developed country setting, the capability and clinical utility of TLC change as a surrogate marker for CD4 count change in monitoring patients on HAART.

Methods: Longitudinal co-variation between changes in TLC and concomitant changes in CD4 count following the initiation of HAART was examined using a retrospective cohort study of 126 HIV-positive patients attending The Miriam Hospital at Brown University in Providence, Rhode Island. Analyses included evaluation of the direction of TLC change as a marker for direction of CD4 change, using sensitivity and specificity; evaluation of absolute change in TLC as a marker for benchmark changes in CD4 (>50 over six months, >100 over 12 months), using receiver-operator characteristic (ROC) curves; and a regression model of change in TLC as a function of change in CD4, to understand within-individual variation of longitudinal TLC measures.

Results: In the first 24 months of HAART, the sensitivity of a TLC increase as a marker for CD4 count increase over the same time period ranged from 86-94 percent, and the specificity ranged from 80-85 percent. The median change in TLC among patients with a CD4 count rise of >100 cells/mm3 at one year of HAART was +766 cells/mm3 while that of patients with a CD4 count rise of 3 was +100 cells/mm3. The area under the corresponding ROC curve was 0.89, suggesting that change in TLC discriminates well between those with one-year CD4 change of >+100 versus those with change 3 change in CD4 count was 7.3 (SE 1.2, P<0.001). The degree of this association varied from individual to individual but was positive for all individuals.

Conclusions: Within the first two years of HAART, the direction of change in TLC appears to be a strong marker for direction of concomitant change in CD4 count (sensitivity 86-94 percent and specificity 80-85 percent, depending on length of interval). Positive and negative predictive values depend on the proportion of CD4 changes that are positive. In this cohort, that proportion is 87.9 percent, which yields high positive predictive value (96-98 percent) but lower negative predictive value (43-63 percent). Findings from the regression model suggest that taking multiple measurements of TLC at more frequent intervals may reduce variability and potentially improve predictive accuracy. [J Acquir Immune Defic Syndr 2004;36(1):567-575.]

Oral Manifestations of HIV Infection in Relation to Clinical and CD4 Immunological Status in Northern and Southern Thai Patients

Kerdpon D, Pongsiriwet S, Pangsomboon K, et al.

Objectives: To assess prevalence and variations in the oral manifestations of HIV in HIV-infected subjects in southern Thailand (a new HIV epidemic) and northern Thailand (a mature epidemic), and the association with age, sex, risk behaviors, CD4 count, and medication used.

Subjects and Methods: A total of 102 and 135 HIV-infected individuals were enrolled in northern and southern hospitals, respectively. Oral and hematological examination was performed after sociodemographic interview of the patients. Clinical history was retrieved from patients' medical records.

Results: Oral candidiasis (OC, 55 percent), oral hairy leukoplakia (OHL, 21 percent), and HIV-associated periodontal disease (14 percent) were among the most common oral lesions in southern Thailand. OHL (38 percent), OC (25 percent), and HIV-associated periodontal disease (15 percent) were the three most common lesions in the north. A significant association was found between any oral lesion, OC, particularly the pseudomembranous type (PC), and CD4 <200 cells/mm3 at both sites. A negative relationship was found between systemic antifungal treatment and OC including PC and erythematous candidiasis (EC) in the southern data. OHL showed a positive relationship with male sex and a negative relationship with antiretroviral treatment in the northern site. Younger age and being a current smoker were positively associated with oral lesions in the southern group.

Conclusion: OC, particularly PC, could be useful as a marker for immunosuppression, particularly where CD4 count cannot be determined routinely. Antifungal treatment is of benefit in the subjects who cannot afford highly active antiretroviral therapy (HAART). [Oral Dis 2004;10(3):138-44.]

Gender-Based Violence, Relationship Power, and Risk of HIV Infection in Women Attending Antenatal Clinics in South Africa

Dunkle KL, Jewkes RK, Brown HC, et al.

Background: Gender-based violence and gender inequality are increasingly cited as important determinants of women's HIV risk; yet empirical research on possible connections remains limited. No study on women has yet assessed gender-based violence as a risk factor for HIV after adjustment for women's own high-risk behaviors, although these are known to be associated with experience of violence.

Methods: We did a cross-sectional study of 1,366 women presenting for antenatal care at four health centers in Soweto, South Africa, who accepted routine antenatal HIV testing. Private face-to-face interviews were done in local languages and included assessment of sociodemographic characteristics, experience of gender-based violence, the South African adaptation of the Sexual Relationship Power Scale (SRPS), and risk behaviors including multiple, concurrent, and casual male partners, and transactional sex.

Findings: After adjustment for age and current relationship status and women's risk behavior, intimate partner violence (odds ratio 1.48, 95 percent CI 1.15-1.89) and high levels of male control in a woman's current relationship as measured by the SRPS (1.52, 1.13-2.04) were associated with HIV seropositivity. Child sexual assault, forced first intercourse, and adult sexual assault by non-partners were not associated with HIV serostatus.

Interpretation: Women with violent or controlling male partners are at increased risk of HIV infection. We postulate that abusive men are more likely to have HIV and impose risky sexual practices on partners. Research on connections between social constructions of masculinity, intimate partner violence, male dominance in relationships, and HIV risk behaviors in men, as well as effective interventions, are urgently needed. [Lancet 2004;363(9419):1415-1421.]

Back to the July 2004 issue of IAPAC Monthly.

This article was provided by International Association of Physicians in AIDS Care. It is a part of the publication IAPAC Monthly.