Jintanat Ananworanich

Background: Increasing rates of non-AIDS defining illnesses, and in particular liver diseases, have been found after the initiation of highly active antiretroviral therapy. However, there is little evidence concerning the risk factors for and clinical characteristics of liver disease in antiretroviral (ARV)-treated HIV infection, in the absence of hepatitis B or C viral co-infection. Methods: A nested case–control study of HIV infected volunteers, matched by starting date of anti-retroviral treatment, was conducted in a Thai cohort studied from Nov 2002 - July 2012. Cases were defined as those subjects with an elevated alanine aminotransferase (ALT ≥ 40 IU/L) at two consecutive visits six months apart, while controls were defined as individuals who never demonstrated two consecutive elevated ALT results and had a normal ALT result (< 40 IU/L) at their last visit. Both groups had normal ALT levels prior to ARV initiation. Clinical demographics and risk factors for chronic hepatitis including HIV-related illness, ARV treatment and metabolic diseases were collected and analyzed. Conditional logistic regression was used to determine risk factors for chronic hepatitis in HIV infection. Results: A total of 124 matched pairs with HIV infection were followed over 3,195 person-years. The mean age (±SD) was 33.0 ± 7.3 years, with 41.1% of subjects being male. The incidence of chronic hepatitis was 5.4 per 100 person-years. The median time from initiation of ARV to chronic hepatitis was 1.3 years (IQR, 0.5-3.5). From univariate analysis; male sex, plasma HIV-1 RNA level > 5 log ₁₀ copies/ml, metabolic syndrome at baseline visit, high BMI > 23 kg/m², abnormal HDL cholesterol at time of ALT elevation and treatment experience with NNRTI plus boosted PI were selected (p value < 0.2) to the final model of multivariate analysis. Male sex had 3.1 times greater risk of chronic hepatitis than the females by multivariate analysis (adjusted OR, 95% CI: 3.1, 1.5-6.3, p =0.002). High BMI ≥ 23 kg/m² was also associated with 2.4 times greater risk of chronic hepatitis (adjusted OR, 95% CI: 2.4, 1.2-4.8, p = 0.01). Conclusions: Chronic hepatitis in ARV-treated HIV-infected patients is common and may lead to a major health care problem. Male sex and high BMI ≥ 23 kg/m² carry higher risks for developing chronic hepatitis in this study. Therefore, these patients should be closely monitored for long-term hepatotoxicity.

Fourth generation (4thG) immunoassay (IA) is becoming the standard HIV screening method but was not available when the Fiebig acute HIV infection (AHI) staging system was proposed. Here we evaluated AHI staging based on a 4thG IA (4thG staging). Screening for AHI was performed in real-time by pooled nucleic acid testing (NAT, n=48,828 samples) and sequential enzyme immunoassay (EIA, n=3,939 samples) identifying 63 subjects with non-reactive 2nd generation EIA (Fiebig stages I (n=25), II (n=7), III (n=29), IV (n=2)). The majority of samples tested (n=53) were subtype CRF_01AE (77%). NAT+ subjects were re-staged into three 4thG stages: stage 1 (n=20; 4th gen EIA-, 3rd gen EIA-), stage 2 (n=12; 4th gen EIA+, 3rd gen EIA-), stage 3 (n=31; 4th gen EIA+, 3rd gen EIA+, Western blot-/indeterminate). 4thG staging distinguishes groups of AHI subjects by time since presumed HIV exposure, pattern of CD8+ T, B and natural killer cell absolute numbers, and HIV RNA and DNA levels. This staging system further stratified Fiebig I subjects: 18 subjects in 4thG stage 1 had lower HIV RNA and DNA levels than 7 subjects in 4thG stage 2. Using 4th generation IA as part of AHI staging distinguishes groups of patients by time since exposure to HIV, lymphocyte numbers and HIV viral burden. It identifies two groups of Fiebig stage I subjects who display different levels of HIV RNA and DNA, which may have implication for HIV cure. 4th generation IA should be incorporated into AHI staging systems.

Despite the major advances in the management of HIV infection, HIV-infected patients still have greater morbidity and mortality than the general population. Serious non-AIDS events (SNAEs), including non-AIDS malignancies, cardiovascular events, renal and hepatic disease, bone disorders and neurocognitive impairment, have become the major causes of morbidity and mortality in the antiretroviral therapy (ART) era. SNAEs occur at the rate of 1 to 2 per 100 person-years of follow-up. The pathogenesis of SNAEs is multifactorial and includes the direct effect of HIV and associated immunodeficiency, underlying co-infections and co-morbidities, immune activation with associated inflammation and coagulopathy as well as ART toxicities. A number of novel strategies such as ART intensification, treatment of co-infection, the use of anti-inflammatory drugs and agents that reduce microbial translocation are currently being examined for their potential effects in reducing immune activation and SNAEs. However, currently, initiation of ART before advanced immunodeficiency, smoking cessation, optimisation of cardiovascular risk factors and treatment of HCV infection are most strongly linked with reduced risk of SNAEs or mortality. Clinicians should therefore focus their attention on addressing these issues prior to the availability of further data.

Background: The relationship between HIV serostatus disclosure and sexual risk behavior is inconsistent across studies. As men who have sex with men (MSM) are emerging as the key affected population in Bangkok, Thailand with reported HIV prevalence of 30%, we assessed whether HIV disclosure is associated with protected sex in this population. Methods: A risk behavior questionnaire was administered using Audio Computer-Assisted Self-Interviewing (ACASI) to determine whether HIV serostatus disclosure was associated with protected sex in 200 HIV-positive MSM in Bangkok. HIV serostatus disclosure to the most recent sexual partner prior to or at the time of the sexual encounter was assessed. Protected sex was defined as insertive or receptive anal intercourse with a condom at the most recent sexual encounter. Results: The mean age was 30.2 years, CD4 was 353 cells/mm³, and one-third was on antiretroviral therapy. At the most recent sexual encounter, HIV serostatus disclosure rate was low (26%); 60.5% of subjects had not discussed their serostatus at all, while 5.5% had not revealed their true serostatus. Seventeen percent reported unprotected anal intercourse and about half had sex with their primary partners. The serostatus of the most recent sexual partner was HIV-positive in 19.2%, HIV-negative in 26.4%, and unknown in 54.4% of subjects. There was no association between disclosure and protected sex, with 41 of 48 (85.4%) disclosers and 104 of 126 (82.5%) of non-disclosers reported protected sex (p = .65). Subjects with HIV-positive partners were less likely to report protected sex overall (20 of 33, 60.6%) compared to those with HIV negative (82 of 96, 85.4%) or unknown (41 of 45, 91.1%) partners (p = .001). Age (27-32 years vs. ≤26 years, p = .008), primary partner status (p < .001), and HIV-positive serostatus of sexual partner (p < .001) were significantly associated with disclosure in the multivariate analyses. Conclusion: Rates of HIV disclosure to sexual partners by HIV-positive MSM in Bangkok are low. Despite low rates of HIV serostatus disclosure, most HIV-positive MSM reported protected sex with their partners at risk for infection. Future studies should focus on understanding barriers to disclosure and factors driving risk behavior amongst MSM in Thailand.

Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy. We prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm³. HIV RNA was 5.5 log₁₀ copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/10⁶ PBMC) vs. Fiebig I (8 copy/10⁶ PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of <50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02). Gut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission.

Histoplasmosis and penicilliosis are fungal infections with similar clinical presentation and laboratory findings that were reported mainly in the era prior to highly active antiretroviral therapy. We conducted a retrospective review at two hospitals in Central Thailand of the medical records of HIV-positive patients with microbiologic evidence of histoplasmosis or penicilliosis between January 2003 to September 2007 when anti retrovirals became widely available in Thailand. Fifty patients met inclusion criteria; 36 had histoplasmosis, and 14 had penicilliosis. Symptoms and laboratory findings on presentation were similar between the two infections except for a greater incidence of tachypnea and neutropenia among patients with histoplasmosis (both p < 0.05). For histoplasmosis, blood culture had a significantly lower yield for detecting infection compared to tissue microscopic examination highlighting the importance of obtaining tissue for diagnosis (p < 0.05).

Sexual behavior of HIV-positive youths, whether infected perinatally, through risky behavior or other ways, is not substantially different from that of HIV-uninfected peers. Because of highly active antiretroviral therapy, increasing number of children, infected perinatally, are surviving into adolescence and are becoming sexually active and need reproductive health services. The objective of this article is to review the methods of contraception appropriate for HIV-positive adolescents with a special focus on hormonal contraceptives. Delaying the start of sexual life and the use of two methods thereafter, one of which is the male condom and the other a highly effective contraceptive method such as hormonal contraception or an intrauterine device, is currently the most effective option for those who desire simultaneous protection from both pregnancy and sexually transmitted diseases. Health care providers should be aware of the possible pharmacokinetic interactions between hormonal contraception and antiretrovirals. There is an urgent need for more information regarding metabolic outcomes of hormonal contraceptives, especially the effect of injectable progestins on bone metabolism, in HIV-positive adolescent girls.

Objective: The objective of this study was to investigate the incidence, demographics, HIV subtype, and genotypic resistance of acute HIV infections in a high-risk Thai population. Methods: Between March 2006 and September 2007, 6426 stored samples at the Thai Red Cross Anonymous Clinic were screened for acute HIV infection by 2 methods: pooled nucleic acid testing (NAT) of fourth-generation enzyme immunoassay (EIA)-negative samples (n = 5402) and subsequent first-generation EIA testing of fourth-generation EIA-positive samples (n = 1024). Results: Eleven acute HIV-infected subjects were identified by pooled NAT (n = 7) and serial EIA (n = 4). Mean age was 28 years; 9 were male; and 60% were men who have sex with men. Median HIV RNA was 99,601 copies per milliliter (log₁₀ viral load (VL) = 5.00). Eight samples could be genotyped: 6, CRF01_AE; 1, subtype B; and 1, CRF01_AE/B recombinant. No resistance to antiretroviral therapy was found. The HIV incidence per 100 person-years, calculated from the pooled, antibody-negative samples, was 2.7% (95% confidence interval, 2.2%-4.3%). Conclusions: This is the first report of antibody-negative, NAT-positive, acute HIV infection in Thailand. The majority were men who have sex with men, which reflects the current epidemic in Thailand and justifies prevention programs aimed at this group. This high-risk population may be suitable for future studies on acute HIV infection, HIV treatment, vaccine, and prevention of onward transmission strategies.

TO THE EDITOR—In Thailand, an estimated 20,000 children are living with HIV infection, at least one-half of whom have lost one or both parents. Caring for an HIV-infected child is complex, especially when there is a need to administer antiretroviral therapy (ART). Caregivers play a major role in assuring that children adhere to therapy. We investigated whether adherence to ART was different for Thai children with biological parents (BPs) versus nonbiological parents (NBPs).

Purpose of review The aim of this article is to present approaches towards simplifying pediatric antiretroviral therapy in order to improve access to care, coverage of HIV-positive children, and support adherence to treatment. Recent findings Barriers to rapid and effective global scale-up of pediatric antiretroviral therapy include the narrow range of available pediatric antiretrovirals, complicated dosing schedules, and social and economic instability of the family caused by poverty, stigma, and death. Healthcare providers can simplify antiretroviral therapy delivery by promoting the development and use of pediatric fixed dose combinations and scored adult antiretrovirals, using weight-band dosing tables to prescribe antiretrovirals, and identifying less complex regimens. Caretakers would benefit from active counseling to facilitate more open communication with their children about adherence and disclosure. Children can develop long-term coping strategies through learning life skills that build confidence and improve decision-making. Whenever possible, antiretroviral therapy programs should provide access to free antiretrovirals, identify funds to cover transportation costs, and refer families to available community support programs. Summary Interventions to simplify the administration of antiretroviral therapy need to address not only how antiretrovirals are prescribed and formulated, but the relationships of HIV-positive children with their families and communities as well.