To assess associations between the timing of hepatitis B virus (HBV) immunization relative to human immunodeficiency virus (HIV) diagnosis and vaccine effectiveness, US Military HIV Natural History Study cohort participants without HBV infection at the time of HIV diagnosis were grouped by vaccination status, retrospectively followed from HIV diagnosis for incident HBV infection, and compared using Cox proportional hazards models. A positive vaccine response was defined as hepatitis B surface antibody level ≥10 IU/L. Of 1,877 participants enrolled between 1989 and 2008, 441 (23%) were vaccinated prior to HIV diagnosis. Eighty percent of those who received vaccine doses only before HIV diagnosis had a positive vaccine response, compared with 66% of those who received doses both before and after HIV and 41% of those who received doses only after HIV (P < 0.01 for both compared with persons vaccinated before HIV only). Compared with the unvaccinated, persons vaccinated only before HIV had reduced risk of HBV infection after HIV diagnosis (hazard ratio = 0.38, 95% confidence interval: 0.20, 0.75). No reduction in HBV infection risk was observed for other vaccination groups. These data suggest that completion of the vaccine series prior to HIV infection may be the optimal strategy for preventing this significant comorbid infection in HIV-infected persons.

Objective

To evaluate the incidence rates of anal cancer over the HIV epidemic and assess the impact of HAART use on anal cancer events.

Methods

We evaluated the incidence of and factors associated with anal cancer using longitudinal data from the prospective U.S. Natural History Study (1985-2008). Poisson regression and Cox proportional hazard models were utilized.

Results

Among 4,506 HIV-infected males with 37,806 person-years (PY) of follow-up, anal cancer rates (per 100,000 PY) increased 5-fold, from 11 in the pre-HAART to 55 in the HAART era, p=0.02. Rates continued to increase, reaching 128 in 2006-2008. Persons with HIV infection for >15 years had a 12-fold higher rate than those with <5 years (348 vs. 28, p<0.01). At cancer diagnosis (n=19), median age was 42 years, median CD4 count was 432 cells/mm3, 74% had a CD4 nadir <200 cells/mm3, 42% had a prior AIDS event, and 74% had received HAART. From separate models, prior AIDS event (HR 3.88, p=0.01) and lower CD4 nadir (HR 0.85 per 50 cell, p=0.03) were associated with anal cancer, with a trend for a history of gonorrhea (HR 2.43, p=0.07). Duration of HAART use was not associated with a reduced risk of anal cancer (HR 0.94, p=0.42).

Conclusions

Incidence rates of anal cancer have progressively increased during the HIV epidemic. Persons with a longer duration of HIV infection have a substantially higher rate of anal cancer. Since HIV-infected persons are experiencing longer life expectancies and HAART does not appear protective of anal cancer, studies on preventive strategies are needed.

The influence of highly active antiretroviral therapy (HAART) upon hepatitis B virus (HBV) vaccine responses in HIV-infected individuals is unclear. After classification of vaccinees as non-responders (HBsAb <10 IU/L) or responders (HBsAb ≥10 IU/L) in our HIV cohort, multivariate logistic regression was used to assess factors associated with subsequent vaccine response. Of 626 participants vaccinated from 1988–2005, 217 (35%) were vaccine responders. Receipt of ≥3 doses of vaccine (OR 1.83, 95% CI 1.24–2.70), higher CD4 count at vaccination (OR 1.09, 95% CI 1.05–1.13 per 50 cells/μl increase), and use of HAART (OR 2.37, 95% CI 1.56–3.62) were all associated with increased likelihood of developing a response. However, only 49% of those on HAART at last vaccination responded, and 62% of those on HAART, with CD4 count ≥350, and HIV RNA <400 copies/mL responded. Compared to those on HAART with CD4 count ≥350, those not on HAART with CD4 count ≥350 had significantly reduced odds of developing a vaccine response (OR 0.47, 95% CI 0.30–0.70). While HAART use concurrent with HBV immunization was associated with increased probability of responding to the vaccine, the response rate was low for those on HAART. These data provide additional evidence of HAART benefits, even in those with higher CD4 counts, but also highlight the need for improving HBV vaccine immunogenicity.

Background

Preclinical studies suggest that the antiretroviral agent, nelfinavir mesylate (NFV), may have antineoplastic properties. The relationship between NFV and cancer incidence among HIV-infected patients is unknown.

Methods

We evaluated the impact of NFV on cancer development in a large cohort of HIV-infected persons with 108 cancer events during 13,421 person-years of follow-up. Using multivariate time-updated Cox proportional hazard models, the risk of cancer among those receiving NFV were compared to those on non-NFV antiretroviral regimens.

Results

The risk of cancer among those receiving NFV was similar to those on non-NFV antiretroviral regimens (hazard ratio 1.0, 95% confidence interval 0.5, 1.7, P=0.90). We also examined AIDS-defining and non-AIDS-defining cancers separately and found no significant associations between NFV use and cancer risk. Antiretroviral use, with or without a protease inhibitor (PI) component, was associated with a reduced risk of AIDS-defining cancers compared with no antiretroviral therapy; however, the risk of cancer was the same among those using PI or PI-sparing regimens.

Discussion

Despite reports that NFV may have tumoricidal activity, we found no significant relationship between NFV or PI use compared with other antiretrovirals and the risk of developing cancer among a large cohort of HIV-infected persons. Nelfinavir mesylate (NFV) is a protease inhibitor (PI) approved by the Food and Drug Administration (FDA) in March of 1997 and widely used as a component of early antiretroviral regimens. Recently, NFV has been evaluated for potential repositioning as part of cancer therapy (1). PI side effects, such as insulin resistance and hyperlipidemia, were noted to be similar to those observed from the blockade of phosphoinositide 3-kinase/Akt, a known survival pathway for cancer cells (2). Recent data suggest that PIs, particularly NFV, inhibit tumor growth via Akt inhibition (1) as well as by other mechanisms.

Background

As life expectancy of HIV-infected persons increases, cancers have become an important cause of morbidity and mortality. Although cutaneous neoplasms are the most common malignancies in the general population, little data exist among HIV-positive persons especially regarding the impact of HIV-specific factors.

Methods

We evaluated the incidence rates and factors associated with the development of cutaneous malignancies among HIV-infected persons by examining prospectively collected data from a large HIV Natural History Study composed of 4,490 persons (1986 to 2006). Poisson regression and Cox proportional hazards models were performed.

Results

Six percent (n=254) of HIV-infected persons developed a cutaneous malignancy during 33,760 person-years of follow-up (mean 7.5 years). Since the advent of highly active antiretroviral therapy (HAART), incidence rates of cutaneous non-AIDS defining cancers (NADCs), in particular basal cell carcinoma, have exceeded rates of cutaneous AIDS-defining cancers such as Kaposi’s sarcoma. Factors associated with the development of cutaneous NADCs in the multivariate models included increasing age (hazard ratio (HR) 2.1; 95% CI 1.7–2.6) and race. Compared to white/non-Hispanic race, African Americans (HR 0.03, 95% CI 0.01–0.14) and other races (HR 0.14, 95% CI 0.03, 0.57) had a lower risk of cutaneous NADCs. There were no significant associations between cutaneous NADCs and time-updated CD4 counts, HIV RNA levels, or HAART receipt.

Conclusions

NADCs are now the most common cutaneous malignancies among HIV-infected persons. Cutaneous NADCs do not appear to be significantly associated with immune function or HAART, but rather are related to traditional factors, such as aging and skin color.

Background

Whether HIV seroconverters are presenting with lower CD4 counts over the HIV epidemic is controversial. Additional data on whether HIV may have become more virulent on a population level, as measured by post-seroconversion CD4 counts, may provide important insights regarding HIV pathogenesis.

Methods

To determine if the post-seroconversion CD4 counts have changed over calendar time, we evaluated 2,174 HIV seroconverters as part of a large cohort study (1985-2007). Participants were documented HIV seroconverters who were antiretroviral naïve and had a CD4 count within six months of HIV diagnosis. Multiple linear regression models were used to assess trends in initial CD4 counts.

Results

The mean initial CD4 count decreased during the study period: 632 cells/mm3 in 1985-1990, 553 cells/mm3 in 1991-1995, 493 cells/mm3 in 1996-2001, and 514 cells/mm3 in 2002-2007. During the time periods, the percentage of seroconverters with an initial CD4 count of <350 cells/mm3 was 12%, 21%, 26%, and 25%, respectively. In the multiple linear model, the mean CD4 count in 1991-1995 was -65 cells/mm3 (p<0.0001), 1996-2001 was -107 cells/mm3 (p<0.0001), and 2002-2007 was -102 cells/mm3 (p<0.0001) compared to 1985-1990. Similar trends occurred in the CD4 percentage and total lymphocyte count. African-Americans and Whites had similar decreases in initial CD4 counts during the epidemic.

Discussion

A significant decline in initial CD4 counts among U.S. HIV seroconverters occurred during the epidemic. These data provide an important clinical correlate to studies suggesting that HIV may have adapted to the host resulting in a more virulent infection.

Objective

To describe trends in incidence rates of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) during the HIV epidemic and to evaluate predictors, including the impact of antiretroviral therapy, of cancer development.

Design

Retrospective analysis of a multicenter, prospective natural history study including 4,498 HIV-infected U.S. military beneficiaries with 33,486 person-years of follow-up.

Methods

Predictors evaluated included demographics, clinical data, time-updated CD4 cell counts, HIV viral loads, and antiretroviral history. Time periods were classified as early pre- (1984-1990), late pre- (1991-1995), early post- (1996-2000), and late post-(2001-2006) HAART eras. Cox proportional hazard models were used to evaluate the association of specific factors with cancer.

Results

Ten percent of HIV-infected persons developed cancer. ADC rates increased between the early and late pre-HAART eras (7.6 and 14.2 cases per 1000 person years) and have since declined from 5.4 to 2.7 in the early and late HAART eras, respectively (p<0.001). Rates of NADCs have risen over the four time periods (2.9, 2.8, 4.2, 6.7, p=0.0004). During the late HAART era, 71% of cancers were NADCs. Predictors for ADCs included low CD4 cell count, non-cancer AIDS diagnosis, and lack of HAART. NADCs were predicted by increasing age, Caucasian race (due to skin cancers), and lack of HAART.

Conclusions

Although the rate of ADCs continues to fall, the rate of NADCs is rising and now accounts for the majority of cancers in HIV-infected persons. The development of NADCs is associated with increasing age among HIV patients. HAART is protective for both ADCs and NADCs.

Background

Few data are available in Afghanistan to shape national military force health practices, particularly with regard to sexually-transmitted infections (STIs). We measured prevalence and correlates of HIV, syphilis, herpes simplex 2 virus (HSV-2), and hepatitis C virus (HCV) among Afghan National Army (ANA) recruits.

Methods

A cross-sectional sample of male ANA recruits aged 18–35 years were randomly selected at the Kabul Military Training Center between February 2010 and January 2011. Participants completed an interviewer-administered questionnaire and serum-based rapid testing for syphilis and hepatitis C virus antibody on-site; HIV and HSV-2 screening, and confirmatory testing were performed off-site. Prevalence of each infection was calculated and logistic regression analysis performed to identify correlates.

Results

Of 5313 recruits approached, 4750 consented to participation. Participants had a mean age of 21.8 years (SD±3.8), 65.5% had lived outside Afghanistan, and 44.3% had no formal education. Few reported prior marijuana (16.3%), alcohol (5.3%), or opiate (3.4%) use. Of sexually active recruits (58.7%, N = 2786), 21.3% reported paying women for sex and 21.3% reported sex with males. Prevalence of HIV (0.063%, 95% CI: 0.013- 0.19), syphilis (0.65%, 95% CI: 0.44 – 0.93), and HCV (0.82%, 95% CI: 0.58 – 1.12) were quite low. Prevalence of HSV-2 was 3.03% (95% CI: 2.56 - 3.57), which was independently associated with age (Adjusted Odds Ratio (AOR) = 1.04, 95% CI: 1.00 - 1.09) and having a television (socioeconomic marker) (AOR = 1.46, 95% CI: 1.03 – 2.05).

Conclusion

Though prevalence of HIV, HCV, syphilis, and HSV-2 was low, sexual risk behaviors and intoxicant use were present among a substantial minority, indicating need for prevention programming. Formative work is needed to determine a culturally appropriate approach for prevention programming to reduce STI risk among Afghan National Army troops.

Background

The prevalence and factors associated with overweight/obesity among human immunodeficiency virus (HIV)-infected persons are unknown.

Methods

We evaluated prospective data from a U.S. Military HIV Natural History Study (1985–2004) consisting of early diagnosed patients. Statistics included multivariate linear regression and longitudinal linear mixed effects models.

Results

Of 1682 patients, 2% were underweight, 37% were overweight, and 9% were obese at HIV diagnosis. Multivariate predictors of a higher body mass index (BMI) at diagnosis included more recent year of HIV diagnosis, older age, African American race, and earlier HIV stage (all p<0.05). The majority of patients (62%) gained weight during HIV infection. Multivariate factors associated with a greater increase in BMI during HIV infection included more recent year of diagnosis, lower BMI at diagnosis, higher CD4 count, lower HIV RNA level, lack of AIDS diagnosis, and longer HIV duration (all p<0.05). Nucleoside agents were associated with less weight gain; other drug classes had no significant impact on weight change in the HAART era.

Conclusions

HIV-infected patients are increasingly overweight/obese at diagnosis and during HIV infection. Weight gain appears to reflect improved health status and mirror trends in the general population. Weight management programs may be important components of HIV care.