Journal of AIDS & Clinical Research

CD4+ T cell depletion and immune activation are hallmarks of HIV infection. Despite extensive studies, the mechanisms underlying immune modulation remain elusive. HIV-1 Nef protein is secreted in exosomes from infected cells and is abundant in the plasma of HIV+ individuals. Exosomal Nef (exNef) was also shown to induce apoptosis in bystander CD4+ T cells. We hypothesized that exNef contributes to HIV pathogenesis. A HIV-1 NL4-3 virus containing alanine substitutions in the secretion modification region (SMR; amino acids 66 to 70; HIVNefsmr5a) was developed. Nef protein containing this modified SMR was shown to be deficient in exNef secretion in nef-transfected cells. Using both HIV-1 NL4-3 wild type (HIVwt) and HIVNefsmr5a, correlates of pathogenesis were evaluated in cell-lines, human peripheral blood mononuclear cells, and humanized NOD-RAG1 -/- IL2r -/- double mutant (NRG) mice. Disruption of the SMR did not affect viral replication or exNef secretion from infected cell cultures as compared with nef-transfected cells. However, T cell apoptosis was reduced in HIVNefsmr5a infected cell cultures and CD4+ T cell depletion was reduced in the spleen and peripheral blood of similarly infected NRG mice. Inflammatory cytokine release was also decreased in the sera of HIVNefsmr5a infected mice relative to HIVwt infected controls. These findings demonstrate the importance of Nef and the SMR motif in HIV pathogenesis and suggest a potential role for exNef in HIV-driven immune modulation

Background: HIV-infected Asians may be at risk for tenofovir toxicity due to their relatively low body weight (BW). We assessed the prevalence of proximal tubular dysfunction (PRTD) and risk associated with PRTD in HIV-infected adults receiving tenofovir in Thailand.

Methods: A cross-sectional study in HIV-infected adults (≥ 18years) treated with tenofovir for >1 year. Twenty-fourhour urine samples were collected to assess PRTD. PRTD was defined as the presence of >2 of the following criteria: hyper-phosphaturia (total excretion of phosphate >1200 mg/day or renal tubular reabsorption of phosphate (TmP/ GFR) < 2.6 mg/dl), hyper-uricosuria (FE of uric acid >15%), or non-diabetic glucosuria. Mid-dose tenofovir plasma concentrations were determined and concentrations >160 ng/mL were used as a cut-off for assessing risk of PRTD.

Results: 351 subjects (52% males) with median age of 40.2 years, BW of 58.9 kg, and duration of tenofovir treatment 4.7 years were included. 93% had a HIV-1 RNA <50 copies/mL and 7% were co-infected with HCV. Fiftyfour (15.4%) patients were diagnosed with PRTD. In a multivariate analysis, only a mid-dose tenofovir concentration >160ng/mL was associated with PRTD [odds ratio: OR 2.02 (95% CI 1.13-3.66)]; 32 of 54 (59.2%) with PRTD had a tenofovir concentration >160 ng/ml; versus 124 of 297 patients (41.7%) without PRTD (p = 0.02). Predictors of a tenofovir concentration >160ng/mL were BW<55 kg [OR2.32 (95% CI 1.45-3.68)], chronic HCV [OR 2.64 (95% CI 1.13-6.17)], eGFR<90 mL/min/1.73m2 [OR 2.66 (95% CI 1.64-4.31)], lopinavir/ritonavir [OR 2.47 (95% CI 1.32-4.6)] and PRTD [OR 2.08(95% CI 1.10-3.92)].

Conclusion: Mid-dose tenofovir concentrations >160 ng/mL were independently associated with PRTD. Tubular function should be closely monitored in patients using tenofovir with BW<55 kg, lopinavir/ritonavir use, chronic hepatitis C, or low eGFR.

Background: Some studies have shown that greater perceived vulnerability to HIV is associated with less involvement in risk taking. We evaluated prevalence and correlates of HIV risk perception among men who have sex with men (MSM) in Nigeria.

Methods: A cross sectional study using respondent driven sampling (RDS) was conducted in six Nigerian states in 2010. Weighted HIV risk perceptions were calculated using an RDS analytic tool. Logistic regression was used to determine correlates of HIV risk perception, stratified by state.

Results: The total number of MSM ranged from 217 in Abuja to 314 in Cross River state. Median age ranged from 22 years in Cross River state to 26 years in Kano. HIV risk perception ranged from 10% in Cross River state to 58% in Kaduna state and was 38%, 44%, 19% and 20% in Kano, Lagos, Abuja and Oyo states respectively. Factors associated with HIV risk perception include purchasing sex (AOR: 3.11, 95% CI: 1.09-8.88) and never being tested for HIV (AOR = 0.34, 95% CI: 0.14 - 0.85] in Cross River; no comprehensive knowledge of HIV (AOR = 0.21, 95% CI: 0.05 - 0.90) and receptive anal partners (AOR = 10.07, 95% CI: 2.07 - 49.02) in Abuja; being older than 25 years (AOR = 0.16, 95% CI: 0.03 - 0.98) in Kano; no exposure to peer education in Kaduna (AOR = 0.08, 95% CI: 0.01 - 0.89); never being tested for HIV in Lagos (AOR = 0.11, 95% CI: 0.03 - 0.40) and Oyo state (AOR = 0.21, 95% CI: 0.06 - 0.80) and selling sex (AOR = 3.24, 95% CI: 1.00 - 10.61) in Oyo state.

Conclusion: This study shows that HIV risk perception and comprehensive HIV knowledge are very low among MSM in Nigeria. Heterogeneity in associated factors suggests that targeted interventions are needed to increase HIV risk perception in the different states. The role of HIV counseling and testing in increasing risk perception needs further evaluation.

Background: We measured antibody-dependent cell mediated cytotoxicity (ADCC) activity in serum and genital fluids of heterosexually exposed women during HIV seroconversion.

Methods: Plasma and cervico-vaginal lavage (CVL) fluid from 11 seroconverters (SC) were analyzed biannually from one year pre- to 6 year post-seroconversion using a 51Cr-release assay to measure HIV-1 gp120 specific ADCC.

Results: No SC had significant HIV specific CVL ADCC activity before seroconversion or until 1.5 yr after seroconversion. One individual had a %Specific Release (SR) of 25.4 at 2 years, 26.7 at 3 years and 21.0 at 4 years after seroconversion in CVL. Another sample had 4.7% SR at 2 years, 5.3 at 3 years, 10.9 at 4 years, and 8.4 at 5 years after seroconversion in CVL. A third had no activity until 17% SR 5 years after seroconversion in CVL. A fourth showed activity of 36.5% SR at 6.5 years after seroconversion. Seven women had no ADCC activity in their CVL. Paired serum samples showed HIV specific ADCC activity prior to the appearance of CVL ADCC activity.

Conclusions: HIV specific ADCC activity in CVL rose 2 years after seroconversion; ADCC was present in the serum prior to this time. These data suggest that genital tract ADCC activity is not present until well after acute infection.

Background: Treatment-related reductions in morbidity and mortality among human immunodeficiency virus (HIV)-positive patients have been attenuated by cigarette smoking, which increases risk of cardiovascular, respiratory, and neoplastic diseases. This study investigated factors associated with smoking status among HIV-positive patients.

Methods: This cross-sectional study included 2,464 HIV-positive patients attending the HIV Clinic at the University of Alabama at Birmingham between April 2008 and December 2013. Smoking status (current, former, never), psychosocial factors, and clinical characteristics were assessed. Multinomial logistic regression was used to obtain unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association of the various factors with smoking status.

Results: Among HIV-positive patients (mean age 45 years, 75% male, 55% African-American), the majority reported a history of smoking (39% current and 22% former smokers). In adjusted models, patient characteristics associated with increased odds of current smoking were male gender (OR for heterosexual men, 1.8 [95% CI: 1.3-2.6]; for men who have sex with men, 1.5 [1.1-1.9]), history of respiratory diseases (1.5 [1.2-1.9]), unsuppressed HIV viral load (>50 copies/mL) (1.5 [1.1-1.9]), depression (1.6 [1.3-2.0]), anxiety (1.6 [1.2-2.1]), and prior and current substance abuse (4.7 [3.6-6.1] and 8.3 [5.3-13.3] respectively). Male gender, anxiety, and substance abuse were also associated with being a former smoker.

Conclusions: Smoking was common among HIV-positive patients, with several psychosocial factors associated with current and former smoking. This suggests smoking cessation programs in HIV clinic settings may achieve greater impact by integrating interventions that also address illicit substance abuse and mental health.

Background: Prevention of mother to child transmission of HIV plays a major role in reducing the number of children being infected with HIV. This study provides baseline information about the knowledge, practice and factors that affect PMTCT service provision by traditional birth attendants.

Methods: A cross-sectional study of 142 traditional birth attendants in Ogun State, Nigeria carried out between January and March, 2014. Sample selection was by two-staged probability sampling technique. Data collection employed structured pre-tested questionnaires. Data were analysed using SPSS software for Windows (version 18). Uni-variate, bi-variate and multivariate analyses were done.

Results: Participants were universally aware of HIV. Participants’ ability to correctly identify temporal mode of MTCT of HIV varied from 69.0% for ante-partum; and 76.1% during labour and delivery to 60.6% during breastfeeding. Most of them (81.7%) knew that MTCT of HIV is preventable. Most of them knew that knowledge of HIV status (94.4%); and HCT (98.6%) were important for pregnant women. The mean score for knowledge of MTCT and PMTCT of HIV was 16.89 ± 1.89. Participants with secondary education or more (AOR = 3.020, 95%, CI = 1.362-6.697) were likely to know more about MTCT and PMTCT of HIV. Majority (88.7%) of the TBAs always offer HCT to pregnant women; 122 (85.9%) always refer HIV-positive women to treatment centres; and 126 (88.7%) always provide referral support for patients. The mean score for PMTCT care practice for the participants was high (45.85 ± 9.48).

Conclusion: TBAs have a role to play in the e-MTCT of HIV in Nigeria and are poised to do so. They have some knowledge and good practices as it relates to MTCT and PMTCT of HIV. Some misconceptions and bad practices exist especially as it relates to infant feeding practices. These need to be comprehensively addressed.

Development indicates maturation of functions; it is a continuous process starting in utero and progresses in an orderly manner until maturity. Both growth and development are closely related hence factors affecting one, also tend to affect the other. The Central Statistical Office’s Living Conditions Survey of 2010 in Zambia indicated that amongst children aged between 3 to 59 months which is just under 6 years 48.3% of the children in the rural areas of Zambia were stunted and 42.3% were stunted in the urban areas with an average stunted rate of 46.7% overall in the whole country. The first 24 months of life technically denotes the infancy period. It is a time when a child’s brain undergoes rapid development. During this phase, a child attains several milestones relating to motor, cognitive and behavioral development. This is a very sensitive period whereby any slight disruption to the process can negatively result into growth failure in terms of both motor and cognitive development. HIV has been linked to a wide range of developmental challenges such as cognitive development stagnation, neurological problems, learning difficulties and speech and language problems. Though it is difficult to isolate its singular effect on the neurological status of children infected with it, research has established that 90% of the HIV positive children have neurological problems. HIV is a serious health concern in Zambia, this paper highlights literature in this area and discusses the impact of HIV on the developmental milestones of children and makes a comparison to the developmental milestones of children who are HIV negative.

Introduction: Hispanic adolescents domiciling in Florida rank second in the U.S. with respect to HIV/AIDS incidence and prevalence. Extending studies showing that risky sexual behavior is associated with limited access to information, this project surveyed knowledge about HIV etiology, prevention and treatment.

Methods: The sample consisted of 400 Hispanic youth between 11-18 years of age living in Miami, Florida. The sample is enrolled in an ongoing project Role of Brain Derived Neurotrophic Factor in Decision Making (ROBIM). The HIV Knowledge Questionnaire (HIV-KQ-18), an 18 item self-administered questionnaire was used to measure HIV knowledge, particularly transmission and prevention.

Results: Less than 10% of the sample had comprehensive knowledge about HIV/AIDS. Approximately 25% incorrectly answered all of the questions. Questions pertaining to transmission were incorrectly answered by more than half of the sample. The most frequent topics reflecting absence of knowledge are related to high-risk sexual behaviors (sex during the menses) and infection prevention methods (e.g. condoms). A majority of youth believed incorrectly that HIV could be cured (61%), an effective vaccine is available (61%), and antibiotics protect against HIV infection (76%). School (28%) and parents (26%) were the most frequent sources of knowledge about HIV/AIDS. However, youth receiving information from parents had significantly higher knowledge scores than peers receiving education in school (7.4 ± 4.15 vs. 6.1 ± 4.5 scores, p = 0.037). Yet, 68% of the sample had never discussed condom use with their parents.

Conclusions: These findings indicate Hispanic youths, although at very high risk, are poorly informed about prevention of HIV/AIDS. Moreover, the most frequent source of information, namely schools, inculcates less knowledge than parents. Lastly, youths who discuss sex with parents do not typically dialog about condoms, the most readily available protection from HIV/AIDS. These findings identify gaps that need to be addressed for lowering the high rate of HIV infection in Hispanic youths.

Background: Rapid HIV testing late in pregnancy or at delivery provides a final opportunity (among non-breastfeeding mothers) to identify HIV-infected women and initiate antiretroviral drugs to prevent mother-to-child transmission.

Methods: MIRIAD was a CDC-funded study conducted from 2001-2005 at 17 hospitals in 6 US cities. Eligible women had undocumented HIV status when presenting in labor or after 34 weeks gestation and not in labor. We performed both rapid HIV-1 antibody testing of blood and conventional enzyme immunoassay with Western blot confirmation. Women and infants were managed according to the local standard of care. Infant infection status was determined by HIV DNA or RNA PCR testing.

Results: Fifty-one infants (1 pair of twins) were born to 50 women. Among those with data available, 17% of women received prenatal antiretroviral and 71% received intrapartum antiretroviral, including 64% of those identified during labor. All 49 infants with available data received antiretroviral. Forty-four infants had adequate samples to determine their infection status and 5 were infected (11.4%, 95% CI: 1.9 - 20.7%); 3 had in utero, 1 intrapartum, and 1 indeterminate timing of transmission. No infant whose mother received prenatal antiretroviral was infected. The estimated rate of intrapartum transmission among infants with defined infection status was 4.5%.

Conclusions: Rapid HIV testing late in pregnancy or even during labor, allowing the administration of antiretroviral to infected women, reduces intrapartum HIV transmission. This highlights the importance of offering rapid HIV testing to pregnant women, with unknown HIV status late in pregnancy.

HIV-1 associated neuropathy remains an issue that interferes with patient’s quality of life. Distal Sensory Peripheral Neuropathy (DSPN) is the common neuropathy associated with HIV-1 infection. We studied the role of HIV-1 in developing DSPN in 157 HIV-positive patients. Our results pointed to the potential role of HIV-1 in the etiology of DSPN and pain syndrome.

Background: Migrant workers worldwide are at high risk of acquiring and transmitting HIV and sexually transmitted infections. Over the past decade Central Asia has experienced an increase in new HIV infections and migration and mobility within the region. These trends call for mixed methods research to explore the environmental and mobility contexts in which HIV risk behaviors occur among Central Asian migrants, particularly those in Kazakhstan, a common destination country.

Methods: This study took place in Almaty’s Baraholka Market, which employs 30,000 workers including many migrant workers from Central Asian countries. We used a convenience sampling approach to recruit 48 male migrant workers from Uzbekistan, Tajikistan, Kyrgyzstan, and Kazakhstan. Through in-depth interviews, we examined both their engagement in a number of sexual HIV risk behaviors (including having outside partners, sex trading, and condom use) as well as the meaning they attributed to such behaviors. We also address micro-social contexts (employment, types of relationships, infidelity, and access to resources), macro-contexts (gender roles and power dynamics) and structural contexts (mobility and policing) to examine how environmental influences influenced HIV risks.

Results: Findings suggest that men in this study attributed sex with extramarital partners to sexual desires when wives are unable to have sex, mobility and separation, need for variety, and lack of satisfaction in marriage. Factors influencing condom use included trust, sexual pleasure, intention to protect one’s health, and alcohol use. Participants had low levels of knowledge about HIV/AIDS; believed HIV did not affect their community or social networks, and had limited access to health care.

Conclusions: Study findings call for a combination of contextually sustainable HIV/STI prevention strategies that target migrant workers in Central Asia.