Insulin-Like Growth Factor Is Associated with Changes in Body Composition with Antiretroviral Therapy Initiation.

Growth hormone (GH)/insulin-like growth factor (IGF)-1 axis abnormalities have been associated with body composition changes among HIV-infected persons with wasting or lipodystrophy. Little is known of GH/IGF-1 axis alterations with antiretroviral therapy (ART) initiation or differing ART therapies. The AIDS Clinical Trials Group Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study was a prospective, randomized clinical trial of ART initiation with emtricitabine/tenofovir + efavirenz (FTC/TDF+EFV) versus lamivudine/zidovudine + efavirenz (3TC/ZDV+EFV) in HIV-1-infected individuals from resource-diverse settings. IGF-1 was measured from baseline, week 48, and week 96 stored serum samples. Multivariate models were constructed. 415 participants were included: 170 (41%) were randomized to FTC/TDF+EFV and 245 (59%) to 3TC/ZDV+EFV. The mean age was 35 years, 60% were black, 42% women. The mean IGF-1 level did not change significantly from baseline to week 96 (-0.65 ng/ml; 95% confidence interval (CI) -5.18-3.87), p = .78 and there were no differences by treatment arm at week 96, p = .74. Lower baseline IGF-1 was associated with age, non-white race, greater waist-hip ratio (WHR), low CD4 count, and lower baseline albumin (all p < .01) but not plasma HIV-1 RNA, body mass index, or treatment arm. Greater change in IGF-1 from baseline to 96 weeks was associated with female sex, smaller WHR change, lower baseline albumin, and higher baseline HIV-1 RNA (all p < .01). ART initiation with either ZDV or TDF did not significantly impact overall IGF-1 levels. Baseline and on-treatment changes in IGF-1 with ART initiation may be related to the body composition changes that occur after ART initiation.

Rapid Multiplexed Immunoassay for Detection of Antibodies to Kaposi's Sarcoma-Associated Herpesvirus.

Diagnosis of KSHV-infected individuals remains a challenge. KSHV prevalence is high in several populations with high prevalence of HIV, leading to increased risk of development of Kaposi's sarcoma (KS). While current assays are reliable for detecting antibodies to KSHV, none are routinely utilized to identify individuals with KSHV infection and thus at increased risk for KS due to assay complexity, lack of access to testing, and cost, particularly in resource-limited settings. Here we describe the addition of KSHV proteins LANA and K8.1 to a previously evaluated HIV/co-infection multiplexed fluorescence immunoassay system. This study demonstrates assay performance by measuring antibody reactivity for KSHV and HIV-1 in a collection of clinical specimens from patients with biopsy-proven KS and sourced negative controls. The KSHV assay correctly identified 155 of 164 plasma samples from patients with biopsy-proven KS and 85 of 93 KSHV antibody (Ab)-negative samples for a sensitivity of 95.1% and specificity of 91.4%. Assay performance for HIV-1 detection was also assessed with 100% agreement with independently verified HIV-1 Ab-positive and Ab-negative samples. These results demonstrate good sensitivity and specificity for detection of antibody to KSHV antigens, and demonstrate the potential for multiplexed co-infection testing in resource-limited settings to identify those at increased risk for HIV-1-related complications.

Establishment of biochemistry reference values for healthy Tanzanian infants, children and adolescents in Kilimanjaro Region.

OBJECTIVE: To establish common biochemistry reference intervals for Tanzanian infants, children and adolescents living in the Kilimanjaro Region. METHODS: We recruited healthy, HIV-uninfected Tanzanian infants, children and youth between the ages of 1 month and 17 years from local schools and clinics to participate in this study. Only afebrile children without signs of physical or chronic illness were enrolled. Nonparametric methods were used to determine 95% reference limits and their 90% confidence intervals, with outliers removed by the Tukey method. RESULTS: A total of 619 healthy infants, children and adolescents were enrolled into the study. Twenty-three biochemistry parameters were measured. Compared to US reference intervals, several of the biochemistry parameters showed notable differences, namely alkaline phosphatase, phosphorus, amylase and lipase. Comparing our data to the US National Institutes of Health (NIH) Division of AIDS (DAIDS) grading criteria for classification of adverse events, we found that for selected parameters, up to 15% of infants or children in certain age groups would have been categorised as having an adverse event as defined by DAIDS. CONCLUSIONS: Our study further confirms the need to use locally established reference intervals to define reference laboratory parameters among children in Africa, rather than relying on those derived from US or European populations. To our knowledge, this study provides the first set of locally validated biochemistry reference ranges for a paediatric population in Tanzania.

Seroprevalence of Hepatitis B and C Viruses Among Children in Kilimanjaro Region, Tanzania.

BACKGROUND: Data on human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection among children in Africa are limited. We evaluated the seroprevalence of both viruses among healthy, HIV-uninfected children and HIV-infected children in the Kilimanjaro region of northern Tanzania. METHODS: HBV and HCV markers were assessed using serum and plasma samples from HIV-negative children ages 1 month to 18 years, recruited primarily from 2 hospital vaccination clinics; and HIV-infected children 1-16 years of age, enrolled in care and on highly active antiretroviral therapy (HAART). HBV markers included hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (HBcAb). Evidence of any prior HBV infection was defined as a single positive HBsAg or HBcAb result; presumed chronic hepatitis B infection was defined as a single positive HBsAg result. HCV infection was assessed by anti-HCV enzyme-linked immunosorbent assay. RESULTS: Samples from 547 children were tested. Of 157 children infected with HIV, 9.6% (95% CI: 4.9, 14.2) showed evidence of any HBV infection, compared to 2.1% (95% CI: .6, 3.5) of HIV-negative children. Children with HIV were much more likely to show evidence of HBV infection than children without HIV (odds ratio [OR] = 5.0, P < .0001). Prevalence of presumed chronic HBV infection was 2.9% (95% CI: 1.5, 4.3) overall. Again, prevalence was higher among HIV-infected children (7.0% [95% CI: 3.0, 11.0]) compared to HIV-negative children (1.3% [95% CI: .2, 2.4]; OR = 5.8 [P = .0003]). Of 546 samples tested for anti-HCV antibody, none were positive. CONCLUSION: HBV seroprevalence is high among children in the Kilimanjaro Region, with a significantly higher prevalence among children who are infected with HIV. Routine screening for HBV is needed among HIV-infected children. Patients with coinfection require closer monitoring of liver transaminases due to potential for hepatic toxicities, and they may need HAART regimens that will target both viruses. Guidelines for the management of coinfected children are urgently needed.

Changes in HIV risk behavior and seroincidence among clients presenting for repeat HIV counseling and testing in Moshi, Tanzania.

While HIV counseling and testing (HCT) has been considered an HIV preventive measure in Africa, data are limited describing behavior changes following HCT. This study evaluated behavior changes and estimated HIV seroincidence rate among returning HCT clients. Repeat and one-time testing clients receiving HCT services in Moshi, Tanzania were identified. Information about sociodemographic characteristics, HIV-related behaviors and testing reasons were collected, along with HIV serostatus. Six thousand seven hundred and twenty-seven clients presented at least once for HCT; 1235 (18.4%) were HIV seropositive, median age was 29.7 years and 3712 (55.3%) were women. 1382 repeat and 4272 one-time testers were identified. Repeat testers were more likely to be male, older, married, or widowed, and testing because of unfaithful partner or new sexual partner. One-time testers were more likely to be students and testing due to illness. At second test, repeat testers were more likely to report that partners had received HIV testing, not have concurrent partners, not suspect partners have HIV, and have partners who did not have other partners. Clients who intended to change behaviors after the first test were more likely to report having changed behaviors by remaining abstinent (OR 2.58; p<0.0001) or using condoms (OR 2.00; p=0.006) at the second test. HIV seroincidence rate was 1.49 cases/100 person-years (PY). Clients presenting for repeat HCT reported some reduction of risky behavior and improved knowledge of sexual practices and HIV serostatus of their partners. Promoting behavior change through HCT should continue to be a focus of HIV prevention efforts in sub-Saharan Africa.