Background Measuring progress towards the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90–90–90 treatment targets is key to assessing progress towards turning the HIV epidemic tide. In 2017, the UNAIDS model estimated that 75% of people living with HIV (PLHIV) globally knew their HIV positive status, 79% of those who knew their status were on antiretroviral therapy (ART), and 81% of those who knew their HIV status and were on ART had a suppressed viral load. The fifth South African national HIV sero-behavioural survey collected nationally representative data that enabled the empirical estimation of these 90–90–90 targets for the country stratified by a variety of key factors. Methods To evaluate progress towards achievement of the 90–90–90 targets for South Africa, data obtained from a national, representative, cross-sectional population-based multi-stage stratified cluster random survey conducted in 2017 were analysed. The Fifth South African National HIV Prevalence, Incidence, Behaviour and Communication Survey (SABSSM V), collected behavioural and biomarker data from individuals residing in households from 1000 randomly selected Small Area Layers (SALs), across all nine provinces of the country. Structured questionnaires were used to collect socio-demographic data, knowledge and perceptions about HIV, and related risk behaviours. Blood samples were collected to test for HIV infection, antiretroviral use, and viral suppression (defined as < 1000 copies/ml). Weighted proportions of study participants aged 15 years and older who tested HIV positive were computed for those who reported awareness of their status (1st 90), and among these, those who were currently on ART (2nd 90) and of these, those who were virally suppressed (3rd 90). Results Among persons 15 years and older who were HIV positive, 84.8% were aware of their HIV positive status, of whom 70.7% were currently on ART, with 87.4% of these estimated to have suppressed viral load at the time of the survey. These estimates varied by sex, age, and geo-location type. Relatively higher percentages across all three indicators for women compared to men were observed: 88.7% versus 78.2% for those aware of their status, 72.3% versus 67.7% for on ART, and 89.8% versus 82.3% for viral suppression. Knowing one’s positive HIV status increased with age: 74.0, 85.8, and 88.1% for age groups 15–24 years old, 25–49 years old and 50–64 years old, although for those 65 years and older, 78.7% knew their HIV positive status. A similar pattern was observed for the 2nd 90, among those who knew their HIV positive status, 51.7% of 15 to 24 year olds, 70.5% of those aged 25–49 years old, 82.9% of those aged 50–64 years old and 82.4% of those aged 65 years or older were currently on ART. Viral suppression for the above mentioned aged groups, among those who were on ART was 85.2, 87.2, 89.5, and 84.6% respectively. The 90–90–90 indicators for urban areas were 87.7, 66.5, and 87.2%, for rural settings was 85.8, 79.8, and 88.4%, while in commercial farming communities it was 56.2, 67.6 and 81.4%. Conclusions South Africa appears to be on track to achieve the first 90 indicator by 2020. However, it is behind on the second 90 indicator with ART coverage that was ~ 20-percentage points below the target among people who knew their HIV status, this indicates deficiencies around linkage to and retention on ART. Overall viral suppression among those on ART is approaching the target at 87.4%, but this must be interpreted in the context of low reported ART coverage as well as with variation by age and sex. Targeted diagnosis, awareness, and treatment programs for men, young people aged 15–24 years old, people who reside in farming communities, and in specific provinces are needed. More nuanced 90–90–90 estimates within provinces, specifically looking at more granular sub-national level (e.g. districts), are needed to identify gaps in specific regions and to inform provincial interventions.

Cancer cells have abnormal cell cycle regulation which favors accelerated proliferation, chromosomal instability, and resistance to the senescence response. Although the p16INK4a locus is the most prominent susceptibility locus for familial melanomas, the low frequency of p16 mutations in sporadic melanomas suggests additional alterations in other cell cycle regulatory genes. Here we used primary melanoma tumors to reveal early cell cycle alterations that could be masked in advanced metastatic lesions due to their inherently high genetic instability. Unexpectedly, the cyclin-dependent kinase inhibitors p27KIP1 and/or p21Waf-1/SDI-1 were found to be expressed in 13 of 18 (72%) of the primary melanomas with a Breslow thickness greater than 0.076 mm. In general, p27 and/or p21 staining in the primary tumors correlated with low Ki-67 index. Importantly, most of the p21- and p27-positive tumors expressed high levels of cyclin D1 and cyclin E. In proliferating cells p27 is predominantly associated with cyclin D-CDK4 complexes, but does not inhibit the kinase activity, whereas in quiescent cells p27 is found associated with inactive CDK2 complexes. p27 was also expressed at high levels in proliferating primary melanomas in culture, and found to be associated with active cyclin E-CDK2 complexes containing high levels of cyclin E. It is thus likely that accumulation of cyclin E overcomes the potent inhibitory activity of p27 and p21 in CDK2 complexes. Of the primary melanomas with no indication of invasiveness, only three of 15 (20%) were positive for p27 and/or p21. We propose that high levels of p27 and p21 may confer upon melanoma tumors their characteristic resistance to conventional therapies. In turn, high levels of cyclins E and D1 may contribute to unlimited proliferation in primary melanomas that express the tumor suppressor p16INK4. J Invest Dermatol 113:1039-1046 1999

South Africa has the largest number of people living with HIV worldwide. South Africa has implemented five population-based HIV prevalence surveys since 2002 aimed at understanding the dynamics and the trends of the epidemic. This paper presents key findings from the fifth HIV prevalence, incidence, and behaviour survey conducted in 2017 following policy, programme, and epidemic change since the prior survey was conducted in 2012. A cross-sectional population-based household survey collected behavioural and biomedical data on all members of the eligible households. A total of 39,132 respondents from 11,776 households were eligible to participate, of whom 93.6% agreed to be interviewed, and 61.1% provided blood specimens. The provided blood specimens were used to determine HIV status, HIV incidence, viral load, exposure to antiretroviral treatment, and HIV drug resistance. Overall HIV incidence among persons aged 2 years and above was 0.48% which translates to an estimated 231,000 new infections in 2017. HIV prevalence was 14.0% translating to 7.9 million people living with HIV. Antiretroviral (ARV) exposure was 62.3%, with the lowest exposure among those aged 15 to 24 years (39.9%) with 10% lower ARV coverage among males compared to females. Viral suppression among those on treatment was high (87.3%), whilst HIV population viral load suppression was much lower (62.3%). In terms of risk behaviours, 13.6% of youth reported having had an early sexual debut (first sex before the age of 15 years), with more males reporting having done so (19.5%) than females (7.6%). Age-disparate relationships, defined as having a sexual partner 5+ years different from oneself,) among adolescents were more common among females (35.8%) than males (1.5%). Self-reported multiple sexual partnerships (MSPs), defined as having more than one sexual partner in the previous 12 months, were more commonly reported by males (25.5%) than females (9.0%). Condom use at last sexual encounter was highest among males than females. Three quarters (75.2%) of people reported they had ever been tested for HIV, with more females (79.3%) having had done so than males (70.9%). Two-thirds of respondents (66.8%) self-reported having tested for HIV in the past 12 months. Finally, 61.6% of males in the survey self-reported as having been circumcised, with circumcision being more common among youth aged 15–24 years (70.2%), Black Africans (68.9%), and those living in both rural informal (tribal) areas (65%) and urban areas (61.9%). Slightly more (51.2%) male circumcisions were reported to have occurred in a medical setting than in traditional settings (44.8%), with more young males aged 15–24 (62.6%) and men aged 25–49 (51.5%) reporting to have done so compared to most men aged 50 and older (57.1%) who reported that they had undergone circumcision in a traditional setting. The results of this survey show that strides have been made in controlling the HIV epidemic, especially in the reduction of HIV incidence, HIV testing, and treatment. Although condom use at last sex act remains unchanged, there continue to be some challenges with the lack of significant behaviour change as people, especially youth, continue to engage in risky behaviour and delay treatment initiation. Therefore, there is a need to develop or scale up targeted intervention programmes to increase HIV testing further and put more people living with HIV on treatment as well as prevent risky behaviours that put young people at risk of HIV infection.

Background HIV drug resistance (HIVDR) testing was included in the 2017 South African national HIV household survey. We describe the prevalence of HIVDR by drug class, age, sex and antiretroviral drugs (ARV) status. Methods Dried blood were spots tested for HIV, with Viral load (VL), exposure to ARVs and HIVDR testing among those HIV positive. HIVDR testing was conducted on samples with VL ≥1000 copies/ml using Next Generation Sequencing. Weighted percentages of HIVDR are reported. Results 697/1,105 (63%) of HIV positive samples were sequenced. HIVDR was detected in samples from 200 respondents (27.4% (95% confidence interval (CI) 22.8–32.6)). Among these 130 (18.9% (95% CI 14.8–23.8)), had resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) only, 63 (7.8% (95% CI 5.6–10.9)) resistance to NNRTIs and nucleoside reverse transcriptase inhibitors, and 3 (0.5% (95% CI 0.1–2.1)) resistance to protease inhibitors. Sixty-five (55.7% (95% CI 42.6–67.9) of ARV-positive samples had HIVDR compared to 112 (22.8% (95% CI 17.7–28.7)), in ARV-negative samples. HIVDR was found in 75.6% (95% CI 59.2–87.3), n = 27, samples from respondents who reported ARV use but tested ARV-negative, and in 15.3% (95% CI 6.3–32.8), n = 7, respondents who reported no ARV use and tested ARV-negative. There were no significant age and sex differences in HIVDR. Conclusion 27% of virally unsuppressed respondents had HIVDR, increasing to 75% among those who had discontinued ARV. Our findings support strengthening first-line ARV regimens by including drugs with a higher resistance barrier and treatment adherence strategies, and close monitoring of HIVDR.

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