High-risk human papilloma virus and cervical abnormalities in HIV-infected women with normal cervical cytology

Background: The prevalence of High-Risk Human papilloma virus (HR-HPV), a necessary cause of invasive cervical cancer (ICC) is relatively high in HIV infected women. Gaps exist in our knowledge of the optimal approaches for managing women who have HR-HPV with normal cervical cytology (NCC) particularly in settings of HIV infection. Methods: Between May 2012 and June 2013 we conducted a colposcopic assessment of HIV-infected women with prior (NCC) and known HR-HPV status to compare cervical abnormalities in women with and without HR-HPV. Colposcopic examinations were done at the Operation Stop Cervical Cancer (OSCC) unit of the Jos University Teaching Hospital (JUTH), Jos, Nigeria. Abnormal colposcopic finding (ACF) was defined as areas of aceto-white epithelium involving the squamo-coulumnar junction, areas of punctation, mosaic pattern or atypical vessels. We compared proportions of ACF as well as histologic grades of cervical intra-epithelial neoplasia (CIN) in women with or without HR-HPV. Statistical analysis was done on STATA. Results: We conducted colposcopic examinations in 78 out of 89 (86.5%) eligible women. The mean age of the cohort was 32.4 years (SD ±4.6) with a median 32 years (IQR 29–36). After a mean follow up time of 20.1 months from the initial cervical pap cytology and HR-HPV testing, we found 12 of 78 (15.4%) women with ACF. The odds for an ACF was statistically higher [OR = 4.0 (95% CI: 1.1-14.7)] in women with HR-HPV compared to those without. Of the twelve women with ACF, subsequent histologic examination of colposcopically directed cervical biopsies confirmed CIN 1 in 4 cases (33.3%), CIN 2 in 1 case (8.3%), CIN 3 in 2 cases (16.7%), carcinoma-in-situ (CIS) in 2 cases (16.7%), and normal cervix in 3 (25.0%). Overall, the proportion of women detected with any grade of CIN was 11.5% (9/78) and 6.4% (5/78) were CIN 2 or greater lesion (CIN2+). Conclusion: HIV-infected women with NCC and HR-HPV had a four-fold higher likelihood for an ACF. The practice of early colposcopic examination of HIV-infected women with prior NCC and HR-HPV may increase early detection of higher grade CIN and CIS cancer stages in our setting

Treatment Outcomes in a Decentralized Antiretroviral Therapy Program: A Comparison of Two Levels of Care in North Central Nigeria

Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care

Association of Bacterial vaginosis and other Sexually Transmitted Infections with HIV among pregnant women in Nigeria.

OBJECTIVES: To determine the association of Bacterial vaginosis (BV) and other sexually transmissible infections (STIs) with HIV prevalence among pregnant women in Jos, Nigeria. METHODS: This was a cross- sectional study of pregnant women who participated in the Prevention of Mother-to-Child Transmission of HIV program of the AIDS Prevention Initiative in Nigeria, between April 2002 and July 2004, at the Jos University Teaching Hospital in Jos, Nigeria. Blood, high vaginal and endocervical samples were obtained for diagnosis of HIV, BV and other STIs. Data were analyzed for prevalence of HIV, BV and other STIs. Univariate and multivariate logistic regression models generated unadjusted and adjusted odds ratios (OR) as well as 95% confidence intervals (CI) of the association of BV and other STIs with HIV prevalence. P value <0.05 was considered statistically significant. RESULTS: A total of 4,046 pregnant women were studied and 97.6% (3,950/4,046) had complete laboratory records for analysis. The prevalence of HIV was 8.2% (CI: 7.4-9.1); BV 11.9% (CI: 10.9-12.9); Candida 10.7% (CI: 9.7-11.7); mixed infection of BV and Candida 2.8% (CI: 2.3-3.4); Trichomonads 0.6% (CI: 0.3-0.8) and syphilis 0.35% (0.16-0.54). BV, Candida, mixed BV and Candida; and Trichomonads were independently associated with HIV infection [adjusted OR (95% CI), 2.9 (CI: 2.2-3.9); 2.0 (CI: 1.5-2.9); 3.4 (CI: 2.0-5.6), and 3.3 (CI: 1.1-9.7) respectively]. CONCLUSION: HIV prevalence is higher among pregnant women who have BV, Candida and Trichomonads vaginal infections compared with women who have no evidence of infection. The practice of routine screening for BV and other STIs among pregnant women as a strategy for identifying women at risk for prevalent HIV infection should be sustained/ encouraged and the syndromic management of STIs should be integrated into all antenatal care management protocols in antenatal clinics in order to curb the epidemic of heterosexual HIV transmission

Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria

Background: To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations. Methods and Findings: From 2004–2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for 24 months. Patients developed a median of 0.6 (IQR: 0–1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir. Conclusions: This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access

Technology in Massachusetts Schools, 2004-2005

BACKGROUND:ATCC HIV-1 drug resistance test kit was designed to detect HIV-1 drug resistance (HIVDR) mutations in the protease and reverse transcriptase genes for all HIV-1 group M subtypes and circulating recombinant forms. The test has been validated for both plasma and dried blood spot specimen types with viral load (VL) of ≥1000 copies/ml. We performed an in-country assessment on the kit to determine the genotyping sensitivity and its accuracy in detecting HIVDR mutations using plasma samples stored under suboptimal conditions. METHODS:Among 572 samples with VL ≥1000 copies/ml that had been genotyped by ViroSeq assay, 183 were randomly selected, including 85 successful genotyped and 98 unsuccessful genotyped samples. They were tested with ATCC kits following the manufacturer's instructions. Sequence identity and HIVDR patterns were analysed with Stanford University HIV Drug Resistance HIVdb program. RESULTS:Of the 183 samples, 127 (69.4%) were successfully genotyped by either method. While ViroSeq system genotyped 85/183 (46.5%) with median VL of 32,971 (IQR: 11,150-96,506) copies/ml, ATCC genotyped 115/183 (62.8%) samples with median VL of 23,068 (IQR: 7,397-86,086) copies/ml. Of the 98 unsuccessful genotyped samples with ViroSeq assay, 42 (42.9%) samples with lower median VL of 13,906 (IQR: 6,122-72,329) copies/ml were successfully genotyped using ATCC. Sequence identity analysis revealed that the sequences generated by both methods were >98% identical and yielded similar HIVDR profiles at individual patient level. CONCLUSION:This study confirms that ATCC kit showed greater sensitivity in genotyping plasma samples stored in suboptimal conditions experiencing frequent and prolonged power outage. Thus, it is more sensitive particularly for subtypes A and A/G HIV-1 in resource-limited settings

Association of HIV-induced immunosuppression and clinical malaria in Nigerian adults

Background: Despite the growing body of evidence on the interaction between HIV and malaria in sub-Saharan Africa, there is a dearth of data on clinical malaria in HIV-infected patients in Nigeria. We determined the burden of clinical malaria in HIV-infected adult Nigerians and further investigated the association between their immunological status and the rates of clinical malaria. Methods: Ninety seven antiretroviral treatment-naïve HIV-infected adults were enrolled in a cross-sectional study from August to December, 2009. The participants had a complete clinical evaluation, thick and thin blood films for malaria parasites and CD4 cell count quantification. Clinical malaria was defined as having fever (temperature ≥ 37.5oC or history of fever within 48 hours) and a malaria parasite density above the median value obtained for subjects with co-existing fever and parasitaemia. Results: Clinical malaria was diagnosed in 10 out of 97 patients (10.3%). Lower CD4 cell counts were associated with increasing rates of clinical malaria which was 0% at CD4 cell count of ≥ 500, 2.6% at 200-499 and 30% a

Hepatitis B Co-Infection is Associated with Poorer Survival of HIV-Infected Patients on Highly Active Antiretroviral Therapy in West Africa

Background: Hepatitis B has been reported to be high in HIV-infected African populations. However, the impact of this co-infection on the survival of HIV-infected Africans on long-term highly active antiretroviral therapy (HAART) remains poorly characterised. We investigated the impact of HBV/HIV co-infection on survival of HIV infected patients undergoing antiretroviral therapy in a West African population. Methods: This was a clinic-based cohort study of HIV-infected adults enrolled in Nigeria, West Africa. Study subjects (9,758) were screened for hepatitis B and hepatitis C at HAART initiation. Kaplan-Meier survival and Cox proportional hazards models were used to estimate probability of survival and to identify predictors of mortality respectively, based on hepatitis B surface antigen status. All patients had signed an informed written consent before enrolment into the study; and we additionally obtained permission for secondary use of data from the Harvard institutional review board. Results: Patients were followed up for a median of 41 months (interquartile range: 30–62 months) during which, 181 (1.9%) patients died. Most of the deaths; 143 (79.0%) occurred prior to availability of Tenofovir. Among those that were on antiretroviral therapy, hepatitis B co-infected patients experienced a significantly lower survival than HIV mono-infected patients at 74 months of follow up (94% vs. 97%; p=0.0097). Generally, hepatitis B co-infection: HBsAg-positive/HIV-positive (Hazards Rate [HR]; 1.5: 95% CI 1.09–2.11), co-morbid tuberculosis (HR; 2.2: 95% CI 1.57–2.96) and male gender (HR; 1.5: 95% CI 1.08–2.00) were significantly predictive of mortality. Categorising the patients based on use of Tenofovir, HBV infection failed to become a predictor of mortality among those on Tenofovir-containing HAART. Conclusions: HBsAg-positive status was associated with reduced survival and was an independent predictor of mortality in this African HIV cohort on HAART. However, Tenofovir annulled the impact of HBV on mortality of HIV patients in the present study cohort

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age

<p>Abstract</p> <p>Background</p> <p>In <it>Plasmodium falciparum</it>-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults.</p> <p>Methods</p> <p>Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay.</p> <p>Results</p> <p>The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment.</p> <p>Conclusion</p> <p>The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.</p